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Sample records for evokes excitatory alterations

  1. Comparing the Efficacy of Excitatory Transcranial Stimulation Methods Measuring Motor Evoked Potentials

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    Vera Moliadze

    2014-01-01

    Full Text Available The common aim of transcranial stimulation methods is the induction or alterations of cortical excitability in a controlled way. Significant effects of each individual stimulation method have been published; however, conclusive direct comparisons of many of these methods are rare. The aim of the present study was to compare the efficacy of three widely applied stimulation methods inducing excitability enhancement in the motor cortex: 1 mA anodal transcranial direct current stimulation (atDCS, intermittent theta burst stimulation (iTBS, and 1 mA transcranial random noise stimulation (tRNS within one subject group. The effect of each stimulation condition was quantified by evaluating motor-evoked-potential amplitudes (MEPs in a fixed time sequence after stimulation. The analyses confirmed a significant enhancement of the M1 excitability caused by all three types of active stimulations compared to sham stimulation. There was no significant difference between the types of active stimulations, although the time course of the excitatory effects slightly differed. Among the stimulation methods, tRNS resulted in the strongest and atDCS significantly longest MEP increase compared to sham. Different time courses of the applied stimulation methods suggest different underlying mechanisms of action. Better understanding may be useful for better targeting of different transcranial stimulation techniques.

  2. Dynamic inhibition of excitatory synaptic transmission by astrocyte-derived ATP in hippocampal cultures

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    Koizumi, Schuichi; Fujishita, Kayoko; Tsuda, Makoto; Shigemoto-Mogami, Yukari; Inoue, Kazuhide

    2003-09-01

    Originally ascribed passive roles in the CNS, astrocytes are now known to have an active role in the regulation of synaptic transmission. Neuronal activity can evoke Ca2+ transients in astrocytes, and Ca2+ transients in astrocytes can evoke changes in neuronal activity. The excitatory neurotransmitter glutamate has been shown to mediate such bidirectional communication between astrocytes and neurons. We demonstrate here that ATP, a primary mediator of intercellular Ca2+ signaling among astrocytes, also mediates intercellular signaling between astrocytes and neurons in hippocampal cultures. Mechanical stimulation of astrocytes evoked Ca2+ waves mediated by the release of ATP and the activation of P2 receptors. Mechanically evoked Ca2+ waves led to decreased excitatory glutamatergic synaptic transmission in an ATP-dependent manner. Exogenous application of ATP does not affect postsynaptic glutamatergic responses but decreased presynaptic exocytotic events. Finally, we show that astrocytes exhibit spontaneous Ca2+ waves mediated by extracellular ATP and that inhibition of these Ca2+ responses enhanced excitatory glutamatergic transmission. We therefore conclude that ATP released from astrocytes exerts tonic and activity-dependent down-regulation of synaptic transmission via presynaptic mechanisms.

  3. Plasticity of cortical excitatory-inhibitory balance.

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    Froemke, Robert C

    2015-07-08

    Synapses are highly plastic and are modified by changes in patterns of neural activity or sensory experience. Plasticity of cortical excitatory synapses is thought to be important for learning and memory, leading to alterations in sensory representations and cognitive maps. However, these changes must be coordinated across other synapses within local circuits to preserve neural coding schemes and the organization of excitatory and inhibitory inputs, i.e., excitatory-inhibitory balance. Recent studies indicate that inhibitory synapses are also plastic and are controlled directly by a large number of neuromodulators, particularly during episodes of learning. Many modulators transiently alter excitatory-inhibitory balance by decreasing inhibition, and thus disinhibition has emerged as a major mechanism by which neuromodulation might enable long-term synaptic modifications naturally. This review examines the relationships between neuromodulation and synaptic plasticity, focusing on the induction of long-term changes that collectively enhance cortical excitatory-inhibitory balance for improving perception and behavior.

  4. Role of cyclooxygenase isoforms in the altered excitatory motor pathways of human colon with diverticular disease.

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    Fornai, M; Colucci, R; Antonioli, L; Ippolito, C; Segnani, C; Buccianti, P; Marioni, A; Chiarugi, M; Villanacci, V; Bassotti, G; Blandizzi, C; Bernardini, N

    2014-08-01

    The COX isoforms (COX-1, COX-2) regulate human gut motility, although their role under pathological conditions remains unclear. This study examines the effects of COX inhibitors on excitatory motility in colonic tissue from patients with diverticular disease (DD). Longitudinal muscle preparations, from patients with DD or uncomplicated cancer (controls), were set up in organ baths and connected to isotonic transducers. Indomethacin (COX-1/COX-2 inhibitor), SC-560 (COX-1 inhibitor) or DFU (COX-2 inhibitor) were assayed on electrically evoked, neurogenic, cholinergic and tachykininergic contractions, or carbachol- and substance P (SP)-induced myogenic contractions. Distribution and expression of COX isoforms in the neuromuscular compartment were assessed by RT-PCR, Western blot and immunohistochemical analysis. In control preparations, neurogenic cholinergic contractions were enhanced by COX inhibitors, whereas tachykininergic responses were blunted. Carbachol-evoked contractions were increased by indomethacin or SC-560, but not DFU, whereas all inhibitors reduced SP-induced motor responses. In preparations from DD patients, COX inhibitors did not affect electrically evoked cholinergic contractions. Both indomethacin and DFU, but not SC-560, decreased tachykininergic responses. COX inhibitors did not modify carbachol-evoked motor responses, whereas they counteracted SP-induced contractions. COX-1 expression was decreased in myenteric neurons, whereas COX-2 was enhanced in glial cells and smooth muscle. In control colon, COX-1 and COX-2 down-regulate cholinergic motility, whereas both isoforms enhance tachykininergic motor activity. In the presence of DD, there is a loss of modulation by both COX isoforms on the cholinergic system, whereas COX-2 displays an enhanced facilitatory control on tachykininergic contractile activity. © 2014 The British Pharmacological Society.

  5. Excitatory effect of the A2A adenosine receptor agonist CGS-21680 on spontaneous and K+-evoked acetylcholine release at the mouse neuromuscular junction.

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    Palma, A G; Muchnik, S; Losavio, A S

    2011-01-13

    The mechanism of action of the A2A adenosine receptor agonist 2-p-(2-carboxyethyl) phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride (CGS-21680) in the facilitation of spontaneous (isotonic and hypertonic condition) and K+-evoked acetylcholine (ACh) release was investigated in the mouse diaphragm muscles. At isotonic condition, the CGS-21680-induced excitatory effect on miniature end-plate potential (MEPP) frequency was not modified in the presence of CdCl2 and in a medium free of Ca2+ (0Ca2+-EGTA), but it was abolished after buffering the rise of intracellular Ca2+ with 1,2-bis-(2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid tetra(acetoxy-methyl) (BAPTA-AM) and when the Ca2+-ATPase inhibitor thapsigargin was used to deplete intracellular Ca2+ stores. CGS-21680 did not have a direct effect on the Ca2+-independent neurotransmitter-releasing machinery, since the modulatory effect on the hypertonic response was also occluded by BAPTA-AM and thapsigargin. CGS-21680 facilitation on K+-evoked ACh release was not altered by the P/Q-type voltage-dependent calcium channel (VDCC) blocker ω-Agatoxin IVA, but it was completely prevented by both, the L-type VDCC blocker nitrendipine (which is known to immobilize their gating charges), or thapsigargin, suggesting that the effects of CGS-21680 on L-type VDCC and thapsigargin-sensitive internal stores are associated. We found that the VDCC pore blocker Cd2+ (2 mM Ca2+ or 0Ca2+-EGTA) failed to affect the CGS-21680 effect in high K+ whereas nitrendipine in 0Ca2+-EGTA+Cd2+ occluded its action. The blockade of Ca2+ release from endoplasmic reticulum with ryanodine antagonized the facilitating effect of CGS-21680 in control and high K+ concentration. It is concluded that, at the mouse neuromuscular junction, activation of A2A receptors facilitates spontaneous and K+-evoked ACh release by an external Ca2+-independent mechanism but that involves mobilization of Ca2+ from internal stores: during spontaneous ACh release

  6. Reversed synaptic effects of hypocretin and NPY mediated by excitatory GABA-dependent synaptic activity in developing MCH neurons.

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    Li, Ying; Xu, Youfen; van den Pol, Anthony N

    2013-03-01

    In mature neurons, GABA is the primary inhibitory neurotransmitter. In contrast, in developing neurons, GABA exerts excitatory actions, and in some neurons GABA-mediated excitatory synaptic activity is more prevalent than glutamate-mediated excitation. Hypothalamic neuropeptides that modulate cognitive arousal and energy homeostasis, hypocretin/orexin and neuropeptide Y (NPY), evoked reversed effects on synaptic actions that were dependent on presynaptic GABA release onto melanin-concentrating hormone (MCH) neurons. MCH neurons were identified by selective green fluorescent protein (GFP) expression in transgenic mice. In adults, hypocretin increased GABA release leading to reduced excitation. In contrast, in the developing brain as studied here with analysis of miniature excitatory postsynaptic currents, paired-pulse ratios, and evoked potentials, hypocretin acted presynaptically to enhance the excitatory actions of GABA. The ability of hypocretin to enhance GABA release increases inhibition in adult neurons but paradoxically enhances excitation in developing MCH neurons. In contrast, NPY attenuation of GABA release reduced inhibition in mature neurons but enhanced inhibition during development by attenuating GABA excitation. Both hypocretin and NPY also evoked direct actions on developing MCH neurons. Hypocretin excited MCH cells by activating a sodium-calcium exchanger and by reducing potassium currents; NPY reduced activity by increasing an inwardly rectifying potassium current. These data for the first time show that both hypocretin and NPY receptors are functional presynaptically during early postnatal hypothalamic development and that both neuropeptides modulate GABA actions during development with a valence of enhanced excitation or inhibition opposite to that of the adult state, potentially allowing neuropeptide modulation of use-dependent synapse stabilization.

  7. Streptozotocin Inhibits Electrophysiological Determinants of Excitatory and Inhibitory Synaptic Transmission in CA1 Pyramidal Neurons of Rat Hippocampal Slices: Reduction of These Effects by Edaravone

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    Ting Ju

    2016-12-01

    Full Text Available Background: Streptozotocin (STZ has served as an agent to generate an Alzheimer's disease (AD model in rats, while edaravone (EDA, a novel free radical scavenger, has recently emerged as an effective treatment for use in vivo and vitro AD models. However, to date, these beneficial effects of EDA have only been clearly demonstrated within STZ-induced animal models of AD and in cell models of AD. A better understanding of the mechanisms of EDA may provide the opportunity for their clinical application in the treatment of AD. Therefore, the purpose of this study was to investigate the underlying mechanisms of STZ and EDA as assessed upon electrophysiological alterations in CA1 pyramidal neurons of rat hippocampal slices. Methods: Through measures of evoked excitatory postsynaptic currents (eEPSCs, AMPAR-mediated eEPSCs (eEPSCsAMPA, evoked inhibitory postsynaptic currents (eIPSCs, evoked excitatory postsynaptic current paired pulse ratio (eEPSC PPR and evoked inhibitory postsynaptic current paired pulse ratio (eIPSC PPR, it was possible to investigate mechanisms as related to the neurotoxicity of STZ and reductions in these effects by EDA. Results: Our results showed that STZ (1000 µM significantly inhibited peak amplitudes of eEPSCs, eEPSCsAMPA and eIPSCs, while EDA (1000 µM attenuated these STZ-induced changes at holding potentials ranging from -60mV to +40 mV for EPSCs and -60mV to +20 mV for IPSCs. Our work also indicated that mean eEPSC PPR were substantially altered by STZ, effects which were partially restored by EDA. In contrast, no significant effects upon eIPSC PPR were obtained in response to STZ and EDA. Conclusion: Our data suggest that STZ inhibits glutamatergic transmission involving pre-synaptic mechanisms and AMPAR, and that STZ inhibits GABAergic transmission by post-synaptic mechanisms within CA1 pyramidal neurons. These effects are attenuated by EDA.

  8. LRRTM3 Regulates Excitatory Synapse Development through Alternative Splicing and Neurexin Binding

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    Ji Won Um

    2016-02-01

    Full Text Available The four members of the LRRTM family (LRRTM1-4 are postsynaptic adhesion molecules essential for excitatory synapse development. They have also been implicated in neuropsychiatric diseases. Here, we focus on LRRTM3, showing that two distinct LRRTM3 variants generated by alternative splicing regulate LRRTM3 interaction with PSD-95, but not its excitatory synapse-promoting activity. Overexpression of either LRRTM3 variant increased excitatory synapse density in dentate gyrus (DG granule neurons, whereas LRRTM3 knockdown decreased it. LRRTM3 also controlled activity-regulated AMPA receptor surface expression in an alternative splicing-dependent manner. Furthermore, Lrrtm3-knockout mice displayed specific alterations in excitatory synapse density, excitatory synaptic transmission and excitability in DG granule neurons but not in CA1 pyramidal neurons. Lastly, LRRTM3 required only specific splice variants of presynaptic neurexins for their synaptogenic activity. Collectively, our data highlight alternative splicing and differential presynaptic ligand utilization in the regulation of LRRTMs, revealing key regulatory mechanisms for excitatory synapse development.

  9. Visual cortex plasticity evokes excitatory alterations in the hippocampus

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    Marian Tsanov

    2009-11-01

    Full Text Available The integration of episodic sequences in the hippocampus is believed to occur during theta rhythm episodes, when cortico-hippocampal dialog results in reconfiguration of neuronal assemblies. As the visual cortex (VC is a major source of sensory information to the hippocampus, information processing in the cortex may affect hippocampal network oscillations, facilitating the induction of synaptic modifications. We investigated to what degree the field activity in the primary VC, elicited by sensory or electrical stimulation, correlates with hippocampal oscillatory and synaptic responsiveness, in freely behaving adult rats. We found that the spectral power of theta rhythm (4-10Hz in the dentate gyrus (DG, increases in parallel with high-frequency oscillations in layer 2/3 of the VC and that this correlation depends on the degree of exploratory activity. When we mimic robust thalamocortical activity by theta-burst application to dorsal lateral geniculate nucleus, a hippocampal theta increase occurs, followed by a persistent potentiation of the DG granule field population spike. Furthermore, the potentiation of DG neuronal excitability tightly correlates with the concurrently occurring VC plasticity. The concurrent enhancement of VC and DG activity is also combined with a highly negative synchronization between hippocampal and cortical low frequency oscillations. Exploration of familiar environment decreases the degree of this synchrony. Our data propose that novel visual information can induce high-power fluctuations in intrinsic excitability for both VC and hippocampus, potent enough to induce experience-dependent modulation of cortico-hippocampal connections. This interaction may comprise one of the endogenous triggers for long-term synaptic plasticity in the hippocampus.

  10. Low-intensity focused ultrasound alters the latency and spatial patterns of sensory-evoked cortical responses in vivo

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    Fisher, Jonathan A. N.; Gumenchuk, Iryna

    2018-06-01

    Objective. The use of transcranial, low intensity focused ultrasound (FUS) is an emerging neuromodulation technology that shows promise for both therapeutic and research applications. Among many, one of the most exciting applications is the use of FUS to rehabilitate or augment human sensory capabilities. While there is compelling empirical evidence demonstrating this capability, basic questions regarding the spatiotemporal extent of the modulatory effects remain. Our objective was to assess the basic, yet often overlooked hypothesis that FUS in fact alters sensory-evoked neural activity within the region of the cerebral cortex at the beam’s focus. Approach. To address this knowledge gap, we developed an approach to optically interrogate patterns of neural activity in the cortex directly at the acoustic focus, in vivo. Implementing simultaneous wide-field optical imaging and FUS stimulation in mice, our experiments probed somatosensory-evoked electrical activity through the use of voltage sensitive dyes (VSDs) and, in transgenic mice expressing GCaMP6f, monitored associated Ca2+ responses. Main results. Our results demonstrate that low-intensity FUS alters both the kinetics and spatial patterns of neural activity in primary somatosensory cortex at the acoustic focus. When preceded by 1 s of pulsed ultrasound at intensities below 1 W cm‑2 (I sppa), the onset of sensory-evoked cortical responses occurred 3.0  ±  0.7 ms earlier and altered the surface spatial morphology of Ca2+ responses. Significance. These findings support the heretofore unconfirmed assumption that FUS-induced sensory modulation reflects, at least in part, altered reactivity in primary sensory cortex at the site of sonication. The findings are significant given the interest in using FUS to target and alter spatial aspects of sensory receptive fields on the cerebral cortex.

  11. Low-intensity focused ultrasound alters the latency and spatial patterns of sensory-evoked cortical responses in vivo.

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    Fisher, Jonathan A N; Gumenchuk, Iryna

    2018-02-13

    The use of transcranial, low intensity focused ultrasound (FUS) is an emerging neuromodulation technology that shows promise for both therapeutic and research applications. Among many, one of the most exciting applications is the use of FUS to rehabilitate or augment human sensory capabilities. While there is compelling empirical evidence demonstrating this capability, basic questions regarding the spatiotemporal extent of the modulatory effects remain. Our objective was to assess the basic, yet often overlooked hypothesis that FUS in fact alters sensory-evoked neural activity within the region of the cerebral cortex at the beam's focus. To address this knowledge gap, we developed an approach to optically interrogate patterns of neural activity in the cortex directly at the acoustic focus, in vivo. Implementing simultaneous wide-field optical imaging and FUS stimulation in mice, our experiments probed somatosensory-evoked electrical activity through the use of voltage sensitive dyes (VSDs) and, in transgenic mice expressing GCaMP6f, monitored associated Ca 2+ responses. Our results demonstrate that low-intensity FUS alters both the kinetics and spatial patterns of neural activity in primary somatosensory cortex at the acoustic focus. When preceded by 1 s of pulsed ultrasound at intensities below 1 W cm -2 (I sppa ), the onset of sensory-evoked cortical responses occurred 3.0  ±  0.7 ms earlier and altered the surface spatial morphology of Ca 2+ responses. These findings support the heretofore unconfirmed assumption that FUS-induced sensory modulation reflects, at least in part, altered reactivity in primary sensory cortex at the site of sonication. The findings are significant given the interest in using FUS to target and alter spatial aspects of sensory receptive fields on the cerebral cortex.

  12. Dynamics of excitatory and inhibitory networks are differentially altered by selective attention

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    Snyder, Adam C.; Morais, Michael J.

    2016-01-01

    Inhibition and excitation form two fundamental modes of neuronal interaction, yet we understand relatively little about their distinct roles in service of perceptual and cognitive processes. We developed a multidimensional waveform analysis to identify fast-spiking (putative inhibitory) and regular-spiking (putative excitatory) neurons in vivo and used this method to analyze how attention affects these two cell classes in visual area V4 of the extrastriate cortex of rhesus macaques. We found that putative inhibitory neurons had both greater increases in firing rate and decreases in correlated variability with attention compared with putative excitatory neurons. Moreover, the time course of attention effects for putative inhibitory neurons more closely tracked the temporal statistics of target probability in our task. Finally, the session-to-session variability in a behavioral measure of attention covaried with the magnitude of this effect. Together, these results suggest that selective targeting of inhibitory neurons and networks is a critical mechanism for attentional modulation. PMID:27466133

  13. Dynamics of excitatory and inhibitory networks are differentially altered by selective attention.

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    Snyder, Adam C; Morais, Michael J; Smith, Matthew A

    2016-10-01

    Inhibition and excitation form two fundamental modes of neuronal interaction, yet we understand relatively little about their distinct roles in service of perceptual and cognitive processes. We developed a multidimensional waveform analysis to identify fast-spiking (putative inhibitory) and regular-spiking (putative excitatory) neurons in vivo and used this method to analyze how attention affects these two cell classes in visual area V4 of the extrastriate cortex of rhesus macaques. We found that putative inhibitory neurons had both greater increases in firing rate and decreases in correlated variability with attention compared with putative excitatory neurons. Moreover, the time course of attention effects for putative inhibitory neurons more closely tracked the temporal statistics of target probability in our task. Finally, the session-to-session variability in a behavioral measure of attention covaried with the magnitude of this effect. Together, these results suggest that selective targeting of inhibitory neurons and networks is a critical mechanism for attentional modulation. Copyright © 2016 the American Physiological Society.

  14. Altered excitatory-inhibitory balance in the NMDA-hypofunction model of schizophrenia

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    Colin Kehrer

    2008-04-01

    Full Text Available Schizophrenia is a common psychiatric disorder of high incidence, affecting approximately 1% of the world population. The essential neurotransmitter pathology of schizophrenia remains poorly defined, despite huge advances over the past half-century in identifying neurochemical and pathological abnormalities in the disease. The dopamine/serotonin hypothesis has originally provided much of the momentum for neurochemical research in schizophrenia. In recent years, the attention has, however, shifted to the glutamate system, the major excitatory neurotransmitter in the CNS and towards a concept of functional imbalance between excitatory and inhibitory transmission at the network level in various brain regions in schizophrenia. The evidence indicating a central role for the NMDAreceptor subtype in the etiology of schizophrenia has led to the NMDA-hypofunction model of this disease and the use of phencyclidines as a means to induce the NMDA-hypofunction state in animal models. The purpose of this review is to discuss recent findings highlighting the importance of the NMDA-hypofunction model of schizophrenia, both from a clinical perspective, as well as in opening a line of research, which enables electrophysiological studies at the cellular and network level in vitro. In particular, changes in excitation-inhibition (E/I balance in the NMDA-hypofunction model of the disease and the resulting changes in network behaviours, particularly in gamma frequency oscillatory activity, will be discussed.

  15. Brainstem Auditory Evoked Potential in HIV-Positive Adults.

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    Matas, Carla Gentile; Samelli, Alessandra Giannella; Angrisani, Rosanna Giaffredo; Magliaro, Fernanda Cristina Leite; Segurado, Aluísio C

    2015-10-20

    To characterize the findings of brainstem auditory evoked potential in HIV-positive individuals exposed and not exposed to antiretroviral treatment. This research was a cross-sectional, observational, and descriptive study. Forty-five HIV-positive individuals (18 not exposed and 27 exposed to the antiretroviral treatment - research groups I and II, respectively - and 30 control group individuals) were assessed through brainstem auditory evoked potential. There were no significant between-group differences regarding wave latencies. A higher percentage of altered brainstem auditory evoked potential was observed in the HIV-positive groups when compared to the control group. The most common alteration was in the low brainstem. HIV-positive individuals have a higher percentage of altered brainstem auditory evoked potential that suggests central auditory pathway impairment when compared to HIV-negative individuals. There was no significant difference between individuals exposed and not exposed to antiretroviral treatment.

  16. Effects of Neuromodulation on Excitatory-Inhibitory Neural Network Dynamics Depend on Network Connectivity Structure

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    Rich, Scott; Zochowski, Michal; Booth, Victoria

    2018-01-01

    Acetylcholine (ACh), one of the brain's most potent neuromodulators, can affect intrinsic neuron properties through blockade of an M-type potassium current. The effect of ACh on excitatory and inhibitory cells with this potassium channel modulates their membrane excitability, which in turn affects their tendency to synchronize in networks. Here, we study the resulting changes in dynamics in networks with inter-connected excitatory and inhibitory populations (E-I networks), which are ubiquitous in the brain. Utilizing biophysical models of E-I networks, we analyze how the network connectivity structure in terms of synaptic connectivity alters the influence of ACh on the generation of synchronous excitatory bursting. We investigate networks containing all combinations of excitatory and inhibitory cells with high (Type I properties) or low (Type II properties) modulatory tone. To vary network connectivity structure, we focus on the effects of the strengths of inter-connections between excitatory and inhibitory cells (E-I synapses and I-E synapses), and the strengths of intra-connections among excitatory cells (E-E synapses) and among inhibitory cells (I-I synapses). We show that the presence of ACh may or may not affect the generation of network synchrony depending on the network connectivity. Specifically, strong network inter-connectivity induces synchronous excitatory bursting regardless of the cellular propensity for synchronization, which aligns with predictions of the PING model. However, when a network's intra-connectivity dominates its inter-connectivity, the propensity for synchrony of either inhibitory or excitatory cells can determine the generation of network-wide bursting.

  17. Synaptic responses evoked by tactile stimuli in Purkinje cells in mouse cerebellar cortex Crus II in vivo.

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    Chun-Ping Chu

    Full Text Available Sensory stimuli evoke responses in cerebellar Purkinje cells (PCs via the mossy fiber-granule cell pathway. However, the properties of synaptic responses evoked by tactile stimulation in cerebellar PCs are unknown. The present study investigated the synaptic responses of PCs in response to an air-puff stimulation on the ipsilateral whisker pad in urethane-anesthetized mice.Thirty-three PCs were recorded from 48 urethane-anesthetized adult (6-8-week-old HA/ICR mice by somatic or dendritic patch-clamp recording and pharmacological methods. Tactile stimulation to the ipsilateral whisker pad was delivered by an air-puff through a 12-gauge stainless steel tube connected with a pressurized injection system. Under current-clamp conditions (I = 0, the air-puff stimulation evoked strong inhibitory postsynaptic potentials (IPSPs in the somata of PCs. Application of SR95531, a specific GABA(A receptor antagonist, blocked IPSPs and revealed stimulation-evoked simple spike firing. Under voltage-clamp conditions, tactile stimulation evoked a sequence of transient inward currents followed by strong outward currents in the somata and dendrites in PCs. Application of SR95531 blocked outward currents and revealed excitatory postsynaptic currents (EPSCs in somata and a temporal summation of parallel fiber EPSCs in PC dendrites. We also demonstrated that PCs respond to both the onset and offset of the air-puff stimulation.These findings indicated that tactile stimulation induced asynchronous parallel fiber excitatory inputs onto the dendrites of PCs, and failed to evoke strong EPSCs and spike firing in PCs, but induced the rapid activation of strong GABA(A receptor-mediated inhibitory postsynaptic currents in the somata and dendrites of PCs in the cerebellar cortex Crus II in urethane-anesthetized mice.

  18. Selective synaptic targeting of the excitatory and inhibitory presynaptic organizers FGF22 and FGF7.

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    Terauchi, Akiko; Timmons, Kendall M; Kikuma, Koto; Pechmann, Yvonne; Kneussel, Matthias; Umemori, Hisashi

    2015-01-15

    Specific formation of excitatory and inhibitory synapses is crucial for proper functioning of the brain. Fibroblast growth factor 22 (FGF22) and FGF7 are postsynaptic-cell-derived presynaptic organizers necessary for excitatory and inhibitory presynaptic differentiation, respectively, in the hippocampus. For the establishment of specific synaptic networks, these FGFs must localize to appropriate synaptic locations - FGF22 to excitatory and FGF7 to inhibitory postsynaptic sites. Here, we show that distinct motor and adaptor proteins contribute to intracellular microtubule transport of FGF22 and FGF7. Excitatory synaptic targeting of FGF22 requires the motor proteins KIF3A and KIF17 and the adaptor protein SAP102 (also known as DLG3). By contrast, inhibitory synaptic targeting of FGF7 requires the motor KIF5 and the adaptor gephyrin. Time-lapse imaging shows that FGF22 moves with SAP102, whereas FGF7 moves with gephyrin. These results reveal the basis of selective targeting of the excitatory and inhibitory presynaptic organizers that supports their different synaptogenic functions. Finally, we found that knockdown of SAP102 or PSD95 (also known as DLG4), which impairs the differentiation of excitatory synapses, alters FGF7 localization, suggesting that signals from excitatory synapses might regulate inhibitory synapse formation by controlling the distribution of the inhibitory presynaptic organizer. © 2015. Published by The Company of Biologists Ltd.

  19. Alterations of excitatory transmission in the lateral amygdala during expression and extinction of fear memory.

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    Lin, Hui-Ching; Mao, Sheng-Chun; Su, Chun-Lin; Gean, Po-Wu

    2010-04-01

    Understanding the neurophysiology of fear extinction has important implications for the treatment of post-traumatic stress disorders. Here we report that fear conditioning resulted in an increase in AMPA/NMDA ratio as well as depression of paired-pulse facilitation (PPF) in neurons of the lateral nucleus of amygdala. These conditioning-induced changes in synaptic transmission were not affected by extinction training. D-cycloserine (DCS), a partial agonist at the glycine-binding site of the NMDA receptor, facilitated extinction and reversed the increase in AMPA/NMDA ratio without altering the depression of PPF when administered before extinction training. Extinction training, however, significantly increased the frequency and amplitude of miniature inhibitory post-synaptic currents and these effects were unaffected by the DCS treatment. Disruption of AMPA receptor endocytosis with a synthetic peptide containing a short C-terminal sequence of GluR2 (869YKEGYNVYG877, GluR23Y) specifically blocked DCS-induced reversal of AMPA/NMDA ratio and the facilitation of extinction. These results suggest that extinction training mainly increases inhibitory transmission leaving conditioning-induced excitatory association unaltered. DCS does not affect inhibitory transmission but reverses the conditioning-induced post-synaptic memory trace when administered before extinction training.

  20. Maturation- and sex-sensitive depression of hippocampal excitatory transmission in a rat schizophrenia model.

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    Patrich, Eti; Piontkewitz, Yael; Peretz, Asher; Weiner, Ina; Attali, Bernard

    2016-01-01

    Schizophrenia is associated with behavioral and brain structural abnormalities, of which the hippocampus appears to be one of the most consistent region affected. Previous studies performed on the poly I:C model of schizophrenia suggest that alterations in hippocampal synaptic transmission and plasticity take place in the offspring. However, these investigations yielded conflicting results and the neurophysiological alterations responsible for these deficits are still unclear. Here we performed for the first time a longitudinal study examining the impact of prenatal poly I:C treatment and of gender on hippocampal excitatory neurotransmission. In addition, we examined the potential preventive/curative effects of risperidone (RIS) treatment during the peri-adolescence period. Excitatory synaptic transmission was determined by stimulating Schaffer collaterals and monitoring fiber volley amplitude and slope of field-EPSP (fEPSP) in CA1 pyramidal neurons in male and female offspring hippocampal slices from postnatal days (PNDs) 18-20, 34, 70 and 90. Depression of hippocampal excitatory transmission appeared at juvenile age in male offspring of the poly I:C group, while it expressed with a delay in female, manifesting at adulthood. In addition, a reduced hippocampal size was found in both adult male and female offspring of poly I:C treated dams. Treatment with RIS at the peri-adolescence period fully restored in males but partly repaired in females these deficiencies. A maturation- and sex-dependent decrease in hippocampal excitatory transmission occurs in the offspring of poly I:C treated pregnant mothers. Pharmacological intervention with RIS during peri-adolescence can cure in a gender-sensitive fashion early occurring hippocampal synaptic deficits. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Anaplastic Lymphoma Kinase Is a Regulator of Alcohol Consumption and Excitatory Synaptic Plasticity in the Nucleus Accumbens Shell

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    Regina A. Mangieri

    2017-08-01

    Full Text Available Anaplastic lymphoma kinase (ALK is a receptor tyrosine kinase recently implicated in biochemical, physiological, and behavioral responses to ethanol. Thus, manipulation of ALK signaling may represent a novel approach to treating alcohol use disorder (AUD. Ethanol induces adaptations in glutamatergic synapses onto nucleus accumbens shell (NAcSh medium spiny neurons (MSNs, and putative targets for treating AUD may be validated for further development by assessing how their manipulation modulates accumbal glutamatergic synaptic transmission and plasticity. Here, we report that Alk knockout (AlkKO mice consumed greater doses of ethanol, relative to wild-type (AlkWT mice, in an operant self-administration model. Using ex vivo electrophysiology to examine excitatory synaptic transmission and plasticity at NAcSh MSNs that express dopamine D1 receptors (D1MSNs, we found that the amplitude of spontaneous excitatory post-synaptic currents (EPSCs in NAcSh D1MSNs was elevated in AlkKO mice and in the presence of an ALK inhibitor, TAE684. Furthermore, when ALK was absent or inhibited, glutamatergic synaptic plasticity – long-term depression of evoked EPSCs – in D1MSNs was attenuated. Thus, loss of ALK activity in mice is associated with elevated ethanol consumption and enhanced excitatory transmission in NAcSh D1MSNs. These findings add to the mounting evidence of a relationship between excitatory synaptic transmission onto NAcSh D1MSNs and ethanol consumption, point toward ALK as one important molecular mediator of this interaction, and further validate ALK as a target for therapeutic intervention in the treatment of AUD.

  2. Nitric oxide-related species inhibit evoked neurotransmission but enhance spontaneous miniature synaptic currents in central neuronal cultures

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    Pan, Zhuo-Hua; Segal, Michael M.; Lipton, Stuart A.

    1996-01-01

    Nitric oxide (NO·) does not react significantly with thiol groups under physiological conditions, whereas a variety of endogenous NO donor molecules facilitate rapid transfer to thiol of nitrosonium ion (NO+, with one less electron than NO·). Here, nitrosonium donors are shown to decrease the efficacy of evoked neurotransmission while increasing the frequency of spontaneous miniature excitatory postsynaptic currents (mEPSCs). In contrast, pure NO· donors have littl...

  3. Mechanism underlying unaltered cortical inhibitory synaptic transmission in contrast with enhanced excitatory transmission in CaV2.1 knockin migraine mice

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    Vecchia, Dania; Tottene, Angelita; van den Maagdenberg, Arn M.J.M.; Pietrobon, Daniela

    2014-01-01

    Familial hemiplegic migraine type 1 (FHM1), a monogenic subtype of migraine with aura, is caused by gain-of-function mutations in CaV2.1 (P/Q-type) calcium channels. In FHM1 knockin mice, excitatory neurotransmission at cortical pyramidal cell synapses is enhanced, but inhibitory neurotransmission at connected pairs of fast-spiking (FS) interneurons and pyramidal cells is unaltered, despite being initiated by CaV2.1 channels. The mechanism underlying the unaltered GABA release at cortical FS interneuron synapses remains unknown. Here, we show that the FHM1 R192Q mutation does not affect inhibitory transmission at autapses of cortical FS and other types of multipolar interneurons in microculture from R192Q knockin mice, and investigate the underlying mechanism. Lowering the extracellular [Ca2+] did not reveal gain-of-function of evoked transmission neither in control nor after prolongation of the action potential (AP) with tetraethylammonium, indicating unaltered AP-evoked presynaptic calcium influx at inhibitory autapses in FHM1 KI mice. Neither saturation of the presynaptic calcium sensor nor short duration of the AP can explain the unaltered inhibitory transmission in the mutant mice. Recordings of the P/Q-type calcium current in multipolar interneurons in microculture revealed that the current density and the gating properties of the CaV2.1 channels expressed in these interneurons are barely affected by the FHM1 mutation, in contrast with the enhanced current density and left-shifted activation gating of mutant CaV2.1 channels in cortical pyramidal cells. Our findings suggest that expression of specific CaV2.1 channels differentially sensitive to modulation by FHM1 mutations in inhibitory and excitatory cortical neurons underlies the gain-of-function of excitatory but unaltered inhibitory synaptic transmission and the likely consequent dysregulation of the cortical excitatory–inhibitory balance in FHM1. PMID:24907493

  4. Skin denervation does not alter cortical potentials to surface concentric electrode stimulation: A comparison with laser evoked potentials and contact heat evoked potentials.

    Science.gov (United States)

    La Cesa, S; Di Stefano, G; Leone, C; Pepe, A; Galosi, E; Alu, F; Fasolino, A; Cruccu, G; Valeriani, M; Truini, A

    2018-01-01

    In the neurophysiological assessment of patients with neuropathic pain, laser evoked potentials (LEPs), contact heat evoked potentials (CHEPs) and the evoked potentials by the intraepidermal electrical stimulation via concentric needle electrode are widely agreed as nociceptive specific responses; conversely, the nociceptive specificity of evoked potentials by surface concentric electrode (SE-PREPs) is still debated. In this neurophysiological study we aimed at verifying the nociceptive specificity of SE-PREPs. We recorded LEPs, CHEPs and SE-PREPs in eleven healthy participants, before and after epidermal denervation produced by prolonged capsaicin application. We also used skin biopsy to verify the capsaicin-induced nociceptive nerve fibre loss in the epidermis. We found that whereas LEPs and CHEPs were suppressed after capsaicin-induced epidermal denervation, the surface concentric electrode stimulation of the same denervated skin area yielded unchanged SE-PREPs. The suppression of LEPs and CHEPs after nociceptive nerve fibre loss in the epidermis indicates that these techniques are selectively mediated by nociceptive system. Conversely, the lack of SE-PREP changes suggests that SE-PREPs do not provide selective information on nociceptive system function. Capsaicin-induced epidermal denervation abolishes laser evoked potentials (LEPs) and contact heat evoked potentials (CHEPs), but leaves unaffected pain-related evoked potentials by surface concentric electrode (SE-PREPs). These findings suggest that unlike LEPs and CHEPs, SE-PREPs are not selectively mediated by nociceptive system. © 2017 European Pain Federation - EFIC®.

  5. Excitatory amino acid receptors and disease.

    Science.gov (United States)

    Meldrum, B S

    1992-08-01

    Recent advances in the molecular biology of excitatory amino acid receptors are reviewed. Evidence that drugs blocking the excitatory action of glutamate at the N-methyl-D-aspartate (NMDA) and non-NMDA receptors may be of clinical use in epilepsy, Parkinson's disease, cerebral ischaemia and trauma, acquired immune deficiency syndrome (AIDS) encephalopathy and neuropathic pain is summarized.

  6. TGF-β Signaling in Dopaminergic Neurons Regulates Dendritic Growth, Excitatory-Inhibitory Synaptic Balance, and Reversal Learning

    Directory of Open Access Journals (Sweden)

    Sarah X. Luo

    2016-12-01

    Full Text Available Neural circuits involving midbrain dopaminergic (DA neurons regulate reward and goal-directed behaviors. Although local GABAergic input is known to modulate DA circuits, the mechanism that controls excitatory/inhibitory synaptic balance in DA neurons remains unclear. Here, we show that DA neurons use autocrine transforming growth factor β (TGF-β signaling to promote the growth of axons and dendrites. Surprisingly, removing TGF-β type II receptor in DA neurons also disrupts the balance in TGF-β1 expression in DA neurons and neighboring GABAergic neurons, which increases inhibitory input, reduces excitatory synaptic input, and alters phasic firing patterns in DA neurons. Mice lacking TGF-β signaling in DA neurons are hyperactive and exhibit inflexibility in relinquishing learned behaviors and re-establishing new stimulus-reward associations. These results support a role for TGF-β in regulating the delicate balance of excitatory/inhibitory synaptic input in local microcircuits involving DA and GABAergic neurons and its potential contributions to neuropsychiatric disorders.

  7. Network models predict that reduced excitatory fluctuations can give rise to hippocampal network hyper-excitability in MeCP2-null mice.

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    Ernest C Y Ho

    Full Text Available Rett syndrome is a severe pediatric neurological disorder caused by loss of function mutations within the gene encoding methyl CpG-binding protein 2 (MeCP2. Although MeCP2 is expressed near ubiquitously, the primary pathophysiology of Rett syndrome stems from impairments of nervous system function. One alteration within different regions of the MeCP2-deficient brain is the presence of hyper-excitable network responses. In the hippocampus, such responses exist despite there being an overall decrease in spontaneous excitatory drive within the network. In this study, we generated and used mathematical, neuronal network models to resolve this apparent paradox. We did this by taking advantage of previous mathematical modelling insights that indicated that decreased excitatory fluctuations, but not mean excitatory drive, more critically explain observed changes in hippocampal network oscillations from MeCP2-null mouse slices. Importantly, reduced excitatory fluctuations could also bring about hyper-excitable responses in our network models. Therefore, these results indicate that diminished excitatory fluctuations may be responsible for the hyper-excitable state of MeCP2-deficient hippocampal circuitry.

  8. Excitatory amino acid receptors mediate asymmetry and lateralization in the descending cardiovascular pathways from the dorsomedial hypothalamus.

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    Carlos Henrique Xavier

    Full Text Available The dorsomedial hypothalamus (DMH and lateral/dorsolateral periaqueductal gray (PAG are anatomically and functionally connected. Both the DMH and PAG depend on glutamatergic inputs for activation. We recently reported that removal of GABA-ergic tone in the unilateral DMH produces: asymmetry, that is, a right- (R- sided predominance in cardiac chronotropism, and lateralization, that is, a greater increase in ipsilateral renal sympathetic activity (RSNA. In the current study, we investigated whether excitatory amino acid (EAA receptors in the DMH-PAG pathway contribute to the functional interhemispheric difference. In urethane (1.2 to 1.4 g/kg, i.p. anesthetized rats, we observed that: (i nanoinjections of N-methyl D-aspartate (NMDA 100 pmol/100 nl into the unilateral DMH produced the same right-sided predominance in the control of cardiac chronotropy, (ii nanoinjections of NMDA into the ipsilateral DMH or PAG evoked lateralized RSNA responses, and (iii blockade of EAA receptors in the unilateral DMH attenuated the cardiovascular responses evoked by injection of NMDA into either the R- or left- (L- PAG. In awake rats, nanoinjection of kynurenic acid (1 nmol/100 nL into the L-DMH or R- or L-PAG attenuated the tachycardia evoked by air stress. However, the magnitude of stress-evoked tachycardia was smallest when the EAA receptors of the R-DMH were blocked. We conclude that EAA receptors contribute to the right-sided predominance in cardiac chronotropism. This interhemispheric difference that involves EAA receptors was observed in the DMH but not in the PAG.

  9. Excitatory amino acids in epilepsy and potential novel therapies.

    Science.gov (United States)

    Meldrum, B S

    1992-07-01

    Evidence that an abnormality of excitatory neurotransmission may contribute to the epileptic phenomena in various animal and human syndromes is reviewed. Altered glutamate transport or metabolism may be a contributory factor in some genetic syndromes and enhanced responsiveness to activation of NMDA receptors may be significant in various acquired forms of epilepsy. Decreasing glutamatergic neurotransmission provides a rational therapeutic approach to epilepsy. Potent anticonvulsant effects are seen with the acute administration of NMDA antagonists in a wide range of animal models. Some competitive antagonists acting at the NMDA/glutamate site show prolonged anticonvulsant activity following oral administration at doses free of motor side effects and appear suitable for clinical trial.

  10. Pain-related increase of excitatory transmission and decrease of inhibitory transmission in the central nucleus of the amygdala are mediated by mGluR1

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    Neugebauer Volker

    2010-12-01

    Full Text Available Abstract Neuroplasticity in the central nucleus of the amygdala (CeA, particularly its latero-capsular division (CeLC, is an important contributor to the emotional-affective aspects of pain. Previous studies showed synaptic plasticity of excitatory transmission to the CeLC in different pain models, but pain-related changes of inhibitory transmission remain to be determined. The CeLC receives convergent excitatory inputs from the parabrachial nucleus in the brainstem and from the basolateral amygdala (BLA. In addition, feedforward inhibition of CeA neurons is driven by glutamatergic projections from the BLA area to a cluster of GABAergic neurons in the intercalated cell masses (ITC. Using patch-clamp in rat brain slices we measured monosynaptic excitatory postsynaptic currents (EPSCs and polysynaptic inhibitory currents (IPSCs that were evoked by electrical stimulation in the BLA. In brain slices from arthritic rats, input-output functions of excitatory synaptic transmission were enhanced whereas inhibitory synaptic transmission was decreased compared to control slices from normal untreated rats. A non-NMDA receptor antagonist (NBQX blocked the EPSCs and reduced the IPSCs, suggesting that non-NMDA receptors mediate excitatory transmission and also contribute to glutamate-driven feed-forward inhibition of CeLC neurons. IPSCs were blocked by a GABAA receptor antagonist (bicuculline. Bicuculline increased EPSCs under normal conditions but not in slices from arthritic rats, which indicates a loss of GABAergic control of excitatory transmission. A metabotropic glutamate receptor subtype 1 (mGluR1 antagonist (LY367385 reversed both the increase of excitatory transmission and the decrease of inhibitory transmission in the arthritis pain model but had no effect on basal synaptic transmission in control slices from normal rats. The inhibitory effect of LY367385 on excitatory transmission was blocked by bicuculline suggesting the involvement of a GABAergic

  11. Population activity structure of excitatory and inhibitory neurons.

    Science.gov (United States)

    Bittner, Sean R; Williamson, Ryan C; Snyder, Adam C; Litwin-Kumar, Ashok; Doiron, Brent; Chase, Steven M; Smith, Matthew A; Yu, Byron M

    2017-01-01

    Many studies use population analysis approaches, such as dimensionality reduction, to characterize the activity of large groups of neurons. To date, these methods have treated each neuron equally, without taking into account whether neurons are excitatory or inhibitory. We studied population activity structure as a function of neuron type by applying factor analysis to spontaneous activity from spiking networks with balanced excitation and inhibition. Throughout the study, we characterized population activity structure by measuring its dimensionality and the percentage of overall activity variance that is shared among neurons. First, by sampling only excitatory or only inhibitory neurons, we found that the activity structures of these two populations in balanced networks are measurably different. We also found that the population activity structure is dependent on the ratio of excitatory to inhibitory neurons sampled. Finally we classified neurons from extracellular recordings in the primary visual cortex of anesthetized macaques as putative excitatory or inhibitory using waveform classification, and found similarities with the neuron type-specific population activity structure of a balanced network with excitatory clustering. These results imply that knowledge of neuron type is important, and allows for stronger statistical tests, when interpreting population activity structure.

  12. Population activity structure of excitatory and inhibitory neurons.

    Directory of Open Access Journals (Sweden)

    Sean R Bittner

    Full Text Available Many studies use population analysis approaches, such as dimensionality reduction, to characterize the activity of large groups of neurons. To date, these methods have treated each neuron equally, without taking into account whether neurons are excitatory or inhibitory. We studied population activity structure as a function of neuron type by applying factor analysis to spontaneous activity from spiking networks with balanced excitation and inhibition. Throughout the study, we characterized population activity structure by measuring its dimensionality and the percentage of overall activity variance that is shared among neurons. First, by sampling only excitatory or only inhibitory neurons, we found that the activity structures of these two populations in balanced networks are measurably different. We also found that the population activity structure is dependent on the ratio of excitatory to inhibitory neurons sampled. Finally we classified neurons from extracellular recordings in the primary visual cortex of anesthetized macaques as putative excitatory or inhibitory using waveform classification, and found similarities with the neuron type-specific population activity structure of a balanced network with excitatory clustering. These results imply that knowledge of neuron type is important, and allows for stronger statistical tests, when interpreting population activity structure.

  13. Population activity structure of excitatory and inhibitory neurons

    Science.gov (United States)

    Doiron, Brent

    2017-01-01

    Many studies use population analysis approaches, such as dimensionality reduction, to characterize the activity of large groups of neurons. To date, these methods have treated each neuron equally, without taking into account whether neurons are excitatory or inhibitory. We studied population activity structure as a function of neuron type by applying factor analysis to spontaneous activity from spiking networks with balanced excitation and inhibition. Throughout the study, we characterized population activity structure by measuring its dimensionality and the percentage of overall activity variance that is shared among neurons. First, by sampling only excitatory or only inhibitory neurons, we found that the activity structures of these two populations in balanced networks are measurably different. We also found that the population activity structure is dependent on the ratio of excitatory to inhibitory neurons sampled. Finally we classified neurons from extracellular recordings in the primary visual cortex of anesthetized macaques as putative excitatory or inhibitory using waveform classification, and found similarities with the neuron type-specific population activity structure of a balanced network with excitatory clustering. These results imply that knowledge of neuron type is important, and allows for stronger statistical tests, when interpreting population activity structure. PMID:28817581

  14. Purines released from astrocytes inhibit excitatory synaptic transmission in the ventral horn of the spinal cord

    DEFF Research Database (Denmark)

    Carlsen, Eva Maria Meier; Perrier, Jean-Francois Marie

    2014-01-01

    by different neuromodulators. These substances are usually thought of being released by dedicated neurons. However, in other networks from the central nervous system synaptic transmission is also modulated by transmitters released from astrocytes. The star-shaped glial cell responds to neurotransmitters....... Neurons responded to electrical stimulation by monosynaptic EPSCs (excitatory monosynaptic postsynaptic currents). We used mice expressing the enhanced green fluorescent protein under the promoter of the glial fibrillary acidic protein to identify astrocytes. Chelating calcium with BAPTA in a single...... neighboring astrocyte increased the amplitude of synaptic currents. In contrast, when we selectively stimulated astrocytes by activating PAR-1 receptors with the peptide TFLLR, the amplitude of EPSCs evoked by a paired stimulation protocol was reduced. The paired-pulse ratio was increased, suggesting...

  15. Effects of Ketamine on Neuronal Spontaneous Excitatory Postsynaptic Currents and Miniature Excitatory Postsynaptic Currents in the Somatosensory Cortex of Rats

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    Chengdong Yuan

    2016-07-01

    Full Text Available Background: Ketamine is a commonly used intravenous anesthetic which produces dissociation anesthesia, analgesia, and amnesia. The mechanism of ketamine-induced synaptic inhibition in high-level cortical areas is still unknown. We aimed to elucidate the effects of different concentrations of ketamine on the glutamatergic synaptic transmission of the neurons in the primary somatosensory cortex by using the whole-cell patch-clamp method. Methods: Sprague-Dawley rats (11–19 postnatal days, n=36 were used to obtain brain slices (300 μM. Spontaneous excitatory postsynaptic currents (data from 40 neurons were recorded at a command potential of -70 mV in the presence of bicuculline (a competitive antagonist of GABAA receptors, 30 μM and strychnine (glycine receptor antagonist, 30 μM. Miniature excitatory postsynaptic currents (data from 40 neurons were also recorded when 1 μM of tetrodotoxin was added into the artificial cerebrospinal fluid. We used GraphPad Prism5for statistical analysis. Significant differences in the mean amplitude and frequency were tested using the Student paired 2-tailed t test. Values of P<0.05 were considered significant. Results: Different concentrations of ketamine inhibited the frequency and amplitude of the spontaneous excitatory postsynaptic currents as well as the amplitude of the miniature excitatory postsynaptic currents in a concentration-dependent manner, but they exerted no significant effect on the frequency of the miniature excitatory postsynaptic currents. Conclusion: Ketamine inhibited the excitatory synaptic transmission of the neurons in the primary somatosensory cortex. The inhibition may have been mediated by a reduction in the sensitivity of the postsynaptic glutamatergic receptors.

  16. Infrared neural stimulation (INS) inhibits electrically evoked neural responses in the deaf white cat

    Science.gov (United States)

    Richter, Claus-Peter; Rajguru, Suhrud M.; Robinson, Alan; Young, Hunter K.

    2014-03-01

    Infrared neural stimulation (INS) has been used in the past to evoke neural activity from hearing and partially deaf animals. All the responses were excitatory. In Aplysia californica, Duke and coworkers demonstrated that INS also inhibits neural responses [1], which similar observations were made in the vestibular system [2, 3]. In deaf white cats that have cochleae with largely reduced spiral ganglion neuron counts and a significant degeneration of the organ of Corti, no cochlear compound action potentials could be observed during INS alone. However, the combined electrical and optical stimulation demonstrated inhibitory responses during irradiation with infrared light.

  17. Excitatory amino acid transmitters in epilepsy.

    Science.gov (United States)

    Meldrum, B S

    1991-01-01

    For the majority of human epilepsy syndromes, the molecular and cellular basis for the epileptic activity remains largely conjectural. The principal hypotheses currently concern: defects in membrane ionic conductances or transport mechanisms; defects in gamma-aminobutyric acid (GABA)-mediated inhibitory processes; and enhanced or abnormal excitatory synaptic action. Substantial evidence exists in humans and animals for acquired abnormalities in excitatory amino acid neurotransmission that may participate in the abnormal patterns of neuronal discharge, and this could provide the morphological basis for a recurrent excitatory pathway sustaining seizure discharges in temporal lobe epilepsy. In practice, two approaches appear significant in the suppression of seizures. One is to act postsynaptically on receptors to decrease the excitation induced by glutamate, and the other is to decrease synaptic release of glutamate and aspartate. Agents acting upon adenosine or GABAB receptors decrease glutamate release in vitro but do not have significant anticonvulsant activity, probably because of their predominant actions at other sites. Lamotrigine blocks stimulated release of glutamate and shows anticonvulsant activity in a wide range of animal models.

  18. Anatomical and pharmacological characterization of excitatory amino acid receptors

    International Nuclear Information System (INIS)

    Monaghan, D.T.

    1985-01-01

    The majority of the excitatory neurotransmission in the vertebrate Central Nervous System is thought to be mediated by acidic amino acid neurotransmitters. However, relatively little is known about the excitatory amino acid receptors and their distribution within the CNS. By analyzing radioligand binding to purified synaptic plasma membranes and to thin tissue sections processed for autoradiography, multiple distinct binding sites were found. These binding sites exhibited the pharmacological properties indicative of the excitatory amino acid receptors, which had been identified by electrophysiological techniques. Specifically, L-[ 3 H]-glutamate and D-[ 3 H]-amino-5-phosphonopentanoate appear to label N-methyl-D-aspartate receptors, L-[ 3 H]-glutamate and [ 3 H]-kainic acid appear to label kainic acid receptors, and L-[ 3 H]-glutamate and [ 3 H]-amino-3-hydroxy-5-methyl-4-isoxazolepropionate appear to label quisqualate receptors. Together, these results confirm the three receptor scheme proposed for excitatory amino acid neurotransmission. These results also show that these transmitter-receptor systems are differentially distributed in the brain, and that the total distribution is consistent with that found by other markers for excitatory amino acid-using neurons

  19. Visually Evoked 3-5 Hz Membrane Potential Oscillations Reduce the Responsiveness of Visual Cortex Neurons in Awake Behaving Mice.

    Science.gov (United States)

    Einstein, Michael C; Polack, Pierre-Olivier; Tran, Duy T; Golshani, Peyman

    2017-05-17

    Low-frequency membrane potential ( V m ) oscillations were once thought to only occur in sleeping and anesthetized states. Recently, low-frequency V m oscillations have been described in inactive awake animals, but it is unclear whether they shape sensory processing in neurons and whether they occur during active awake behavioral states. To answer these questions, we performed two-photon guided whole-cell V m recordings from primary visual cortex layer 2/3 excitatory and inhibitory neurons in awake mice during passive visual stimulation and performance of visual and auditory discrimination tasks. We recorded stereotyped 3-5 Hz V m oscillations where the V m baseline hyperpolarized as the V m underwent high amplitude rhythmic fluctuations lasting 1-2 s in duration. When 3-5 Hz V m oscillations coincided with visual cues, excitatory neuron responses to preferred cues were significantly reduced. Despite this disruption to sensory processing, visual cues were critical for evoking 3-5 Hz V m oscillations when animals performed discrimination tasks and passively viewed drifting grating stimuli. Using pupillometry and animal locomotive speed as indicators of arousal, we found that 3-5 Hz oscillations were not restricted to unaroused states and that they occurred equally in aroused and unaroused states. Therefore, low-frequency V m oscillations play a role in shaping sensory processing in visual cortical neurons, even during active wakefulness and decision making. SIGNIFICANCE STATEMENT A neuron's membrane potential ( V m ) strongly shapes how information is processed in sensory cortices of awake animals. Yet, very little is known about how low-frequency V m oscillations influence sensory processing and whether they occur in aroused awake animals. By performing two-photon guided whole-cell recordings from layer 2/3 excitatory and inhibitory neurons in the visual cortex of awake behaving animals, we found visually evoked stereotyped 3-5 Hz V m oscillations that disrupt

  20. Neonatal Nicotine Exposure Increases Excitatory Synaptic Transmission and Attenuates Nicotine-stimulated GABA release in the Adult Rat Hippocampus

    Science.gov (United States)

    Damborsky, Joanne C.; Griffith, William H.; Winzer-Serhan, Ursula H.

    2014-01-01

    Developmental exposure to nicotine has been linked to long-lasting changes in synaptic transmission which may contribute to behavioral abnormalities seen in offspring of women who smoke during pregnancy. Here, we examined the long-lasting effects of developmental nicotine exposure on glutamatergic and GABAergic neurotransmission, and on acute nicotine-induced glutamate and GABA release in the adult hippocampus, a structure important in cognitive and emotional behaviors. We utilized a chronic neonatal nicotine treatment model to administer nicotine (6 mg/kg/day) to rat pups from postnatal day (P) 1–7, a period that falls developmentally into the third human trimester. Using whole-cell voltage clamp recordings from CA1 pyramidal neurons in hippocampal slices, we measured excitatory and inhibitory postsynaptic currents in neonatally control- and nicotine-treated young adult males. Neonatal nicotine exposure significantly increased AMPA receptor-mediated spontaneous and evoked excitatory signaling, with no change in glutamate release probability in adults. Conversely, there was no increase in spontaneous GABAergic neurotransmission in nicotine-males. Chronic neonatal nicotine treatment had no effect on acute nicotine-stimulated glutamate release in adults, but acute nicotine-stimulated GABA release was significantly attenuated. Thus, neonatal nicotine exposure results in a persistent net increase in excitation and a concurrent loss of nicotinic acetylcholine receptor (nAChR)-mediated regulation of presynaptic GABA but not glutamate release, which would exacerbate excitation following endogenous or exogenous nAChR activation. Our data underscore an important role for nAChRs in hippocampal excitatory synapse development, and suggest selective long-term changes at specific presynaptic nAChRs which together could explain some of the behavioral abnormalities associated with maternal smoking. PMID:24950455

  1. mGluR1 receptors contribute to non-purinergic slow excitatory transmission to submucosal VIP neurons of guinea-pig ileum

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    Jaime Pei Pei Foong

    2009-05-01

    Full Text Available Vasoactive intestinal peptide (VIP immunoreactive secretomotor neurons in the submucous plexus are involved in mediating bacterial toxin-induced hypersecretion leading to diarrhoea. VIP neurons become hyperexcitable after the mucosa is exposed to cholera toxin, which suggests that the manipulation of the excitability of these neurons may be therapeutic. This study used standard intracellular recording methods to systematically characterize slow excitatory postsynaptic potentials (EPSPs evoked in submucosal VIP neurons by different stimulus regimes (1, 3 and 15 pulse 30 Hz stimulation, together with their associated input resistances and pharmacology. All slow EPSPs were associated with a significant increase in input resistance compared to baseline values. Slow EPSPs evoked by a single stimulus were confirmed to be purinergic, however, slow EPSPs evoked by 15 pulse trains were non-purinergic and those evoked by 3 pulse trains were mixed. NK1 or NK3 receptor antagonists did not affect slow EPSPs. The group I mGluR receptor antagonist, PHCCC reduced the amplitude of purinergic and non-purinergic slow EPSPs. Blocking mGluR1 receptors depressed the overall response to 3 and 15 pulse trains, but this effect was inconsistent, while blockade of mGluR5 receptors had no effect on the non-purinergic slow EPSPs. Thus, although other receptors are almost certainly involved, our data indicate that there are at least two pharmacologically distinct types of slow EPSPs in the VIP secretomotor neurons: one mediated by P2Y receptors and the other in part by mGluR1 receptors.

  2. Structural and Functional Alterations in Neocortical Circuits after Mild Traumatic Brain Injury

    Science.gov (United States)

    Vascak, Michal

    National concern over traumatic brain injury (TBI) is growing rapidly. Recent focus is on mild TBI (mTBI), which is the most prevalent injury level in both civilian and military demographics. A preeminent sequelae of mTBI is cognitive network disruption. Advanced neuroimaging of mTBI victims supports this premise, revealing alterations in activation and structure-function of excitatory and inhibitory neuronal systems, which are essential for network processing. However, clinical neuroimaging cannot resolve the cellular and molecular substrates underlying such changes. Therefore, to understand the full scope of mTBI-induced alterations it is necessary to study cortical networks on the microscopic level, where neurons form local networks that are the fundamental computational modules supporting cognition. Recently, in a well-controlled animal model of mTBI, we demonstrated in the excitatory pyramidal neuron system, isolated diffuse axonal injury (DAI), in concert with electrophysiological abnormalities in nearby intact (non-DAI) neurons. These findings were consistent with altered axon initial segment (AIS) intrinsic activity functionally associated with structural plasticity, and/or disturbances in extrinsic systems related to parvalbumin (PV)-expressing interneurons that form GABAergic synapses along the pyramidal neuron perisomatic/AIS domains. The AIS and perisomatic GABAergic synapses are domains critical for regulating neuronal activity and E-I balance. In this dissertation, we focus on the neocortical excitatory pyramidal neuron/inhibitory PV+ interneuron local network following mTBI. Our central hypothesis is that mTBI disrupts neuronal network structure and function causing imbalance of excitatory and inhibitory systems. To address this hypothesis we exploited transgenic and cre/lox mouse models of mTBI, employing approaches that couple state-of-the-art bioimaging with electrophysiology to determine the structuralfunctional alterations of excitatory and

  3. Irregular persistent activity induced by synaptic excitatory feedback

    Directory of Open Access Journals (Sweden)

    Francesca Barbieri

    2007-11-01

    Full Text Available Neurophysiological experiments on monkeys have reported highly irregular persistent activity during the performance of an oculomotor delayed-response task. These experiments show that during the delay period the coefficient of variation (CV of interspike intervals (ISI of prefrontal neurons is above 1, on average, and larger than during the fixation period. In the present paper, we show that this feature can be reproduced in a network in which persistent activity is induced by excitatory feedback, provided that (i the post-spike reset is close enough to threshold , (ii synaptic efficacies are a non-linear function of the pre-synaptic firing rate. Non-linearity between presynaptic rate and effective synaptic strength is implemented by a standard short-term depression mechanism (STD. First, we consider the simplest possible network with excitatory feedback: a fully connected homogeneous network of excitatory leaky integrate-and-fire neurons, using both numerical simulations and analytical techniques. The results are then confirmed in a network with selective excitatory neurons and inhibition. In both the cases there is a large range of values of the synaptic efficacies for which the statistics of firing of single cells is similar to experimental data.

  4. Contribution of NMDA receptor hypofunction in prefrontal and cortical excitatory neurons to schizophrenia-like phenotypes.

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    Gregory R Rompala

    Full Text Available Pharmacological and genetic studies support a role for NMDA receptor (NMDAR hypofunction in the etiology of schizophrenia. We have previously demonstrated that NMDAR obligatory subunit 1 (GluN1 deletion in corticolimbic interneurons during early postnatal development is sufficient to confer schizophrenia-like phenotypes in mice. However, the consequence of NMDAR hypofunction in cortical excitatory neurons is not well delineated. Here, we characterize a conditional knockout mouse strain (CtxGluN1 KO mice, in which postnatal GluN1 deletion is largely confined to the excitatory neurons in layer II/III of the medial prefrontal cortex and sensory cortices, as evidenced by the lack of GluN1 mRNA expression in in situ hybridization immunocytochemistry as well as the lack of NMDA currents with in vitro recordings. Mutants were impaired in prepulse inhibition of the auditory startle reflex as well as object-based short-term memory. However, they did not exhibit impairments in additional hallmarks of schizophrenia-like phenotypes (e.g. spatial working memory, social behavior, saccharine preference, novelty and amphetamine-induced hyperlocomotion, and anxiety-related behavior. Furthermore, upon administration of the NMDA receptor antagonist, MK-801, there were no differences in locomotor activity versus controls. The mutant mice also showed negligible levels of reactive oxygen species production following chronic social isolation, and recording of miniature-EPSC/IPSCs from layer II/III excitatory neurons in medial prefrontal cortex suggested no alteration in GABAergic activity. All together, the mutant mice displayed cognitive deficits in the absence of additional behavioral or cellular phenotypes reflecting schizophrenia pathophysiology. Thus, NMDAR hypofunction in prefrontal and cortical excitatory neurons may recapitulate only a cognitive aspect of human schizophrenia symptoms.

  5. Contribution of NMDA receptor hypofunction in prefrontal and cortical excitatory neurons to schizophrenia-like phenotypes.

    Science.gov (United States)

    Rompala, Gregory R; Zsiros, Veronika; Zhang, Shuqin; Kolata, Stefan M; Nakazawa, Kazu

    2013-01-01

    Pharmacological and genetic studies support a role for NMDA receptor (NMDAR) hypofunction in the etiology of schizophrenia. We have previously demonstrated that NMDAR obligatory subunit 1 (GluN1) deletion in corticolimbic interneurons during early postnatal development is sufficient to confer schizophrenia-like phenotypes in mice. However, the consequence of NMDAR hypofunction in cortical excitatory neurons is not well delineated. Here, we characterize a conditional knockout mouse strain (CtxGluN1 KO mice), in which postnatal GluN1 deletion is largely confined to the excitatory neurons in layer II/III of the medial prefrontal cortex and sensory cortices, as evidenced by the lack of GluN1 mRNA expression in in situ hybridization immunocytochemistry as well as the lack of NMDA currents with in vitro recordings. Mutants were impaired in prepulse inhibition of the auditory startle reflex as well as object-based short-term memory. However, they did not exhibit impairments in additional hallmarks of schizophrenia-like phenotypes (e.g. spatial working memory, social behavior, saccharine preference, novelty and amphetamine-induced hyperlocomotion, and anxiety-related behavior). Furthermore, upon administration of the NMDA receptor antagonist, MK-801, there were no differences in locomotor activity versus controls. The mutant mice also showed negligible levels of reactive oxygen species production following chronic social isolation, and recording of miniature-EPSC/IPSCs from layer II/III excitatory neurons in medial prefrontal cortex suggested no alteration in GABAergic activity. All together, the mutant mice displayed cognitive deficits in the absence of additional behavioral or cellular phenotypes reflecting schizophrenia pathophysiology. Thus, NMDAR hypofunction in prefrontal and cortical excitatory neurons may recapitulate only a cognitive aspect of human schizophrenia symptoms.

  6. Recording visual evoked potentials and auditory evoked P300 at 9.4T static magnetic field.

    Science.gov (United States)

    Arrubla, Jorge; Neuner, Irene; Hahn, David; Boers, Frank; Shah, N Jon

    2013-01-01

    Simultaneous recording of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) has shown a number of advantages that make this multimodal technique superior to fMRI alone. The feasibility of recording EEG at ultra-high static magnetic field up to 9.4 T was recently demonstrated and promises to be implemented soon in fMRI studies at ultra high magnetic fields. Recording visual evoked potentials are expected to be amongst the most simple for simultaneous EEG/fMRI at ultra-high magnetic field due to the easy assessment of the visual cortex. Auditory evoked P300 measurements are of interest since it is believed that they represent the earliest stage of cognitive processing. In this study, we investigate the feasibility of recording visual evoked potentials and auditory evoked P300 in a 9.4 T static magnetic field. For this purpose, EEG data were recorded from 26 healthy volunteers inside a 9.4 T MR scanner using a 32-channel MR compatible EEG system. Visual stimulation and auditory oddball paradigm were presented in order to elicit evoked related potentials (ERP). Recordings made outside the scanner were performed using the same stimuli and EEG system for comparison purposes. We were able to retrieve visual P100 and auditory P300 evoked potentials at 9.4 T static magnetic field after correction of the ballistocardiogram artefact using independent component analysis. The latencies of the ERPs recorded at 9.4 T were not different from those recorded at 0 T. The amplitudes of ERPs were higher at 9.4 T when compared to recordings at 0 T. Nevertheless, it seems that the increased amplitudes of the ERPs are due to the effect of the ultra-high field on the EEG recording system rather than alteration in the intrinsic processes that generate the electrophysiological responses.

  7. IGF-1 Receptor Differentially Regulates Spontaneous and Evoked Transmission via Mitochondria at Hippocampal Synapses

    Science.gov (United States)

    Gazit, Neta; Vertkin, Irena; Shapira, Ilana; Helm, Martin; Slomowitz, Edden; Sheiba, Maayan; Mor, Yael; Rizzoli, Silvio; Slutsky, Inna

    2016-01-01

    Summary The insulin-like growth factor-1 receptor (IGF-1R) signaling is a key regulator of lifespan, growth, and development. While reduced IGF-1R signaling delays aging and Alzheimer’s disease progression, whether and how it regulates information processing at central synapses remains elusive. Here, we show that presynaptic IGF-1Rs are basally active, regulating synaptic vesicle release and short-term plasticity in excitatory hippocampal neurons. Acute IGF-1R blockade or transient knockdown suppresses spike-evoked synaptic transmission and presynaptic cytosolic Ca2+ transients, while promoting spontaneous transmission and resting Ca2+ level. This dual effect on transmitter release is mediated by mitochondria that attenuate Ca2+ buffering in the absence of spikes and decrease ATP production during spiking activity. We conclude that the mitochondria, activated by IGF-1R signaling, constitute a critical regulator of information processing in hippocampal neurons by maintaining evoked-to-spontaneous transmission ratio, while constraining synaptic facilitation at high frequencies. Excessive IGF-1R tone may contribute to hippocampal hyperactivity associated with Alzheimer’s disease. Video Abstract PMID:26804996

  8. Roles of N-methyl-d-aspartate receptors during the sensory stimulation-evoked field potential responses in mouse cerebellar cortical molecular layer.

    Science.gov (United States)

    Xu, Yin-Hua; Zhang, Guang-Jian; Zhao, Jing-Tong; Chu, Chun-Ping; Li, Yu-Zi; Qiu, De-Lai

    2017-11-01

    The functions of N-methyl-d-aspartate receptors (NMDARs) in cerebellar cortex have been widely studied under in vitro condition, but their roles during the sensory stimulation-evoked responses in the cerebellar cortical molecular layer in living animals are currently unclear. We here investigated the roles of NMDARs during the air-puff stimulation on ipsilateral whisker pad-evoked field potential responses in cerebellar cortical molecular layer in urethane-anesthetized mice by electrophysiological recording and pharmacological methods. Our results showed that cerebellar surface administration of NMDA induced a dose-dependent decrease in amplitude of the facial stimulation-evoked inhibitory responses (P1) in the molecular layer, accompanied with decreases in decay time, half-width and area under curve (AUC) of P1. The IC 50 of NMDA induced inhibition in amplitude of P1 was 46.5μM. In addition, application of NMDA induced significant increases in the decay time, half-width and AUC values of the facial stimulation-evoked excitatory responses (N1) in the molecular layer. Application of an NMDAR blocker, D-APV (250μM) abolished the facial stimulation-evoked P1 in the molecular layer. These results suggested that NMDARs play a critical role during the sensory information processing in cerebellar cortical molecular layer in vivo in mice. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Single-sweep spectral analysis of contact heat evoked potentials

    DEFF Research Database (Denmark)

    Hansen, Tine M; Graversen, Carina; Frøkjaer, Jens B

    2015-01-01

    AIMS: The cortical response to nociceptive thermal stimuli recorded as contact heat evoked potentials (CHEPs) may be altered by morphine. However, previous studies have averaged CHEPs over multiple stimuli, which are confounded by jitter between sweeps. Thus, the aim was to assess single-sweep ch......AIMS: The cortical response to nociceptive thermal stimuli recorded as contact heat evoked potentials (CHEPs) may be altered by morphine. However, previous studies have averaged CHEPs over multiple stimuli, which are confounded by jitter between sweeps. Thus, the aim was to assess single...... by 13% (P = 0.04) and 9% (P = 0.007), while the beta and gamma bands were increased by 10% (P = 0.006) and 24% (P = 0.04). CONCLUSION: The decreases in the delta and theta band are suggested to represent a decrease in the pain specific morphology of the CHEPs, which indicates a diminished pain response...

  10. Excitatory Neuronal Hubs Configure Multisensory Integration of Slow Waves in Association Cortex

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    Satoshi Kuroki

    2018-03-01

    Full Text Available Summary: Multisensory integration (MSI is a fundamental emergent property of the mammalian brain. During MSI, perceptual information encoded in patterned activity is processed in multimodal association cortex. The systems-level neuronal dynamics that coordinate MSI, however, are unknown. Here, we demonstrate intrinsic hub-like network activity in the association cortex that regulates MSI. We engineered calcium reporter mouse lines based on the fluorescence resonance energy transfer sensor yellow cameleon (YC2.60 expressed in excitatory or inhibitory neurons. In medial and parietal association cortex, we observed spontaneous slow waves that self-organized into hubs defined by long-range excitatory and local inhibitory circuits. Unlike directional source/sink-like flows in sensory areas, medial/parietal excitatory and inhibitory hubs had net-zero balanced inputs. Remarkably, multisensory stimulation triggered rapid phase-locking mainly of excitatory hub activity persisting for seconds after the stimulus offset. Therefore, association cortex tends to form balanced excitatory networks that configure slow-wave phase-locking for MSI. Video Abstract: : Kuroki et al. performed cell-type-specific, wide-field FRET-based calcium imaging to visualize cortical network activity induced by multisensory inputs. They observed phase-locking of cortical slow waves in excitatory neuronal hubs in association cortical areas that may underlie multisensory integration. Keywords: wide-field calcium imaging, multisensory integration, cortical slow waves, association cortex, phase locking, fluorescence resonance energy transfer, spontaneous activity, excitatory neuron, inhibitory neuron, mouse

  11. Excitatory amino acid neurotoxicity and neurodegenerative disease.

    Science.gov (United States)

    Meldrum, B; Garthwaite, J

    1990-09-01

    The progress over the last 30 years in defining the role of excitatory amino acids in normal physiological function and in the abnormal neuronal activity of epilepsy has been reviewed in earlier articles in this series. In the last five years it has become clear that excitatory amino acids also play a role in a wide range of neurodegenerative processes. The evidence is clearest where the degenerative process is acute, but is more controversial for slow degenerative processes. In this article Brian Meldrum and John Garthwaite review in vivo and in vitro studies of the cytotoxicity of amino acids and summarize the contribution of such toxicity to acute and chronic neurodegenerative disorders.

  12. Computer simulations of neural mechanisms explaining upper and lower limb excitatory neural coupling

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    Ferris Daniel P

    2010-12-01

    Full Text Available Abstract Background When humans perform rhythmic upper and lower limb locomotor-like movements, there is an excitatory effect of upper limb exertion on lower limb muscle recruitment. To investigate potential neural mechanisms for this behavioral observation, we developed computer simulations modeling interlimb neural pathways among central pattern generators. We hypothesized that enhancement of muscle recruitment from interlimb spinal mechanisms was not sufficient to explain muscle enhancement levels observed in experimental data. Methods We used Matsuoka oscillators for the central pattern generators (CPG and determined parameters that enhanced amplitudes of rhythmic steady state bursts. Potential mechanisms for output enhancement were excitatory and inhibitory sensory feedback gains, excitatory and inhibitory interlimb coupling gains, and coupling geometry. We first simulated the simplest case, a single CPG, and then expanded the model to have two CPGs and lastly four CPGs. In the two and four CPG models, the lower limb CPGs did not receive supraspinal input such that the only mechanisms available for enhancing output were interlimb coupling gains and sensory feedback gains. Results In a two-CPG model with inhibitory sensory feedback gains, only excitatory gains of ipsilateral flexor-extensor/extensor-flexor coupling produced reciprocal upper-lower limb bursts and enhanced output up to 26%. In a two-CPG model with excitatory sensory feedback gains, excitatory gains of contralateral flexor-flexor/extensor-extensor coupling produced reciprocal upper-lower limb bursts and enhanced output up to 100%. However, within a given excitatory sensory feedback gain, enhancement due to excitatory interlimb gains could only reach levels up to 20%. Interconnecting four CPGs to have ipsilateral flexor-extensor/extensor-flexor coupling, contralateral flexor-flexor/extensor-extensor coupling, and bilateral flexor-extensor/extensor-flexor coupling could enhance

  13. Neuronal Rac1 Is Required for Learning-Evoked Neurogenesis

    Science.gov (United States)

    Anderson, Matthew P.; Freewoman, Julia; Cord, Branden; Babu, Harish; Brakebusch, Cord

    2013-01-01

    Hippocampus-dependent learning and memory relies on synaptic plasticity as well as network adaptations provided by the addition of adult-born neurons. We have previously shown that activity-induced intracellular signaling through the Rho family small GTPase Rac1 is necessary in forebrain projection neurons for normal synaptic plasticity in vivo, and here we show that selective loss of neuronal Rac1 also impairs the learning-evoked increase in neurogenesis in the adult mouse hippocampus. Earlier work has indicated that experience elevates the abundance of adult-born neurons in the hippocampus primarily by enhancing the survival of neurons produced just before the learning event. Loss of Rac1 in mature projection neurons did reduce learning-evoked neurogenesis but, contrary to our expectations, these effects were not mediated by altering the survival of young neurons in the hippocampus. Instead, loss of neuronal Rac1 activation selectively impaired a learning-evoked increase in the proliferation and accumulation of neural precursors generated during the learning event itself. This indicates that experience-induced alterations in neurogenesis can be mechanistically resolved into two effects: (1) the well documented but Rac1-independent signaling cascade that enhances the survival of young postmitotic neurons; and (2) a previously unrecognized Rac1-dependent signaling cascade that stimulates the proliferative production and retention of new neurons generated during learning itself. PMID:23884931

  14. Excitatory amino acid transporters: recent insights into molecular mechanisms, novel modes of modulation and new therapeutic possibilities

    DEFF Research Database (Denmark)

    Jensen, Anders A.; Fahlke, Christoph; Bjørn-Yoshimoto, Walden Emil

    2015-01-01

    The five excitatory amino acid transporters (EAAT1–5) mediating the synaptic uptake of the major excitatory neurotransmitter glutamate are differently expressed throughout the CNS and at the synaptic level. Although EAATs are crucial for normal excitatory neurotransmission, explorations into the ......The five excitatory amino acid transporters (EAAT1–5) mediating the synaptic uptake of the major excitatory neurotransmitter glutamate are differently expressed throughout the CNS and at the synaptic level. Although EAATs are crucial for normal excitatory neurotransmission, explorations...

  15. SynDIG4/Prrt1 Is Required for Excitatory Synapse Development and Plasticity Underlying Cognitive Function

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    Lucas Matt

    2018-02-01

    Full Text Available Altering AMPA receptor (AMPAR content at synapses is a key mechanism underlying the regulation of synaptic strength during learning and memory. Previous work demonstrated that SynDIG1 (synapse differentiation-induced gene 1 encodes a transmembrane AMPAR-associated protein that regulates excitatory synapse strength and number. Here we show that the related protein SynDIG4 (also known as Prrt1 modifies AMPAR gating properties in a subunit-dependent manner. Young SynDIG4 knockout (KO mice have weaker excitatory synapses, as evaluated by immunocytochemistry and electrophysiology. Adult SynDIG4 KO mice show complete loss of tetanus-induced long-term potentiation (LTP, while mEPSC amplitude is reduced by only 25%. Furthermore, SynDIG4 KO mice exhibit deficits in two independent cognitive assays. Given that SynDIG4 colocalizes with the AMPAR subunit GluA1 at non-synaptic sites, we propose that SynDIG4 maintains a pool of extrasynaptic AMPARs necessary for synapse development and function underlying higher-order cognitive plasticity.

  16. Genetic targeting of NRXN2 in mice unveils role in excitatory cortical synapse function and social behaviors

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    Gesche eBorn

    2015-02-01

    Full Text Available Human genetics has identified rare copy number variations and deleterious mutations for all neurexin genes (NRXN1-3 in patients with neurodevelopmental diseases, and electrophysiological recordings in animal brains have shown that Nrxns are important for synaptic transmission. While several mouse models for Nrxn1α inactivation have previously been studied for behavioral changes, very little information is available for other variants. Here, we validate that mice lacking Nrxn2α exhibit behavioral abnormalities, characterized by social interaction deficits and increased anxiety-like behavior, which partially overlap, partially differ from Nrxn1α mutant behaviors. Using patch-clamp recordings in Nrxn2α knockout brains, we observe reduced spontaneous transmitter release at excitatory synapses in the neocortex. We also analyse at this cellular level a novel NRXN2 mouse model that carries a combined deletion of Nrxn2α and Nrxn2β. Electrophysiological analysis of this Nrxn2-mutant mouse shows surprisingly similar defects of excitatory release to Nrxn2α, indicating that the β-variant of Nrxn2 has no strong function in basic transmission at these synapses. Inhibitory transmission as well as synapse densities and ultrastructure remain unchanged in the neocortex of both models. Furthermore, at Nrxn2α and Nrxn2-mutant excitatory synapses we find an altered facilitation and N-methyl-D-aspartate receptor (NMDAR function because NMDAR-dependent decay time and NMDAR-mediated responses are reduced. As Nrxn can indirectly be linked to NMDAR via neuroligin and PSD-95, the trans-synaptic nature of this complex may help to explain occurrence of presynaptic and postsynaptic effects. Since excitatory/inhibitory imbalances and impairment of NMDAR function are alledged to have a role in autism and schizophrenia, our results support the idea of a related pathomechanism in these disorders.

  17. Role for excitatory amino acids in methamphetamine-induced nigrostriatal dopaminergic toxicity.

    Science.gov (United States)

    Sonsalla, P K; Nicklas, W J; Heikkila, R E

    1989-01-20

    The systemic administration of either methamphetamine or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to experimental animals produces degenerative changes in nigrostriatal dopaminergic neurons or their axon terminals. This study was conducted to determine if excitatory amino acids, which appear to be involved in various neurodegenerative disorders, might also contribute to the dopaminergic neurotoxicity produced in mice by either methamphetamine or MPTP. MK-801, phencyclidine, and ketamine, noncompetitive antagonists of one subtype of excitatory amino acid receptor, the N-methyl-D-aspartate receptor, provided substantial protection against neurotoxicity produced by methamphetamine but not that produced by MPTP. These findings indicate that excitatory amino acids play an important role in the nigrostriatal dopaminergic damage induced by methamphetamine.

  18. Evoked potentials in pediatric cerebral malaria

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    Minal Bhanushali

    2011-12-01

    Full Text Available Cortical evoked potentials (EP provide localized data regarding brain function and may offer prognostic information and insights into the pathologic mechanisms of malariamediated cerebral injury. As part of a prospective cohort study, we obtained somatosensory evoked potentials (SSEPs and brainstem auditory EPs (AEPs within 24 hours of admission on 27 consecutive children admitted with cerebral malaria (CM. Children underwent follow-up for 12 months to determine if they had any long term neurologic sequelae. EPs were obtained in 27 pediatric CM admissions. Two children died. Among survivors followed an average of 514 days, 7/25 (28.0% had at least one adverse neurologic outcome. Only a single subject had absent cortical EPs on admission and this child had a good neurologic outcome. Among pediatric CM survivors, cortical EPs are generally intact and do not predict adverse neurologic outcomes. Further study is needed to determine if alterations in cortical EPs can be used to predict a fatal outcome in CM.

  19. Scent-evoked nostalgia.

    Science.gov (United States)

    Reid, Chelsea A; Green, Jeffrey D; Wildschut, Tim; Sedikides, Constantine

    2015-01-01

    Can scents evoke nostalgia; what might be the psychological implications of such an evocation? Participants sampled 12 scents and rated the extent to which each scent was familiar, arousing and autobiographically relevant, as well as the extent to which each scent elicited nostalgia. Participants who were high (compared to low) in nostalgia proneness reported more scent-evoked nostalgia, and scents elicited greater nostalgia to the extent that they were arousing, familiar and autobiographically relevant. Scent-evoked nostalgia predicted higher levels of positive affect, self-esteem, self-continuity, optimism, social connectedness and meaning in life. In addition, scent-evoked nostalgia was characterised by more positive emotions than either non-nostalgic autobiographical memories or non-nostalgic non-autobiographical memories. Finally, scent-evoked nostalgia predicted in-the-moment feelings of personal (general or object-specific) nostalgia. The findings represent a foray into understanding the triggers and affective signature of scent-evoked nostalgia.

  20. Bottom-up driven involuntary auditory evoked field change: constant sound sequencing amplifies but does not sharpen neural activity.

    Science.gov (United States)

    Okamoto, Hidehiko; Stracke, Henning; Lagemann, Lothar; Pantev, Christo

    2010-01-01

    The capability of involuntarily tracking certain sound signals during the simultaneous presence of noise is essential in human daily life. Previous studies have demonstrated that top-down auditory focused attention can enhance excitatory and inhibitory neural activity, resulting in sharpening of frequency tuning of auditory neurons. In the present study, we investigated bottom-up driven involuntary neural processing of sound signals in noisy environments by means of magnetoencephalography. We contrasted two sound signal sequencing conditions: "constant sequencing" versus "random sequencing." Based on a pool of 16 different frequencies, either identical (constant sequencing) or pseudorandomly chosen (random sequencing) test frequencies were presented blockwise together with band-eliminated noises to nonattending subjects. The results demonstrated that the auditory evoked fields elicited in the constant sequencing condition were significantly enhanced compared with the random sequencing condition. However, the enhancement was not significantly different between different band-eliminated noise conditions. Thus the present study confirms that by constant sound signal sequencing under nonattentive listening the neural activity in human auditory cortex can be enhanced, but not sharpened. Our results indicate that bottom-up driven involuntary neural processing may mainly amplify excitatory neural networks, but may not effectively enhance inhibitory neural circuits.

  1. Altered Evoked Gamma-Band Responses Reveal Impaired Early Visual Processing in ADHD Children

    Science.gov (United States)

    Lenz, Daniel; Krauel, Kerstin; Flechtner, Hans-Henning; Schadow, Jeanette; Hinrichs, Hermann; Herrmann, Christoph S.

    2010-01-01

    Neurophysiological studies yield contrary results whether attentional problems of patients with attention-deficit/hyperactivity disorder (ADHD) are related to early visual processing deficits or not. Evoked gamma-band responses (GBRs), being among the first cortical responses occurring as early as 90 ms after visual stimulation in human EEG, have…

  2. Spatial distribution of excitatory synapses on the dendrites of ganglion cells in the mouse retina.

    Directory of Open Access Journals (Sweden)

    Yin-Peng Chen

    Full Text Available Excitatory glutamatergic inputs from bipolar cells affect the physiological properties of ganglion cells in the mammalian retina. The spatial distribution of these excitatory synapses on the dendrites of retinal ganglion cells thus may shape their distinct functions. To visualize the spatial pattern of excitatory glutamatergic input into the ganglion cells in the mouse retina, particle-mediated gene transfer of plasmids expressing postsynaptic density 95-green fluorescent fusion protein (PSD95-GFP was used to label the excitatory synapses. Despite wide variation in the size and morphology of the retinal ganglion cells, the expression of PSD95 puncta was found to follow two general rules. Firstly, the PSD95 puncta are regularly spaced, at 1-2 µm intervals, along the dendrites, whereby the presence of an excitatory synapse creates an exclusion zone that rules out the presence of other glutamatergic synaptic inputs. Secondly, the spatial distribution of PSD95 puncta on the dendrites of diverse retinal ganglion cells are similar in that the number of excitatory synapses appears to be less on primary dendrites and to increase to a plateau on higher branch order dendrites. These observations suggest that synaptogenesis is spatially regulated along the dendritic segments and that the number of synaptic contacts is relatively constant beyond the primary dendrites. Interestingly, we also found that the linear puncta density is slightly higher in large cells than in small cells. This may suggest that retinal ganglion cells with a large dendritic field tend to show an increased connectivity of excitatory synapses that makes up for their reduced dendrite density. Mapping the spatial distribution pattern of the excitatory synapses on retinal ganglion cells thus provides explicit structural information that is essential for our understanding of how excitatory glutamatergic inputs shape neuronal responses.

  3. Excitatory amino acid receptor blockade within the caudal pressor area and rostral ventrolateral medulla alters cardiovascular responses to nucleus raphe obscurus stimulation in rats

    Directory of Open Access Journals (Sweden)

    Silva N.F.

    2002-01-01

    Full Text Available Pressor responses elicited by stimulation of the nucleus raphe obscurus (NRO depend on the integrity of the rostral ventrolateral medulla (RVLM. Therefore, to test the participation of excitatory amino acid (EAA receptors in the cardiovascular responses evoked by NRO stimulation (1 ms, 100 Hz, 40-70 µA, for 10 s, the EAA antagonist kynurenic acid (Kyn was microinjected at different sites in the ventrolateral medullar surface (2.7 nmol/200 nl of male Wistar rats (270-320 g, N = 39 and NRO stimulation was repeated. The effects of NRO stimulation were: hypertension (deltaMAP = +43 ± 1 mmHg, P<0.01, bradycardia (deltaHR = -30 ± 7 bpm, P<0.01 and apnea. Bilateral microinjection of Kyn into the RVLM, which did not change baseline parameters, almost abolished the bradycardia induced by NRO stimulation (deltaHR = -61 ± 3 before vs -2 ± 3 bpm after Kyn, P<0.01, N = 7. Unilateral microinjection of Kyn into the CVLM did not change baseline parameters or reduce the pressor response to NRO stimulation (deltaMAP = +46 ± 5 before vs +48 ± 5 mmHg after Kyn, N = 6. Kyn bilaterally microinjected into the caudal pressor area reduced blood pressure and heart rate and almost abolished the pressor response to NRO stimulation (deltaMAP = +46 ± 4 mmHg before vs +4 ± 2 mmHg after Kyn, P<0.01, N = 7. These results indicate that EAA receptors on the medullary ventrolateral surface play a role in the modulation of the cardiovascular responses induced by NRO stimulation, and also suggest that the RVLM participates in the modulation of heart rate responses and that the caudal pressor area modulates the pressor response following NRO stimulation.

  4. Degree of synchronization modulated by inhibitory neurons in clustered excitatory-inhibitory recurrent networks

    Science.gov (United States)

    Li, Huiyan; Sun, Xiaojuan; Xiao, Jinghua

    2018-01-01

    An excitatory-inhibitory recurrent neuronal network is established to numerically study the effect of inhibitory neurons on the synchronization degree of neuronal systems. The obtained results show that, with the number of inhibitory neurons and the coupling strength from an inhibitory neuron to an excitatory neuron increasing, inhibitory neurons can not only reduce the synchronization degree when the synchronization degree of the excitatory population is initially higher, but also enhance it when it is initially lower. Meanwhile, inhibitory neurons could also help the neuronal networks to maintain moderate synchronized states. In this paper, we call this effect as modulation effect of inhibitory neurons. With the obtained results, it is further revealed that the ratio of excitatory neurons to inhibitory neurons being nearly 4 : 1 is an economic and affordable choice for inhibitory neurons to realize this modulation effect.

  5. Effect of calcium on excitatory neuromuscular transmission in the crayfish

    Science.gov (United States)

    Bracho, H.; Orkand, R. K.

    1970-01-01

    1. The effects of varying the external Ca concentration from 1·8 to 30 mM/l. (⅛-2 times normal) have been studied at the in vitro crayfish excitatory neuromuscular junction. Electrophysiological techniques were used to record transmembrane junctional potentials from muscle fibres and extracellular junctional currents from the vicinity of nerve terminals. 2. The excitatory junctional potential amplitude was proportional to [Ca]0n, where n varied between 0·68 and 0·94 (mean 0·82) when [Ca]0 was varied from 1·8 to 15 mM/l. 3. The increase in junctional potential amplitude on raising [Ca]0 resulted primarily from an increase in the average number of quanta of excitatory transmitter released from the presynaptic nerve terminal by the nerve impulse. 4. The size of the quanta, synaptic delay, presynaptic potential and electrical properties of the muscle membrane were little affected by changes in calcium concentration in the range studied. PMID:5498460

  6. Excitatory components of the mammalian locomotor CPG

    DEFF Research Database (Denmark)

    Kiehn, Ole; Quinlan, Katharina A.; Restrepo, Carlos Ernesto

    2008-01-01

    Locomotion in mammals is to a large degree controlled directly by intrinsic spinal networks, called central pattern generators (CPGs). The overall function of these networks is governed by interaction between inhibitory and excitatory neurons. In the present review, we will discuss recent finding...

  7. Astrocyte matricellular proteins that control excitatory synaptogenesis are regulated by inflammatory cytokines and correlate with paralysis severity during experimental autoimmune encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Pennelope K. Blakely

    2015-10-01

    Full Text Available The matricellular proteins, secreted protein acidic and rich in cysteine (SPARC and SPARC-like 1 (SPARCL1, are produced by astrocytes and control excitatory synaptogenesis in the central nervous system. While SPARCL1 directly promotes excitatory synapse formation in vitro and in the developing nervous system in vivo, SPARC specifically antagonizes the synaptogenic actions of SPARCL1. We hypothesized these proteins also help maintain existing excitatory synapses in adult hosts, and that local inflammation in the spinal cord alters their production in a way that dynamically modulates motor synapses and impacts the severity of paralysis during experimental autoimmune encephalomyelitis (EAE in mice. Using a spontaneously remitting EAE model, paralysis severity correlated inversely with both expression of synaptic proteins and the number of synapses in direct contact with the perikarya of motor neurons in spinal grey matter. In both remitting and non-remitting EAE models, paralysis severity also correlated inversely with sparcl1:sparc transcript and SPARCL1:SPARC protein ratios directly in lumbar spinal cord tissue. In vitro, astrocyte production of both SPARCL1 and SPARC was regulated by T cell-derived cytokines, causing dynamic modulation of the SPARCL1:SPARC expression ratio. Taken together, these data support a model whereby proinflammatory cytokines inhibit SPARCL1 and/or augment SPARC expression by astrocytes in spinal grey matter that, in turn, cause either transient or sustained synaptic retraction from lumbar spinal motor neurons thereby regulating hind limb paralysis during EAE. Ongoing studies seek ways to alter this SPARCL1:SPARC expression ratio in favor of synapse reformation/maintenance and thus help to modulate neurologic deficits during times of inflammation. This could identify new astrocyte-targeted therapies for diseases such as multiple sclerosis.

  8. Normalization reduces intersubject variability in cervical vestibular evoked myogenic potentials.

    Science.gov (United States)

    van Tilburg, Mark J; Herrmann, Barbara S; Guinan, John J; Rauch, Steven D

    2014-09-01

    Cervical vestibular evoked myogenic potentials are used to assess saccular and inferior vestibular nerve function. Normalization of the VEMP waveform has been proposed to reduce the variability in vestibular evoked myogenic potentials by correcting for muscle activation. In this study, we test the hypothesis that normalization of the raw cervical VEMP waveform causes a significant decrease in the intersubject variability. Prospective cohort study. Large specialty hospital, department of otolaryngology. Twenty healthy subjects were used in this study. All subjects underwent cervical vestibular evoked myogenic potential testing using short tone bursts at 250, 500, 750, and 1,000 Hz. Both intersubject and intrasubject variability was assessed. Variability between raw and normalized peak-to-peak amplitudes was compared using the coefficient of variation. Intrasubject variability was assessed using the intraclass correlation coefficient and interaural asymmetry ratio. cVEMPs were present in most ears. Highest peak-to-peak amplitudes were recorded at 750 Hz. Normalization did not alter cVEMP tuning characteristics. Normalization of the cVEMP response caused a significant reduction in intersubject variability of the peak-to-peak amplitude. No significant change was seen in the intrasubject variability. Normalization significantly reduces cVEMP intersubject variability in healthy subjects without altering cVEMP characteristics. By reducing cVEMP amplitude variation due to nonsaccular, muscle-related factors, cVEMP normalization is expected to improve the ability to distinguish between healthy and pathologic responses in the clinical application of cVEMP testing.

  9. Do personality traits predict individual differences in excitatory and inhibitory learning?

    Directory of Open Access Journals (Sweden)

    Zhimin eHe

    2013-05-01

    Full Text Available Conditioned inhibition (CI is demonstrated in classical conditioning when a stimulus is used to signal the omission of an otherwise expected outcome. This basic learning ability is involved in a wide range of normal behaviour - and thus its disruption could produce a correspondingly wide range of behavioural deficits. The present study employed a computer-based task to measure conditioned excitation and inhibition in the same discrimination procedure. Conditioned inhibition by summation test was clearly demonstrated. Additionally summary measures of excitatory and inhibitory learning (difference scores were calculated in order to explore how performance related to individual differences in a large sample of normal participants (n=176 following exclusion of those not meeting the basic learning criterion. The individual difference measures selected derive from two biologically-based personality theories, Gray’s reinforcement sensitivity theory (1982 and Eysenck’s psychoticism, extraversion and neuroticism theory (1991. Following the behavioural tasks, participants completed the behavioural inhibition system/behavioural activation system scales (BIS/BAS and the Eysenck personality questionnaire revised short scale (EPQ-RS. Analyses of the relationship between scores on each of the scales and summary measures of excitatory and inhibitory learning suggested that those with higher BAS (specifically the drive sub-scale and higher EPQ-RS neuroticism showed reduced levels of excitatory conditioning. Inhibitory conditioning was similarly attenuated in those with higher EPQ-RS neuroticism, as well as in those with higher BIS scores. Thus the findings are consistent with higher levels of neuroticism being accompanied by generally impaired associative learning, both inhibitory and excitatory. There was also evidence for some dissociation in the effects of behavioural activation and behavioural inhibition on excitatory and inhibitory learning respectively.

  10. The anticonvulsant action of the galanin receptor agonist NAX-5055 involves modulation of both excitatory- and inhibitory neurotransmission

    DEFF Research Database (Denmark)

    Walls, Anne B; Flynn, Sean P; West, Peter J

    2016-01-01

    -based anti-convulsant drugs was prompted. Based on this, a rationally designed GalR1 preferring galanin analogue, NAX-5055, was synthesized. This compound demonstrates anti-convulsant actions in several animal models of epilepsy. However, the alterations at the cellular level leading to this anti......-convulsant action of NAX-5055 are not known. Here we investigate the action of NAX-5055 at the cellular level by determining its effects on excitatory and inhibitory neurotransmission, i.e. vesicular release of glutamate and GABA, respectively, in cerebellar, neocortical and hippocampal preparations. In addition...

  11. Electrical field stimulation-induced excitatory responses of ...

    African Journals Online (AJOL)

    effect of the endothelium on electrical field stimulation (EFS)-induced excitatory responses of pulmonary artery segments from pulmonary hypertensive rats. Methods: Pulmonary hypertension was induced in rats with a single dose of monocrotaline (60 mg/kg) and 21 days later, arterial rings were set up for isometric tension ...

  12. Sequential dynamics in the motif of excitatory coupled elements

    Science.gov (United States)

    Korotkov, Alexander G.; Kazakov, Alexey O.; Osipov, Grigory V.

    2015-11-01

    In this article a new model of motif (small ensemble) of neuron-like elements is proposed. It is built with the use of the generalized Lotka-Volterra model with excitatory couplings. The main motivation for this work comes from the problems of neuroscience where excitatory couplings are proved to be the predominant type of interaction between neurons of the brain. In this paper it is shown that there are two modes depending on the type of coupling between the elements: the mode with a stable heteroclinic cycle and the mode with a stable limit cycle. Our second goal is to examine the chaotic dynamics of the generalized three-dimensional Lotka-Volterra model.

  13. Roux-en-Y gastric bypass augments the feeding responses evoked by gastrin releasing peptides

    Science.gov (United States)

    Washington, Martha C.; Mhalhal, Thaer R.; Berger, Tanisha Johnson-Rouse Jose; Heath, John; Seeley, Randy; Sayegh, Ayman I.

    2016-01-01

    Background Roux-en-Y gastric bypass (RYGB) is the most effective method for the treatment of obesity and metabolic disease Roux-en-Y gastric bypass (RYGB) may reduce body weight by altering the feeding responses evoked by the short term satiety peptides. Materials and Methods Here, we measured meal size (MS, chow), intermeal interval (IMI) length and satiety ratio (SR, IMI/MS; food consumed per a unit of time) by the small and the large forms of gastrin releasing peptide (GRP) in rats, GRP-10 and GRP-29 (0, 0.1, 0.5 nmol/kg) infused in the celiac artery (CA, supplies stomach and upper duodenum) and the cranial mesenteric artery (CMA, supplies small and large intestine) in a RYGB rat model. Results GRP-10 reduced MS, prolonged the IMI and increased the SR only in the RYGB group, whereas GRP-29 evoked these responses by both routes and in both groups. Conclusion The RYGB procedure augments the feeding responses evoked by exogenous GRP, possibly by decreasing total food intake, increasing latency to the first meal, decreasing number of meals or altering the sites of action regulating MS and IMI length by the two peptides. PMID:27884350

  14. SNT-1 functions as the Ca2+ sensor for tonic and evoked neurotransmitter release in C. elegans.

    Science.gov (United States)

    Li, Lei; Liu, Haowen; Wang, Wei; Chandra, Mintu; Collins, Brett M; Hu, Zhitao

    2018-05-14

    Synaptotagmin-1 (Syt1) binds Ca 2+ through its tandem C2 domains (C2A and C2B) and triggers Ca 2+ -dependent neurotransmitter release. Here we show that snt-1 , the homolog of mammalian Syt1, functions as the Ca 2+ sensor for both tonic and evoked neurotransmitter release at the C. elegans neuromuscular junction. Mutations that disrupt Ca 2+ binding in double C2 domains of SNT-1 significantly impaired tonic release, whereas disrupting Ca 2+ binding in a single C2 domain had no effect, indicating that the Ca 2+ binding of the two C2 domains is functionally redundant for tonic release. Stimulus-evoked release was significantly reduced in snt-1 mutants, with prolonged release latency as well as faster rise and decay kinetics. Unlike tonic release, evoked release was triggered by Ca 2+ binding solely to the C2B domain. Moreover, we showed that SNT-1 plays an essential role in the priming process in different subpopulations of synaptic vesicles with tight or loose coupling to Ca 2+ entry. SIGNIFICANCE STATEMENT We showed that SNT-1 in C. elegans regulates evoked neurotransmitter release through Ca 2+ binding to its C2B domain, a similar way to Syt1 in the mouse CNS and the fly NMJ. However, the largely decreased tonic release in snt-1 mutants argues SNT-1 has a clamping function. Indeed, Ca 2+ -binding mutations in the C2 domains in SNT-1 significantly reduced the frequency of the miniature excitatory postsynaptic current (mEPSC), indicating that SNT-1 also acts as a Ca 2+ sensor for tonic release. Therefore, revealing the differential mechanisms between invertebrates and vertebrates will provide significant insights into our understanding how synaptic vesicle fusion is regulated. Copyright © 2018 the authors.

  15. Vasopressin facilitates excitatory transmission in slices of the rat dorso-lateral septum.

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    Van den Hooff, P; Urban, I J

    1990-01-01

    The effect of vasopressin on neurons of the rat dorso-lateral septum (DLS) was studied in brain slices with intracellular microelectrodes. Two out of 13 neurons showed a small depolarization, spontaneous activity, and increased input resistances following a 15 min exposure to 10(-6) to 10(-8) M vasopressin (VP). These membrane effects disappeared completely within 3-5 min after the application. The remaining DLS neurons treated with these vasopressin concentrations showed an increase in glutamate-mediated excitatory postsynaptic potentials (EPSPs), evoked by stimulation of the fimbria fibers. As little as 10(-12) MVP increased these EPSPs markedly in nearly 80% of the cells studied. This increase in most of the cells disappeared within 15 min after the application period, whereas the increase in EPSPs induced by 10(-10) M VP outlasted the peptide application period for more than 30 min. Neither the blockade of GABA-ergic synaptic inhibition nor the pre-treatment of the neurons with d(CH2)5-Tyr(Me)-arginine vasopressin or 2-amino-5-phosphonovaleric acid (2-APV), antagonists for the V1 type of vasopressin receptor and NMDA receptors, respectively, interfered with the EPSPs potentiating effect of the peptide. It is concluded that a type of vasopressin receptor other then the V1 type is involved in the long-lasting potentiation of the primarily non-NMDA receptor mediated transmission in DLS neurons.

  16. Excitatory amino acid transporters as potential drug targets

    DEFF Research Database (Denmark)

    Bunch, Lennart; Erichsen, Mette Navy; Jensen, Anders Asbjørn

    2009-01-01

    BACKGROUND: Excitatory amino acid transporters (EAATs) are transmembrane proteins responsible for the uptake of (S)-glutamate (Glu) from the synaptic cleft, thereby terminating the glutamatergic neurotransmitter signal. Today five subtypes have been identified. Except for EAAT2, their individual...

  17. Deep brain stimulation of the ventral hippocampus restores deficits in processing of auditory evoked potentials in a rodent developmental disruption model of schizophrenia.

    Science.gov (United States)

    Ewing, Samuel G; Grace, Anthony A

    2013-02-01

    Existing antipsychotic drugs are most effective at treating the positive symptoms of schizophrenia but their relative efficacy is low and they are associated with considerable side effects. In this study deep brain stimulation of the ventral hippocampus was performed in a rodent model of schizophrenia (MAM-E17) in an attempt to alleviate one set of neurophysiological alterations observed in this disorder. Bipolar stimulating electrodes were fabricated and implanted, bilaterally, into the ventral hippocampus of rats. High frequency stimulation was delivered bilaterally via a custom-made stimulation device and both spectral analysis (power and coherence) of resting state local field potentials and amplitude of auditory evoked potential components during a standard inhibitory gating paradigm were examined. MAM rats exhibited alterations in specific components of the auditory evoked potential in the infralimbic cortex, the core of the nucleus accumbens, mediodorsal thalamic nucleus, and ventral hippocampus in the left hemisphere only. DBS was effective in reversing these evoked deficits in the infralimbic cortex and the mediodorsal thalamic nucleus of MAM-treated rats to levels similar to those observed in control animals. In contrast stimulation did not alter evoked potentials in control rats. No deficits or stimulation-induced alterations were observed in the prelimbic and orbitofrontal cortices, the shell of the nucleus accumbens or ventral tegmental area. These data indicate a normalization of deficits in generating auditory evoked potentials induced by a developmental disruption by acute high frequency, electrical stimulation of the ventral hippocampus. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. The importance of the excitatory amino acid transporter 3 (EAAT3)

    DEFF Research Database (Denmark)

    E. Bjørn-Yoshimoto, Walden; Underhill, Suzanne M.

    2016-01-01

    Abstract The neuronal excitatory amino acid transporter 3 (EAAT3) is fairly ubiquitously expressed in the brain, though it does not necessarily maintain the same function everywhere. It is important in maintaining low local concentrations of glutamate, where its predominant post-synaptic localiza......Abstract The neuronal excitatory amino acid transporter 3 (EAAT3) is fairly ubiquitously expressed in the brain, though it does not necessarily maintain the same function everywhere. It is important in maintaining low local concentrations of glutamate, where its predominant post...

  19. Enhanced Excitatory Connectivity and Disturbed Sound Processing in the Auditory Brainstem of Fragile X Mice.

    Science.gov (United States)

    Garcia-Pino, Elisabet; Gessele, Nikodemus; Koch, Ursula

    2017-08-02

    Hypersensitivity to sounds is one of the prevalent symptoms in individuals with Fragile X syndrome (FXS). It manifests behaviorally early during development and is often used as a landmark for treatment efficacy. However, the physiological mechanisms and circuit-level alterations underlying this aberrant behavior remain poorly understood. Using the mouse model of FXS ( Fmr1 KO ), we demonstrate that functional maturation of auditory brainstem synapses is impaired in FXS. Fmr1 KO mice showed a greatly enhanced excitatory synaptic input strength in neurons of the lateral superior olive (LSO), a prominent auditory brainstem nucleus, which integrates ipsilateral excitation and contralateral inhibition to compute interaural level differences. Conversely, the glycinergic, inhibitory input properties remained unaffected. The enhanced excitation was the result of an increased number of cochlear nucleus fibers converging onto one LSO neuron, without changing individual synapse properties. Concomitantly, immunolabeling of excitatory ending markers revealed an increase in the immunolabeled area, supporting abnormally elevated excitatory input numbers. Intrinsic firing properties were only slightly enhanced. In line with the disturbed development of LSO circuitry, auditory processing was also affected in adult Fmr1 KO mice as shown with single-unit recordings of LSO neurons. These processing deficits manifested as an increase in firing rate, a broadening of the frequency response area, and a shift in the interaural level difference function of LSO neurons. Our results suggest that this aberrant synaptic development of auditory brainstem circuits might be a major underlying cause of the auditory processing deficits in FXS. SIGNIFICANCE STATEMENT Fragile X Syndrome (FXS) is the most common inheritable form of intellectual impairment, including autism. A core symptom of FXS is extreme sensitivity to loud sounds. This is one reason why individuals with FXS tend to avoid social

  20. Tourette syndrome and excitatory substances: is there a connection?

    Science.gov (United States)

    Zou, Li-Ping; Wang, Ying; Zhang, Li-Ping; Zhao, Jian-Bo; Lu, Jin-Fang; Liu, Qun; Wang, Hang-Yan

    2011-05-01

    The objective of this study is to investigate the relationship between excitatory substances by testing the urine in children with Tourette syndrome (TS). We performed a control study involving 44 patients with TS and 44 normal children by investigating the children's daily eating habits. We used the gas chromatograph-mass spectrometer and liquid chromatograph-mass spectrometer from Agilent. Substances for detection included 197 excitatory substances prohibited by the International Olympic Committee and other substances with similar chemical structures or biological functions for urine samples. Forty-four patients who did not take any drugs in the past 2 weeks enrolled in the study. The positive rate in the experiment group was three cases, while it was negative in the control group. The level of 1-testosterone increased in one extremely severe TS patient who ate large amounts of puffed food and drank an average of 350 ml of cola per day. Cathine and other substances with similar chemical constitution or similar biological effects increased in one severe TS patient who ate bags of instant noodles daily, according to the high score of the Yale Global Tic Severity Scale. An increase in ephedrine type, testosterone, and stimulants may be related to the pathogenesis of TS. Unhealthy food possibly causes TS. The relationship between excitatory substances and TS needs to be explored with the goal of providing more information on diagnosing and treating TS.

  1. Location-dependent excitatory synaptic interactions in pyramidal neuron dendrites.

    Directory of Open Access Journals (Sweden)

    Bardia F Behabadi

    Full Text Available Neocortical pyramidal neurons (PNs receive thousands of excitatory synaptic contacts on their basal dendrites. Some act as classical driver inputs while others are thought to modulate PN responses based on sensory or behavioral context, but the biophysical mechanisms that mediate classical-contextual interactions in these dendrites remain poorly understood. We hypothesized that if two excitatory pathways bias their synaptic projections towards proximal vs. distal ends of the basal branches, the very different local spike thresholds and attenuation factors for inputs near and far from the soma might provide the basis for a classical-contextual functional asymmetry. Supporting this possibility, we found both in compartmental models and electrophysiological recordings in brain slices that the responses of basal dendrites to spatially separated inputs are indeed strongly asymmetric. Distal excitation lowers the local spike threshold for more proximal inputs, while having little effect on peak responses at the soma. In contrast, proximal excitation lowers the threshold, but also substantially increases the gain of distally-driven responses. Our findings support the view that PN basal dendrites possess significant analog computing capabilities, and suggest that the diverse forms of nonlinear response modulation seen in the neocortex, including uni-modal, cross-modal, and attentional effects, could depend in part on pathway-specific biases in the spatial distribution of excitatory synaptic contacts onto PN basal dendritic arbors.

  2. Adverse Weather Evokes Nostalgia.

    Science.gov (United States)

    van Tilburg, Wijnand A P; Sedikides, Constantine; Wildschut, Tim

    2018-03-01

    Four studies examined the link between adverse weather and the palliative role of nostalgia. We proposed and tested that (a) adverse weather evokes nostalgia (Hypothesis 1); (b) adverse weather causes distress, which predicts elevated nostalgia (Hypothesis 2); (c) preventing nostalgia exacerbates weather-induced distress (Hypothesis 3); and (d) weather-evoked nostalgia confers psychological benefits (Hypothesis 4). In Study 1, participants listened to recordings of wind, thunder, rain, and neutral sounds. Adverse weather evoked nostalgia. In Study 2, participants kept a 10-day diary recording weather conditions, distress, and nostalgia. We also obtained meteorological data. Adverse weather perceptions were positively correlated with distress, which predicted higher nostalgia. Also, adverse natural weather was associated with corresponding weather perceptions, which predicted elevated nostalgia. (Results were mixed for rain.) In Study 3, preventing nostalgia (via cognitive load) increased weather-evoked distress. In Study 4, weather-evoked nostalgia was positively associated with psychological benefits. The findings pioneer the relevance of nostalgia as source of comfort in adverse weather.

  3. Genetic controls balancing excitatory and inhibitory synaptogenesis in neurodevelopmental disorder models

    Directory of Open Access Journals (Sweden)

    Cheryl L Gatto

    2010-06-01

    Full Text Available Proper brain function requires stringent balance of excitatory and inhibitory synapse formation during neural circuit assembly. Mutation of genes that normally sculpt and maintain this balance results in severe dysfunction, causing neurodevelopmental disorders including autism, epilepsy and Rett syndrome. Such mutations may result in defective architectural structuring of synaptic connections, molecular assembly of synapses and/or functional synaptogenesis. The affected genes often encode synaptic components directly, but also include regulators that secondarily mediate the synthesis or assembly of synaptic proteins. The prime example is Fragile X syndrome (FXS, the leading heritable cause of both intellectual disability and autism spectrum disorders. FXS results from loss of mRNA-binding FMRP, which regulates synaptic transcript trafficking, stability and translation in activity-dependent synaptogenesis and plasticity mechanisms. Genetic models of FXS exhibit striking excitatory and inhibitory synapse imbalance, associated with impaired cognitive and social interaction behaviors. Downstream of translation control, a number of specific synaptic proteins regulate excitatory versus inhibitory synaptogenesis, independently or combinatorially, and loss of these proteins is also linked to disrupted neurodevelopment. The current effort is to define the cascade of events linking transcription, translation and the role of specific synaptic proteins in the maintenance of excitatory versus inhibitory synapses during neural circuit formation. This focus includes mechanisms that fine-tune excitation and inhibition during the refinement of functional synaptic circuits, and later modulate this balance throughout life. The use of powerful new genetic models has begun to shed light on the mechanistic bases of excitation/inhibition imbalance for a range of neurodevelopmental disease states.

  4. Intramuscular temperature modulates glutamate-evoked masseter muscle pain intensity in humans.

    Science.gov (United States)

    Sato, Hitoshi; Castrillon, Eduardo E; Cairns, Brian E; Bendixen, Karina H; Wang, Kelun; Nakagawa, Taneaki; Wajima, Koichi; Svensson, Peter

    2015-01-01

    To determine whether glutamate-evoked jaw muscle pain is altered by the temperature of the solution injected. Sixteen healthy volunteers participated and received injections of hot (48°C), neutral (36°C), or cold (3°C) solutions (0.5 mL) of glutamate or isotonic saline into the masseter muscle. Pain intensity was assessed with an electronic visual analog scale (eVAS). Numeric rating scale (NRS) scores of unpleasantness and temperature perception, pain-drawing areas, and pressure pain thresholds (PPTs) were also measured. Participants filled out the McGill Pain Questionnaire (MPQ). Two-way or three-way repeated measures ANOVA were used for data analyses. Injection of hot glutamate and cold glutamate solutions significantly increased and decreased, respectively, the peak pain intensity compared with injection of neutral glutamate solution. The duration of glutamate-evoked pain was significantly longer when hot glutamate was injected than when cold glutamate was injected. No significant effect of temperature on pain intensity was observed when isotonic saline was injected. No effect of solution temperature was detected on unpleasantness, heat perception, cold perception, area of pain drawings, or PPTs. There was a significantly greater use of the "numb" term in the MPQ to describe the injection of cold solutions compared to the injection of both neutral and hot solutions. Glutamate-evoked jaw muscle pain was significantly altered by the temperature of the injection solution. Although temperature perception in the jaw muscle is poor, pain intensity is increased when the muscle tissue temperature is elevated.

  5. Inhibition of synaptically evoked cortical acetylcholine release by adenosine: an in vivo microdialysis study in the rat.

    Science.gov (United States)

    Materi, L M; Rasmusson, D D; Semba, K

    2000-01-01

    The release of cortical acetylcholine from the intracortical axonal terminals of cholinergic basal forebrain neurons is closely associated with electroencephalographic activity. One factor which may act to reduce cortical acetylcholine release and promote sleep is adenosine. Using in vivo microdialysis, we examined the effect of adenosine and selective adenosine receptor agonists and antagonists on cortical acetylcholine release evoked by electrical stimulation of the pedunculopontine tegmental nucleus in urethane anesthetized rats. All drugs were administered locally within the cortex by reverse dialysis. None of the drugs tested altered basal release of acetylcholine in the cortex. Adenosine significantly reduced evoked cortical acetylcholine efflux in a concentration-dependent manner. This was mimicked by the adenosine A(1) receptor selective agonist N(6)-cyclopentyladenosine and blocked by the selective A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). The A(2A) receptor agonist 2-[p-(2-carboxyethyl)-phenethylamino]-5'-N-ethylcarboxamidoadenosi ne hydrochloride (CGS 21680) did not alter evoked cortical acetylcholine release even in the presence of DPCPX. Administered alone, neither DPCPX nor the non-selective adenosine receptor antagonist caffeine affected evoked cortical acetylcholine efflux. Simultaneous delivery of the adenosine uptake inhibitors dipyridamole and S-(4-nitrobenzyl)-6-thioinosine significantly reduced evoked cortical acetylcholine release, and this effect was blocked by the simultaneous administration of caffeine. These data indicate that activation of the A(1) adenosine receptor inhibits acetylcholine release in the cortex in vivo while the A(2A) receptor does not influence acetylcholine efflux. Such inhibition of cortical acetylcholine release by adenosine may contribute to an increased propensity to sleep during prolonged wakefulness.

  6. Miniature excitatory synaptic currents in cultured hippocampal neurons.

    Science.gov (United States)

    Finch, D M; Fisher, R S; Jackson, M B

    1990-06-04

    We performed patch clamp recordings in the whole cell mode from cultured embryonic mouse hippocampal neurons. In bathing solutions containing tetrodotoxin (TTX), the cells showed spontaneous inward currents (SICs) ranging in size from 1 to 100 pA. Several observations indicated that the SICs were miniature excitatory synaptic currents mediated primarily by non-NMDA (N-methyl-D-aspartate) excitatory amino acid receptors: the rising phase of SICs was fast (1 ms to half amplitude at room temperature) and smooth, suggesting unitary events. The SICs were blocked by the broad-spectrum glutamate receptor antagonist gamma-D-glutamylglycine (DGG), but not by the selective NMDA-receptor antagonist D-2-amino-5-phosphonovaleric acid (5-APV). SICs were also blocked by desensitizing concentrations of quisqualate. Incubating cells in tetanus toxin, which blocks exocytotic transmitter release, eliminated SICs. The presence of SICs was consistent with the morphological arrangement of glutamatergic innervation in the cell cultures demonstrated immunohistochemically. Spontaneous outward currents (SOCs) were blocked by bicuculline and presumed to be mediated by GABAA receptors. This is consistent with immunohistochemical demonstration of GABAergic synapses. SIC frequency was increased in a calcium dependent manner by bathing the cells in a solution high in K+, and application of the dihydropyridine L-type calcium channel agonist BAY K 8644 increased the frequency of SICs. Increases in SIC frequency produced by high K+ solutions were reversed by Cd2+ and omega-conotoxin GVIA, but not by the selective L-type channel antagonist nimodipine. This suggested that presynaptic L-type channels were in a gating mode that was not blocked by nimodipine, and/or that another class of calcium channel makes a dominant contribution to excitatory transmitter release.

  7. Music evokes vivid autobiographical memories.

    Science.gov (United States)

    Belfi, Amy M; Karlan, Brett; Tranel, Daniel

    2016-08-01

    Music is strongly intertwined with memories-for example, hearing a song from the past can transport you back in time, triggering the sights, sounds, and feelings of a specific event. This association between music and vivid autobiographical memory is intuitively apparent, but the idea that music is intimately tied with memories, seemingly more so than other potent memory cues (e.g., familiar faces), has not been empirically tested. Here, we compared memories evoked by music to those evoked by famous faces, predicting that music-evoked autobiographical memories (MEAMs) would be more vivid. Participants listened to 30 songs, viewed 30 faces, and reported on memories that were evoked. Memories were transcribed and coded for vividness as in Levine, B., Svoboda, E., Hay, J. F., Winocur, G., & Moscovitch, M. [2002. Aging and autobiographical memory: Dissociating episodic from semantic retrieval. Psychology and Aging, 17, 677-689]. In support of our hypothesis, MEAMs were more vivid than autobiographical memories evoked by faces. MEAMs contained a greater proportion of internal details and a greater number of perceptual details, while face-evoked memories contained a greater number of external details. Additionally, we identified sex differences in memory vividness: for both stimulus categories, women retrieved more vivid memories than men. The results show that music not only effectively evokes autobiographical memories, but that these memories are more vivid than those evoked by famous faces.

  8. SURAMIN AS AN INHIBITOR OF SYMPATHETIC EXCITATORY. JUNCTION POTENTIALS: STUDY IN GUINEA PIG ISOLATED VAS DEFERENS

    Directory of Open Access Journals (Sweden)

    M AYATOLLAHI

    2001-06-01

    Full Text Available

    Introduction. Suramin, as a selective P2x-Pourinoceptor antagonist can inhibit the sympathetic excitatory junction potentials (SEJPs. Experiments have shown that the biphasic contractile responses (bcr in smooth muscles of vascular and vas deferens (vds is evoked by cotransmission of ATP and neuradrenaline. Therefore, vds is considered as a model for studying the role of A TP and antagonizing its effect. By using different concentrations of Suramin, its antagonistic effect in phase one of bcr is observed To confirm the purinergic origin of SEJPs, some experiments should be performed electrophysiologically at different concentrations of Suramin.
    Methods. Suramin was dissolved in distilled water and after diluting with physiological salt solution freezed as a stock solution at concentration of 10-1M. After killing and dissecting the albino male guinea pigs (weighing 2S0-300 gm, both testes were pushed up to give out the whole vds. The vds was cleaned from surrounding tissues and cut from epididymic and prostatic ends. vds was maintained at 3SC in physiological salt solution bubbled with 9S percent O2 and 5 percent CO2. Intracellular microelectrodes (with resistance of 20-40 MQ recordings were made from prostatic end of vds.
    Results. The resting membrane potential of the control smooth muscle cells was 67.4±.0.7 mV (n=48. Electrical stimulation at frequency of 0.5 Hz evokes SEJPs which are magnified consistently due to facilitation. Mean magnitude of fully facilitated SEJPs which were evoked from control cells was 8.5±0.8 mV (n=23. Further facilitation was evoked at frequencies of 1 Hz or 2 Hz, because SEJPs were obtained at the threshold limit to begin the action potentials which were 55 mV in most cells. It was difficult to estimate correctly the threshold potential in a cell because disseminated potential might

  9. Spinal Hb9::Cre-derived excitatory interneurons contribute to rhythm generation in the mouse.

    Science.gov (United States)

    Caldeira, Vanessa; Dougherty, Kimberly J; Borgius, Lotta; Kiehn, Ole

    2017-01-27

    Rhythm generating neurons are thought to be ipsilaterally-projecting excitatory neurons in the thoracolumbar mammalian spinal cord. Recently, a subset of Shox2 interneurons (Shox2 non-V2a INs) was found to fulfill these criteria and make up a fraction of the rhythm-generating population. Here we use Hb9::Cre mice to genetically manipulate Hb9::Cre-derived excitatory interneurons (INs) in order to determine the role of these INs in rhythm generation. We demonstrate that this line captures a consistent population of spinal INs which is mixed with respect to neurotransmitter phenotype and progenitor domain, but does not overlap with the Shox2 non-V2a population. We also show that Hb9::Cre-derived INs include the comparatively small medial population of INs which continues to express Hb9 postnatally. When excitatory neurotransmission is selectively blocked by deleting Vglut2 from Hb9::Cre-derived INs, there is no difference in left-right and/or flexor-extensor phasing between these cords and controls, suggesting that excitatory Hb9::Cre-derived INs do not affect pattern generation. In contrast, the frequencies of locomotor activity are significantly lower in cords from Hb9::Cre-Vglut2 Δ/Δ mice than in cords from controls. Collectively, our findings indicate that excitatory Hb9::Cre-derived INs constitute a distinct population of neurons that participates in the rhythm generating kernel for spinal locomotion.

  10. Npas4 regulates excitatory-inhibitory balance within neural circuits through cell-type-specific gene programs.

    Science.gov (United States)

    Spiegel, Ivo; Mardinly, Alan R; Gabel, Harrison W; Bazinet, Jeremy E; Couch, Cameron H; Tzeng, Christopher P; Harmin, David A; Greenberg, Michael E

    2014-05-22

    The nervous system adapts to experience by inducing a transcriptional program that controls important aspects of synaptic plasticity. Although the molecular mechanisms of experience-dependent plasticity are well characterized in excitatory neurons, the mechanisms that regulate this process in inhibitory neurons are only poorly understood. Here, we describe a transcriptional program that is induced by neuronal activity in inhibitory neurons. We find that, while neuronal activity induces expression of early-response transcription factors such as Npas4 in both excitatory and inhibitory neurons, Npas4 activates distinct programs of late-response genes in inhibitory and excitatory neurons. These late-response genes differentially regulate synaptic input to these two types of neurons, promoting inhibition onto excitatory neurons while inducing excitation onto inhibitory neurons. These findings suggest that the functional outcomes of activity-induced transcriptional responses are adapted in a cell-type-specific manner to achieve a circuit-wide homeostatic response. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Excitatory transmission from the amygdala to nucleus accumbens facilitates reward seeking.

    Science.gov (United States)

    Stuber, Garret D; Sparta, Dennis R; Stamatakis, Alice M; van Leeuwen, Wieke A; Hardjoprajitno, Juanita E; Cho, Saemi; Tye, Kay M; Kempadoo, Kimberly A; Zhang, Feng; Deisseroth, Karl; Bonci, Antonello

    2011-06-29

    The basolateral amygdala (BLA) has a crucial role in emotional learning irrespective of valence. The BLA projection to the nucleus accumbens (NAc) is thought to modulate cue-triggered motivated behaviours, but our understanding of the interaction between these two brain regions has been limited by the inability to manipulate neural-circuit elements of this pathway selectively during behaviour. To circumvent this limitation, we used in vivo optogenetic stimulation or inhibition of glutamatergic fibres from the BLA to the NAc, coupled with intracranial pharmacology and ex vivo electrophysiology. Here we show that optical stimulation of the pathway from the BLA to the NAc in mice reinforces behavioural responding to earn additional optical stimulation of these synaptic inputs. Optical stimulation of these glutamatergic fibres required intra-NAc dopamine D1-type receptor signalling, but not D2-type receptor signalling. Brief optical inhibition of fibres from the BLA to the NAc reduced cue-evoked intake of sucrose, demonstrating an important role of this specific pathway in controlling naturally occurring reward-related behaviour. Moreover, although optical stimulation of glutamatergic fibres from the medial prefrontal cortex to the NAc also elicited reliable excitatory synaptic responses, optical self-stimulation behaviour was not observed by activation of this pathway. These data indicate that whereas the BLA is important for processing both positive and negative affect, the glutamatergic pathway from the BLA to the NAc, in conjunction with dopamine signalling in the NAc, promotes motivated behavioural responding. Thus, optogenetic manipulation of anatomically distinct synaptic inputs to the NAc reveals functionally distinct properties of these inputs in controlling reward-seeking behaviours.

  12. Inhibition of excitatory synaptic transmission in the trigeminal motor nucleus by the nitric oxide-cyclic GMP signaling pathway.

    Science.gov (United States)

    Pose, Inés; Silveira, Valentina; Morales, Francisco R

    2011-06-01

    Nitric oxide (NO) and cyclic GMP (cGMP) suppressed glutamatergic synaptic transmission to trigeminal motoneurons in brain stem slices of neonatal rats. Histological studies showed guanylate cyclase (GC) containing fibers in the trigeminal motor pool. Glutamatergic excitatory postsynaptic currents (EPSCs) were recorded from neonatal trigeminal motoneurons in response to stimulation of the supratrigeminal nucleus (SuV). The NO donors DETA/NONOate (DETA/NO), at a concentration which released 275.1 nM of NO, and Spermine/NONOate (Sper/NO) reduced the amplitude of the EPSC to 52.7±0.6% and 60.1±10.8% of control values, respectively. These actions were not blocked by the GC inhibitors, ODQ or NS-2028. However, in the presence of YC-1 or BAY41-2272, modulators of GC that act as NO sensitizers, lower and otherwise ineffective concentrations of DETA/NO induced a reduction of the EPSC to 60.6±5.2%. Moreover, NO effects were mimicked by 8BrcGMP and by Zaprinast, an inhibitor of Phosphodiesterase 5. Glutamatergic currents evoked by exogenous glutamate were not reduced by DETA/NO nor 8BrcGMP. Paired-pulse facilitation was increased by NO donors. Under "minimal stimulation" conditions NO donors and cGMP increased the failure rate of evoked EPSCs. Protein kinase inhibitors antagonized cGMP effects. The results suggest that NO, through the synthesis of cGMP, presynaptically inhibits glutamatergic synaptic transmission on trigeminal motoneurons. We propose that NO has complex actions on motor pools; specific studies are needed to elucidate their physiological significance in the behaving animal. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Hyperactivity of newborn Pten knock-out neurons results from increased excitatory synaptic drive.

    Science.gov (United States)

    Williams, Michael R; DeSpenza, Tyrone; Li, Meijie; Gulledge, Allan T; Luikart, Bryan W

    2015-01-21

    Developing neurons must regulate morphology, intrinsic excitability, and synaptogenesis to form neural circuits. When these processes go awry, disorders, including autism spectrum disorder (ASD) or epilepsy, may result. The phosphatase Pten is mutated in some patients having ASD and seizures, suggesting that its mutation disrupts neurological function in part through increasing neuronal activity. Supporting this idea, neuronal knock-out of Pten in mice can cause macrocephaly, behavioral changes similar to ASD, and seizures. However, the mechanisms through which excitability is enhanced following Pten depletion are unclear. Previous studies have separately shown that Pten-depleted neurons can drive seizures, receive elevated excitatory synaptic input, and have abnormal dendrites. We therefore tested the hypothesis that developing Pten-depleted neurons are hyperactive due to increased excitatory synaptogenesis using electrophysiology, calcium imaging, morphological analyses, and modeling. This was accomplished by coinjecting retroviruses to either "birthdate" or birthdate and knock-out Pten in granule neurons of the murine neonatal dentate gyrus. We found that Pten knock-out neurons, despite a rapid onset of hypertrophy, were more active in vivo. Pten knock-out neurons fired at more hyperpolarized membrane potentials, displayed greater peak spike rates, and were more sensitive to depolarizing synaptic input. The increased sensitivity of Pten knock-out neurons was due, in part, to a higher density of synapses located more proximal to the soma. We determined that increased synaptic drive was sufficient to drive hypertrophic Pten knock-out neurons beyond their altered action potential threshold. Thus, our work contributes a developmental mechanism for the increased activity of Pten-depleted neurons. Copyright © 2015 the authors 0270-6474/15/350943-17$15.00/0.

  14. Schaffer collateral inputs to CA1 excitatory and inhibitory neurons follow different connectivity rules.

    Science.gov (United States)

    Kwon, Osung; Feng, Linqing; Druckmann, Shaul; Kim, Jinhyun

    2018-05-04

    Neural circuits, governed by a complex interplay between excitatory and inhibitory neurons, are the substrate for information processing, and the organization of synaptic connectivity in neural network is an important determinant of circuit function. Here, we analyzed the fine structure of connectivity in hippocampal CA1 excitatory and inhibitory neurons innervated by Schaffer collaterals (SCs) using mGRASP in male mice. Our previous study revealed spatially structured synaptic connectivity between CA3-CA1 pyramidal cells (PCs). Surprisingly, parvalbumin-positive interneurons (PVs) showed a significantly more random pattern spatial structure. Notably, application of Peters' Rule for synapse prediction by random overlap between axons and dendrites enhanced structured connectivity in PCs, but, by contrast, made the connectivity pattern in PVs more random. In addition, PCs in a deep sublayer of striatum pyramidale appeared more highly structured than PCs in superficial layers, and little or no sublayer specificity was found in PVs. Our results show that CA1 excitatory PCs and inhibitory PVs innervated by the same SC inputs follow different connectivity rules. The different organizations of fine scale structured connectivity in hippocampal excitatory and inhibitory neurons provide important insights into the development and functions of neural networks. SIGNIFICANCE STATEMENT Understanding how neural circuits generate behavior is one of the central goals of neuroscience. An important component of this endeavor is the mapping of fine-scale connection patterns that underlie, and help us infer, signal processing in the brain. Here, using our recently developed synapse detection technology (mGRASP and neuTube), we provide detailed profiles of synaptic connectivity in excitatory (CA1 pyramidal) and inhibitory (CA1 parvalbumin-positive) neurons innervated by the same presynaptic inputs (CA3 Schaffer collaterals). Our results reveal that these two types of CA1 neurons follow

  15. Spinal Hb9::Cre-derived excitatory interneurons contribute to rhythm generation in the mouse

    DEFF Research Database (Denmark)

    Caldeira, Vanessa; Dougherty, Kimberly J.; Borgius, Lotta

    2017-01-01

    Rhythm generating neurons are thought to be ipsilaterally-projecting excitatory neurons in the thoracolumbar mammalian spinal cord. Recently, a subset of Shox2 interneurons (Shox2 non-V2a INs) was found to fulfill these criteria and make up a fraction of the rhythm-generating population. Here we...... than in cords from controls. Collectively, our findings indicate that excitatory Hb9::Cre-derived INs constitute a distinct population of neurons that participates in the rhythm generating kernel for spinal locomotion....... use Hb9::Cre mice to genetically manipulate Hb9::Cre-derived excitatory interneurons (INs) in order to determine the role of these INs in rhythm generation. We demonstrate that this line captures a consistent population of spinal INs which is mixed with respect to neurotransmitter phenotype...

  16. Proprioceptive evoked gamma oscillations

    DEFF Research Database (Denmark)

    Arnfred, S.M.; Hansen, Lars Kai; Parnas, J.

    2007-01-01

    A proprioceptive stimulus consisting of a weight change of a handheld load has recently been shown to elicit an evoked potential. Previously, somatosensory gamma oscillations have only been evoked by electrical stimuli. We conjectured that a natural proprioceptive stimulus also would be able...... to evoke gamma oscillations. EEG was recorded using 64 channels in 14 healthy subjects. In each of three runs a stimulus of 100 g load increment in each hand was presented in 120 trials. Data were wavelet transformed and runs collapsed. Inter-trial phase coherence (ITPC) was computed as the best measure...

  17. Fast voltage-sensitive dye imaging of excitatory and inhibitory synaptic transmission in the rat granular retrosplenial cortex.

    Science.gov (United States)

    Nixima, Ken'ichi; Okanoya, Kazuo; Ichinohe, Noritaka; Kurotani, Tohru

    2017-09-01

    Rodent granular retrosplenial cortex (GRS) has dense connections between the anterior thalamic nuclei (ATN) and hippocampal formation. GRS superficial pyramidal neurons exhibit distinctive late spiking (LS) firing property and form patchy clusters with prominent apical dendritic bundles. The aim of this study was to investigate spatiotemporal dynamics of signal transduction in the GRS induced by ATN afferent stimulation by using fast voltage-sensitive dye imaging in rat brain slices. In coronal slices, layer 1a stimulation, which presumably activated thalamic fibers, evoked propagation of excitatory synaptic signals from layers 2-4 to layers 5-6 in a direction perpendicular to the layer axis, followed by transverse signal propagation within each layer. In the presence of ionotropic glutamate receptor antagonists, inhibitory responses were observed in superficial layers, induced by direct activation of inhibitory interneurons in layer 1. In horizontal slices, excitatory signals in deep layers propagated transversely mainly from posterior to anterior via superficial layers. Cortical inhibitory responses upon layer 1a stimulation in horizontal slices were weaker than those in the coronal slices. Observed differences between coronal and horizontal planes suggest anisotropy of the intracortical circuitry. In conclusion, ATN inputs are processed differently in coronal and horizontal planes of the GRS and then conveyed to other cortical areas. In both planes, GRS superficial layers play an important role in signal propagation, which suggests that superficial neuronal cascade is crucial in the integration of multiple information sources. NEW & NOTEWORTHY Superficial neurons in the rat granular retrosplenial cortex (GRS) show distinctive late-spiking (LS) firing property. However, little is known about spatiotemporal dynamics of signal transduction in the GRS. We demonstrated LS neuron network relaying thalamic inputs to deep layers and anisotropic distribution of

  18. Noise-evoked otoacoustic emissions in humans

    NARCIS (Netherlands)

    Maat, B; Wit, HP; van Dijk, P

    2000-01-01

    Click-evoked otoacoustic emissions (CEOAEs) and acoustical responses evoked by bandlimited Gaussian noise (noise-evoked otoacoustic emissions; NEOAEs) were measured in three normal-hearing subjects. For the NEOAEs the first- and second-order Wiener kernel and polynomial correlation functions up to

  19. Excitatory and inhibitory synaptic mechanisms at the first stage of integration in the electroreception system of the shark

    DEFF Research Database (Denmark)

    Rotem, Naama; Sestieri, Emanuel; Hounsgaard, Jørn Dybkjær

    2014-01-01

    High impulse rate in afferent nerves is a common feature in many sensory systems that serve to accommodate a wide dynamic range. However, the first stage of integration should be endowed with specific properties that enable efficient handling of the incoming information. In elasmobranches...... of this afferent pathway. We found that stimulating the afferent nerve activates a mixture of excitatory and inhibitory synapses mediated by AMPA-like and GABAA receptors, respectively. The excitatory synapses that are extremely efficient in activating the postsynaptic neurons display unusual voltage dependence......, enabling them to operate as a current source. The inhibitory input is powerful enough to completely eliminate the excitatory action of the afferent nerve but is ineffective regarding other excitatory inputs. These observations can be explained by the location and efficiency of the synapses. We conclude...

  20. Bistability Analysis of Excitatory-Inhibitory Neural Networks in Limited-Sustained-Activity Regime

    International Nuclear Information System (INIS)

    Ni Yun; Wu Liang; Wu Dan; Zhu Shiqun

    2011-01-01

    Bistable behavior of neuronal complex networks is investigated in the limited-sustained-activity regime when the network is composed of excitatory and inhibitory neurons. The standard stability analysis is performed on the two metastable states separately. Both theoretical analysis and numerical simulations show consistently that the difference between time scales of excitatory and inhibitory populations can influence the dynamical behaviors of the neuronal networks dramatically, leading to the transition from bistable behaviors with memory effects to the collapse of bistable behaviors. These results may suggest one possible neuronal information processing by only tuning time scales. (interdisciplinary physics and related areas of science and technology)

  1. Expression of gastrin-releasing peptide by excitatory interneurons in the mouse superficial dorsal horn.

    Science.gov (United States)

    Gutierrez-Mecinas, Maria; Watanabe, Masahiko; Todd, Andrew J

    2014-12-11

    Gastrin-releasing peptide (GRP) and its receptor have been shown to play an important role in the sensation of itch. However, although GRP immunoreactivity has been detected in the spinal dorsal horn, there is debate about whether this originates from primary afferents or local excitatory interneurons. We therefore examined the relation of GRP immunoreactivity to that seen with antibodies that label primary afferent or excitatory interneuron terminals. We tested the specificity of the GRP antibody by preincubating with peptides with which it could potentially cross-react. We also examined tissue from a mouse line in which enhanced green fluorescent protein (EGFP) is expressed under control of the GRP promoter. GRP immunoreactivity was seen in both primary afferent and non-primary glutamatergic axon terminals in the superficial dorsal horn. However, immunostaining was blocked by pre-incubation of the antibody with substance P, which is present at high levels in many nociceptive primary afferents. EGFP+ cells in the GRP-EGFP mouse did not express Pax2, and their axons contained the vesicular glutamate transporter 2 (VGLUT2), indicating that they are excitatory interneurons. In most cases, their axons were also GRP-immunoreactive. Multiple-labelling immunocytochemical studies indicated that these cells did not express either of the preprotachykinin peptides, and that they generally lacked protein kinase Cγ, which is expressed by a subset of the excitatory interneurons in this region. These results show that GRP is expressed by a distinct population of excitatory interneurons in laminae I-II that are likely to be involved in the itch pathway. They also suggest that the GRP immunoreactivity seen in primary afferents in previous studies may have resulted from cross-reaction of the GRP antibody with substance P or the closely related peptide neurokinin A.

  2. CDKL5 knockout leads to altered inhibitory transmission in the cerebellum of adult mice.

    Science.gov (United States)

    Sivilia, S; Mangano, C; Beggiato, S; Giuliani, A; Torricella, R; Baldassarro, V A; Fernandez, M; Lorenzini, L; Giardino, L; Borelli, A C; Ferraro, L; Calzà, L

    2016-06-01

    Mutations in the X-linked cyclin-dependent kinase-like 5 gene (CDKL5) are associated to severe neurodevelopmental alterations including motor symptoms. In order to elucidate the neurobiological substrate of motor symptoms in CDKL5 syndrome, we investigated the motor function, GABA and glutamate pathways in the cerebellum of CDKL5 knockout female mice. Behavioural data indicate that CDKL5-KO mice displayed impaired motor coordination on the Rotarod test, and altered steps, as measured by the gait analysis using the CatWalk test. A higher reduction in spontaneous GABA efflux, than that in glutamate, was observed in CDKL5-KO mouse cerebellar synaptosomes, leading to a significant increase of spontaneous glutamate/GABA efflux ratio in these animals. On the contrary, there were no differences between groups in K(+) -evoked GABA and glutamate efflux. The anatomical analysis of cerebellar excitatory and inhibitory pathways showed a selective defect of the GABA-related marker GAD67 in the molecular layer in CDKL5-KO mice, while the glutamatergic marker VGLUT1 was unchanged in the same area. Fine cerebellar structural abnormalities such as a reduction of the inhibitory basket 'net' estimated volume and an increase of the pinceau estimated volume were also observed in CDKL5-KO mice. Finally, the BDNF mRNA expression level in the cerebellum, but not in the hippocampus, was reduced compared with WT animals. These data suggest that CDKL5 deletion during development more markedly impairs the establishment of a correct GABAergic cerebellar network than that of glutamatergic one, leading to the behavioural symptoms associated with CDKL5 mutation. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  3. Thermal grill-evoked sensations of heat correlate with cold pain threshold and are enhanced by menthol and cinnamaldehyde.

    Science.gov (United States)

    Averbeck, B; Rucker, F; Laubender, R P; Carr, R W

    2013-05-01

    Thunberg's thermal grill produces a sensation of strong heat upon skin contact with spatially interlaced innocuous warm and cool stimuli. To examine the classes of peripheral axons that might contribute to this illusion, the effects of topical l-menthol, an activator of TRPM8, and cinnamaldehyde, a TRPA1 agonist, on the magnitude of thermal sensations were examined during grill stimulation in healthy volunteers. Under control conditions, cutaneous grill stimulation (interlaced 20/40 °C) evoked a sensation of heat, and for individual subjects, the magnitude of this heat sensation was positively correlated with cold pain threshold (CPT). Menthol increased the CPT and enhanced the magnitude of grill-evoked heat. Cinnamaldehyde intensified warm sensations, reduced heat pain threshold and also enhanced grill-evoked heat. Both TRPM8-expressing and TRPA1-expressing afferent axons can affect grill-evoked thermal sensations. The enhancement of grill-evoked sensations of temperature with menthol and cinnamaldehyde may provide an additional clinically relevant means of testing altered thermal sensitivity, which is often affected in neuropathic patient groups. © 2012 European Federation of International Association for the Study of Pain Chapters.

  4. Deconvolution of the vestibular evoked myogenic potential.

    Science.gov (United States)

    Lütkenhöner, Bernd; Basel, Türker

    2012-02-07

    The vestibular evoked myogenic potential (VEMP) and the associated variance modulation can be understood by a convolution model. Two functions of time are incorporated into the model: the motor unit action potential (MUAP) of an average motor unit, and the temporal modulation of the MUAP rate of all contributing motor units, briefly called rate modulation. The latter is the function of interest, whereas the MUAP acts as a filter that distorts the information contained in the measured data. Here, it is shown how to recover the rate modulation by undoing the filtering using a deconvolution approach. The key aspects of our deconvolution algorithm are as follows: (1) the rate modulation is described in terms of just a few parameters; (2) the MUAP is calculated by Wiener deconvolution of the VEMP with the rate modulation; (3) the model parameters are optimized using a figure-of-merit function where the most important term quantifies the difference between measured and model-predicted variance modulation. The effectiveness of the algorithm is demonstrated with simulated data. An analysis of real data confirms the view that there are basically two components, which roughly correspond to the waves p13-n23 and n34-p44 of the VEMP. The rate modulation corresponding to the first, inhibitory component is much stronger than that corresponding to the second, excitatory component. But the latter is more extended so that the two modulations have almost the same equivalent rectangular duration. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Loss of MeCP2 From Forebrain Excitatory Neurons Leads to Cortical Hyperexcitation and Seizures

    Science.gov (United States)

    Zhang, Wen; Peterson, Matthew; Beyer, Barbara; Frankel, Wayne N.

    2014-01-01

    Mutations of MECP2 cause Rett syndrome (RTT), a neurodevelopmental disorder leading to loss of motor and cognitive functions, impaired social interactions, and seizure at young ages. Defects of neuronal circuit development and function are thought to be responsible for the symptoms of RTT. The majority of RTT patients show recurrent seizures, indicating that neuronal hyperexcitation is a common feature of RTT. However, mechanisms underlying hyperexcitation in RTT are poorly understood. Here we show that deletion of Mecp2 from cortical excitatory neurons but not forebrain inhibitory neurons in the mouse leads to spontaneous seizures. Selective deletion of Mecp2 from excitatory but not inhibitory neurons in the forebrain reduces GABAergic transmission in layer 5 pyramidal neurons in the prefrontal and somatosensory cortices. Loss of MeCP2 from cortical excitatory neurons reduces the number of GABAergic synapses in the cortex, and enhances the excitability of layer 5 pyramidal neurons. Using single-cell deletion of Mecp2 in layer 2/3 pyramidal neurons, we show that GABAergic transmission is reduced in neurons without MeCP2, but is normal in neighboring neurons with MeCP2. Together, these results suggest that MeCP2 in cortical excitatory neurons plays a critical role in the regulation of GABAergic transmission and cortical excitability. PMID:24523563

  6. Contact Heat Evoked Potentials (CHEPs) in Patients with Mild-Moderate Alzheimer's Disease and Matched Control-A Pilot Study

    DEFF Research Database (Denmark)

    Jensen-Dahm, Christina; Madsen, Caspar Skau; Waldemar, Gunhild

    2016-01-01

    OBJECTIVE: Clinical studies have found that patients with Alzheimer's disease report pain of less intensity and with a lower affective response, which has been thought to be due to altered pain processing. The authors wished to examine the cerebral processing of non-painful and painful stimuli...... threshold and heat pain threshold. Somatosensory evoked potentials, amplitude, and latency were within normal range and similar for the two groups. CONCLUSIONS: The findings suggest that the processing of non-painful and painful stimuli is preserved in patients with mild to moderate Alzheimer's disease....... using somatosensory evoked potentials and contact heat evoked potentials in patients with Alzheimer's disease and in healthy elderly controls. DESIGN: Case-control study SETTING AND SUBJECTS: Twenty outpatients with mild-moderate Alzheimer's disease and in 17 age- and gender-matched healthy controls...

  7. Evoked emotions predict food choice.

    Science.gov (United States)

    Dalenberg, Jelle R; Gutjar, Swetlana; Ter Horst, Gert J; de Graaf, Kees; Renken, Remco J; Jager, Gerry

    2014-01-01

    In the current study we show that non-verbal food-evoked emotion scores significantly improve food choice prediction over merely liking scores. Previous research has shown that liking measures correlate with choice. However, liking is no strong predictor for food choice in real life environments. Therefore, the focus within recent studies shifted towards using emotion-profiling methods that successfully can discriminate between products that are equally liked. However, it is unclear how well scores from emotion-profiling methods predict actual food choice and/or consumption. To test this, we proposed to decompose emotion scores into valence and arousal scores using Principal Component Analysis (PCA) and apply Multinomial Logit Models (MLM) to estimate food choice using liking, valence, and arousal as possible predictors. For this analysis, we used an existing data set comprised of liking and food-evoked emotions scores from 123 participants, who rated 7 unlabeled breakfast drinks. Liking scores were measured using a 100-mm visual analogue scale, while food-evoked emotions were measured using 2 existing emotion-profiling methods: a verbal and a non-verbal method (EsSense Profile and PrEmo, respectively). After 7 days, participants were asked to choose 1 breakfast drink from the experiment to consume during breakfast in a simulated restaurant environment. Cross validation showed that we were able to correctly predict individualized food choice (1 out of 7 products) for over 50% of the participants. This number increased to nearly 80% when looking at the top 2 candidates. Model comparisons showed that evoked emotions better predict food choice than perceived liking alone. However, the strongest predictive strength was achieved by the combination of evoked emotions and liking. Furthermore we showed that non-verbal food-evoked emotion scores more accurately predict food choice than verbal food-evoked emotions scores.

  8. An excitatory paraventricular nucleus to AgRP neuron circuit that drives hunger.

    Science.gov (United States)

    Krashes, Michael J; Shah, Bhavik P; Madara, Joseph C; Olson, David P; Strochlic, David E; Garfield, Alastair S; Vong, Linh; Pei, Hongjuan; Watabe-Uchida, Mitsuko; Uchida, Naoshige; Liberles, Stephen D; Lowell, Bradford B

    2014-03-13

    Hunger is a hard-wired motivational state essential for survival. Agouti-related peptide (AgRP)-expressing neurons in the arcuate nucleus (ARC) at the base of the hypothalamus are crucial to the control of hunger. They are activated by caloric deficiency and, when naturally or artificially stimulated, they potently induce intense hunger and subsequent food intake. Consistent with their obligatory role in regulating appetite, genetic ablation or chemogenetic inhibition of AgRP neurons decreases feeding. Excitatory input to AgRP neurons is important in caloric-deficiency-induced activation, and is notable for its remarkable degree of caloric-state-dependent synaptic plasticity. Despite the important role of excitatory input, its source(s) has been unknown. Here, through the use of Cre-recombinase-enabled, cell-specific neuron mapping techniques in mice, we have discovered strong excitatory drive that, unexpectedly, emanates from the hypothalamic paraventricular nucleus, specifically from subsets of neurons expressing thyrotropin-releasing hormone (TRH) and pituitary adenylate cyclase-activating polypeptide (PACAP, also known as ADCYAP1). Chemogenetic stimulation of these afferent neurons in sated mice markedly activates AgRP neurons and induces intense feeding. Conversely, acute inhibition in mice with caloric-deficiency-induced hunger decreases feeding. Discovery of these afferent neurons capable of triggering hunger advances understanding of how this intense motivational state is regulated.

  9. Assessment of pain sensitivity in patients with deep bite and sex- and age-matched controls

    DEFF Research Database (Denmark)

    Sonnesen, Ane Liselotte; Svensson, Peter

    2011-01-01

    AIMS: To compare pain sensitivity between deep bite patients and a sex- and age-matched control group with normal occlusion. METHODS: Pain sensitivity was assessed by injections of the excitatory amino acid glutamate into the masseter and brachioradialis muscles. Intensity of glutamate-evoked pai...... of gender-related differences in somatosensory sensitivity and for the first time indicate that subjects with deep bite may be more sensitive to glutamate-evoked pain and thermal stimuli.......AIMS: To compare pain sensitivity between deep bite patients and a sex- and age-matched control group with normal occlusion. METHODS: Pain sensitivity was assessed by injections of the excitatory amino acid glutamate into the masseter and brachioradialis muscles. Intensity of glutamate-evoked pain...

  10. The effect of STDP temporal kernel structure on the learning dynamics of single excitatory and inhibitory synapses.

    Directory of Open Access Journals (Sweden)

    Yotam Luz

    Full Text Available Spike-Timing Dependent Plasticity (STDP is characterized by a wide range of temporal kernels. However, much of the theoretical work has focused on a specific kernel - the "temporally asymmetric Hebbian" learning rules. Previous studies linked excitatory STDP to positive feedback that can account for the emergence of response selectivity. Inhibitory plasticity was associated with negative feedback that can balance the excitatory and inhibitory inputs. Here we study the possible computational role of the temporal structure of the STDP. We represent the STDP as a superposition of two processes: potentiation and depression. This allows us to model a wide range of experimentally observed STDP kernels, from Hebbian to anti-Hebbian, by varying a single parameter. We investigate STDP dynamics of a single excitatory or inhibitory synapse in purely feed-forward architecture. We derive a mean-field-Fokker-Planck dynamics for the synaptic weight and analyze the effect of STDP structure on the fixed points of the mean field dynamics. We find a phase transition along the Hebbian to anti-Hebbian parameter from a phase that is characterized by a unimodal distribution of the synaptic weight, in which the STDP dynamics is governed by negative feedback, to a phase with positive feedback characterized by a bimodal distribution. The critical point of this transition depends on general properties of the STDP dynamics and not on the fine details. Namely, the dynamics is affected by the pre-post correlations only via a single number that quantifies its overlap with the STDP kernel. We find that by manipulating the STDP temporal kernel, negative feedback can be induced in excitatory synapses and positive feedback in inhibitory. Moreover, there is an exact symmetry between inhibitory and excitatory plasticity, i.e., for every STDP rule of inhibitory synapse there exists an STDP rule for excitatory synapse, such that their dynamics is identical.

  11. Conscious wireless electroretinogram and visual evoked potentials in rats.

    Directory of Open Access Journals (Sweden)

    Jason Charng

    Full Text Available The electroretinogram (ERG, retina and visual evoked potential (VEP, brain are widely used in vivo tools assaying the integrity of the visual pathway. Current recordings in preclinical models are conducted under anesthesia, which alters neural physiology and contaminates responses. We describe a conscious wireless ERG and VEP recording platform in rats. Using a novel surgical technique to chronically implant electrodes subconjunctivally on the eye and epidurally over the visual cortex, we are able to record stable and repeatable conscious ERG and VEP signals over at least 1 month. We show that the use of anaesthetics, necessary for conventional ERG and VEP measurements, alters electrophysiology recordings. Conscious visual electrophysiology improves the viability of longitudinal studies by eliminating complications associated with repeated anaesthesia. It will also enable uncontaminated assessment of drug effects, allowing the eye to be used as an effective biomarker of the central nervous system.

  12. Dynamic excitatory and inhibitory gain modulation can produce flexible, robust and optimal decision-making.

    Directory of Open Access Journals (Sweden)

    Ritwik K Niyogi

    Full Text Available Behavioural and neurophysiological studies in primates have increasingly shown the involvement of urgency signals during the temporal integration of sensory evidence in perceptual decision-making. Neuronal correlates of such signals have been found in the parietal cortex, and in separate studies, demonstrated attention-induced gain modulation of both excitatory and inhibitory neurons. Although previous computational models of decision-making have incorporated gain modulation, their abstract forms do not permit an understanding of the contribution of inhibitory gain modulation. Thus, the effects of co-modulating both excitatory and inhibitory neuronal gains on decision-making dynamics and behavioural performance remain unclear. In this work, we incorporate time-dependent co-modulation of the gains of both excitatory and inhibitory neurons into our previous biologically based decision circuit model. We base our computational study in the context of two classic motion-discrimination tasks performed in animals. Our model shows that by simultaneously increasing the gains of both excitatory and inhibitory neurons, a variety of the observed dynamic neuronal firing activities can be replicated. In particular, the model can exhibit winner-take-all decision-making behaviour with higher firing rates and within a significantly more robust model parameter range. It also exhibits short-tailed reaction time distributions even when operating near a dynamical bifurcation point. The model further shows that neuronal gain modulation can compensate for weaker recurrent excitation in a decision neural circuit, and support decision formation and storage. Higher neuronal gain is also suggested in the more cognitively demanding reaction time than in the fixed delay version of the task. Using the exact temporal delays from the animal experiments, fast recruitment of gain co-modulation is shown to maximize reward rate, with a timescale that is surprisingly near the

  13. Characterization of music-evoked autobiographical memories.

    Science.gov (United States)

    Janata, Petr; Tomic, Stefan T; Rakowski, Sonja K

    2007-11-01

    Despite music's prominence in Western society and its importance to individuals in their daily lives, very little is known about the memories and emotions that are often evoked when hearing a piece of music from one's past. We examined the content of music-evoked autobiographical memories (MEAMs) using a novel approach for selecting stimuli from a large corpus of popular music, in both laboratory and online settings. A set of questionnaires probed the cognitive and affective properties of the evoked memories. On average, 30% of the song presentations evoked autobiographical memories, and the majority of songs also evoked various emotions, primarily positive, that were felt strongly. The third most common emotion was nostalgia. Analyses of written memory reports found both general and specific levels of autobiographical knowledge to be represented, and several social and situational contexts for memory formation were common across many memories. The findings indicate that excerpts of popular music serve as potent stimuli for studying the structure of autobiographical memories.

  14. Ryanodine receptors contribute to the induction of nociceptive input-evoked long-term potentiation in the rat spinal cord slice

    Directory of Open Access Journals (Sweden)

    Zhao Zhi-Qi

    2010-01-01

    Full Text Available Abstract Background Our previous study demonstrated that nitric oxide (NO contributes to long-term potentiation (LTP of C-fiber-evoked field potentials by tetanic stimulation of the sciatic nerve in the spinal cord in vivo. Ryanodine receptor (RyR is a downstream target for NO. The present study further explored the role of RyR in synaptic plasticity of the spinal pain pathway. Results By means of field potential recordings in the adult male rat in vivo, we showed that RyR antagonist reduced LTP of C-fiber-evoked responses in the spinal dorsal horn by tetanic stimulation of the sciatic nerve. Using spinal cord slice preparations and field potential recordings from superficial dorsal horn, high frequency stimulation of Lissauer's tract (LT stably induced LTP of field excitatory postsynaptic potentials (fEPSPs. Perfusion of RyR antagonists blocked the induction of LT stimulation-evoked spinal LTP, while Ins(1,4,5P3 receptor (IP3R antagonist had no significant effect on LTP induction. Moreover, activation of RyRs by caffeine without high frequency stimulation induced a long-term potentiation in the presence of bicuculline methiodide and strychnine. Further, in patch-clamp recordings from superficial dorsal horn neurons, activation of RyRs resulted in a large increase in the frequency of miniature EPSCs (mEPSCs. Immunohistochemical study showed that RyRs were expressed in the dorsal root ganglion (DRG neurons. Likewise, calcium imaging in small DRG neurons illustrated that activation of RyRs elevated [Ca2+]i in small DRG neurons. Conclusions These data indicate that activation of presynaptic RyRs play a crucial role in the induction of LTP in the spinal pain pathway, probably through enhancement of transmitter release.

  15. Effects of dimethylarsinic and dimethylarsinous acid on evoked synaptic potentials in hippocampal slices of young and adult rats

    International Nuclear Information System (INIS)

    Krueger, Katharina; Repges, Hendrik; Hippler, Joerg; Hartmann, Louise M.; Hirner, Alfred V.; Straub, Heidrun; Binding, Norbert; Musshoff, Ulrich

    2007-01-01

    In this study, the effects of pentavalent dimethylarsinic acid ((CH 3 ) 2 AsO(OH); DMA V ) and trivalent dimethylarsinous acid ((CH 3 ) 2 As(OH); DMA III ) on synaptic transmission generated by the excitatory Schaffer collateral-CA1 synapse were tested in hippocampal slices of young (14-21 day-old) and adult (2-4 month-old) rats. Both compounds were applied in concentrations of 1 to 100 μmol/l. DMA V had no effect on the amplitudes of evoked fEPSPs or the induction of LTP recorded from the CA1 dendritic region either in adult or in young rats. However, application of DMA III significantly reduced the amplitudes of evoked fEPSPs in a concentration-dependent manner with a total depression following application of 100 μmol/l DMA III in adult and 10 μmol/l DMA III in young rats. Moreover, DMA III significantly affected the LTP-induction. Application of 10 μmol/l DMA III resulted in a complete failure of the postsynaptic potentiation of the fEPSP amplitudes in slices taken both from adult and young rats. The depressant effect was not reversible after a 30-min washout of the DMA III . In slices of young rats, the depressant effects of DMA III were more pronounced than in those taken from adult ones. Compared to the (absent) effect of DMA V on synaptic transmission, the trivalent compound possesses a considerably higher neurotoxic potential

  16. Intermittent Hypoxia Enhances Functional Connectivity of Midcervical Spinal Interneurons

    Science.gov (United States)

    Streeter, Kristi A.; Sunshine, Michael D.; Patel, Shreya; Gonzalez-Rothi, Elisa J.; Reier, Paul J.

    2017-01-01

    Brief, intermittent oxygen reductions [acute intermittent hypoxia (AIH)] evokes spinal plasticity. Models of AIH-induced neuroplasticity have focused on motoneurons; however, most midcervical interneurons (C-INs) also respond to hypoxia. We hypothesized that AIH would alter the functional connectivity between C-INs and induce persistent changes in discharge. Bilateral phrenic nerve activity was recorded in anesthetized and ventilated adult male rats and a multielectrode array was used to record C4/5 spinal discharge before [baseline (BL)], during, and 15 min after three 5 min hypoxic episodes (11% O2, H1–H3). Most C-INs (94%) responded to hypoxia by either increasing or decreasing firing rate. Functional connectivity was examined by cross-correlating C-IN discharge. Correlograms with a peak or trough were taken as evidence for excitatory or inhibitory connectivity between C-IN pairs. A subset of C-IN pairs had increased excitatory cross-correlations during hypoxic episodes (34%) compared with BL (19%; p phrenic motoneurons and excitatory inputs to these “pre-phrenic” cells increased during AIH. We conclude that AIH alters connectivity of the midcervical spinal network. To our knowledge, this is the first demonstration that AIH induces plasticity within the propriospinal network. SIGNIFICANCE STATEMENT Acute intermittent hypoxia (AIH) can trigger spinal plasticity associated with sustained increases in respiratory, somatic, and/or autonomic motor output. The impact of AIH on cervical spinal interneuron (C-IN) discharge and connectivity is unknown. Our results demonstrate that AIH recruits excitatory C-INs into the spinal respiratory (phrenic) network. AIH also enhances excitatory and reduces inhibitory connections among the C-IN network. We conclude that C-INs are part of the respiratory, somatic, and/or autonomic response to AIH, and that propriospinal plasticity may contribute to sustained increases in motor output after AIH. PMID:28751456

  17. Parallel prefrontal pathways reach distinct excitatory and inhibitory systems in memory-related rhinal cortices.

    Science.gov (United States)

    Bunce, Jamie G; Zikopoulos, Basilis; Feinberg, Marcia; Barbas, Helen

    2013-12-15

    To investigate how prefrontal cortices impinge on medial temporal cortices we labeled pathways from the anterior cingulate cortex (ACC) and posterior orbitofrontal cortex (pOFC) in rhesus monkeys to compare their relationship with excitatory and inhibitory systems in rhinal cortices. The ACC pathway terminated mostly in areas 28 and 35 with a high proportion of large terminals, whereas the pOFC pathway terminated mostly through small terminals in area 36 and sparsely in areas 28 and 35. Both pathways terminated in all layers. Simultaneous labeling of pathways and distinct neurochemical classes of inhibitory neurons, followed by analyses of appositions of presynaptic and postsynaptic fluorescent signal, or synapses, showed overall predominant association with spines of putative excitatory neurons, but also significant interactions with presumed inhibitory neurons labeled for calretinin, calbindin, or parvalbumin. In the upper layers of areas 28 and 35 the ACC pathway was associated with dendrites of neurons labeled with calretinin, which are thought to disinhibit neighboring excitatory neurons, suggesting facilitated hippocampal access. In contrast, in area 36 pOFC axons were associated with dendrites of calbindin neurons, which are poised to reduce noise and enhance signal. In the deep layers, both pathways innervated mostly dendrites of parvalbumin neurons, which strongly inhibit neighboring excitatory neurons, suggesting gating of hippocampal output to other cortices. These findings suggest that the ACC, associated with attention and context, and the pOFC, associated with emotional valuation, have distinct contributions to memory in rhinal cortices, in processes that are disrupted in psychiatric diseases. Copyright © 2013 Wiley Periodicals, Inc.

  18. Transmission to interneurons is via slow excitatory synaptic potentials mediated by P2Y(1 receptors during descending inhibition in guinea-pig ileum.

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    Peter D J Thornton

    Full Text Available BACKGROUND: The nature of synaptic transmission at functionally distinct synapses in intestinal reflex pathways has not been fully identified. In this study, we investigated whether transmission between interneurons in the descending inhibitory pathway is mediated by a purine acting at P2Y receptors to produce slow excitatory synaptic potentials (EPSPs. METHODOLOGY/PRINCIPAL FINDINGS: Myenteric neurons from guinea-pig ileum in vitro were impaled with intracellular microelectrodes. Responses to distension 15 mm oral to the recording site, in a separately perfused stimulation chamber and to electrical stimulation of local nerve trunks were recorded. A subset of neurons, previously identified as nitric oxide synthase immunoreactive descending interneurons, responded to both stimuli with slow EPSPs that were reversibly abolished by a high concentration of PPADS (30 μM, P2 receptor antagonist. When added to the central chamber of a three chambered organ bath, PPADS concentration-dependently depressed transmission through that chamber of descending inhibitory reflexes, measured as inhibitory junction potentials in the circular muscle of the anal chamber. Reflexes evoked by distension in the central chamber were unaffected. A similar depression of transmission was seen when the specific P2Y(1 receptor antagonist MRS 2179 (10 μM was in the central chamber. Blocking either nicotinic receptors (hexamethonium 200 μM or 5-HT(3 receptors (granisetron 1 μM together with P2 receptors had no greater effect than blocking P2 receptors alone. CONCLUSIONS/SIGNIFICANCE: Slow EPSPs mediated by P2Y(1 receptors, play a primary role in transmission between descending interneurons of the inhibitory reflexes in the guinea-pig ileum. This is the first demonstration for a primary role of excitatory metabotropic receptors in physiological transmission at a functionally identified synapse.

  19. Raclopride or high-frequency stimulation of the subthalamic nucleus stops cocaine-induced motor stereotypy and restores related alterations in prefrontal basal ganglia circuits.

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    Aliane, Verena; Pérez, Sylvie; Deniau, Jean-Michel; Kemel, Marie-Louise

    2012-11-01

    Motor stereotypy is a key symptom of various neurological or neuropsychiatric disorders. Neuroleptics or the promising treatment using deep brain stimulation stops stereotypies but the mechanisms underlying their actions are unclear. In rat, motor stereotypies are linked to an imbalance between prefrontal and sensorimotor cortico-basal ganglia circuits. Indeed, cortico-nigral transmission was reduced in the prefrontal but not sensorimotor basal ganglia circuits and dopamine and acetylcholine release was altered in the prefrontal but not sensorimotor territory of the dorsal striatum. Furthermore, cholinergic transmission in the prefrontal territory of the dorsal striatum plays a crucial role in the arrest of motor stereotypy. Here we found that, as previously observed for raclopride, high-frequency stimulation of the subthalamic nucleus (HFS STN) rapidly stopped cocaine-induced motor stereotypies in rat. Importantly, raclopride and HFS STN exerted a strong effect on cocaine-induced alterations in prefrontal basal ganglia circuits. Raclopride restored the cholinergic transmission in the prefrontal territory of the dorsal striatum and the cortico-nigral information transmissions in the prefrontal basal ganglia circuits. HFS STN also restored the N-methyl-d-aspartic-acid-evoked release of acetylcholine and dopamine in the prefrontal territory of the dorsal striatum. However, in contrast to raclopride, HFS STN did not restore the cortico-substantia nigra pars reticulata transmissions but exerted strong inhibitory and excitatory effects on neuronal activity in the prefrontal subdivision of the substantia nigra pars reticulata. Thus, both raclopride and HFS STN stop cocaine-induced motor stereotypy, but exert different effects on the related alterations in the prefrontal basal ganglia circuits. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  20. Unsupervised discrimination of patterns in spiking neural networks with excitatory and inhibitory synaptic plasticity.

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    Srinivasa, Narayan; Cho, Youngkwan

    2014-01-01

    A spiking neural network model is described for learning to discriminate among spatial patterns in an unsupervised manner. The network anatomy consists of source neurons that are activated by external inputs, a reservoir that resembles a generic cortical layer with an excitatory-inhibitory (EI) network and a sink layer of neurons for readout. Synaptic plasticity in the form of STDP is imposed on all the excitatory and inhibitory synapses at all times. While long-term excitatory STDP enables sparse and efficient learning of the salient features in inputs, inhibitory STDP enables this learning to be stable by establishing a balance between excitatory and inhibitory currents at each neuron in the network. The synaptic weights between source and reservoir neurons form a basis set for the input patterns. The neural trajectories generated in the reservoir due to input stimulation and lateral connections between reservoir neurons can be readout by the sink layer neurons. This activity is used for adaptation of synapses between reservoir and sink layer neurons. A new measure called the discriminability index (DI) is introduced to compute if the network can discriminate between old patterns already presented in an initial training session. The DI is also used to compute if the network adapts to new patterns without losing its ability to discriminate among old patterns. The final outcome is that the network is able to correctly discriminate between all patterns-both old and new. This result holds as long as inhibitory synapses employ STDP to continuously enable current balance in the network. The results suggest a possible direction for future investigation into how spiking neural networks could address the stability-plasticity question despite having continuous synaptic plasticity.

  1. Electrical stimulation of dog pudendal nerve regulates the excitatory pudendal-to-bladder reflex

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    Yan-he Ju

    2016-01-01

    Full Text Available Pudendal nerve plays an important role in urine storage and voiding. Our hypothesis is that a neuroprosthetic device placed in the pudendal nerve trunk can modulate bladder function after suprasacral spinal cord injury. We had confirmed the inhibitory pudendal-to-bladder reflex by stimulating either the branch or the trunk of the pudendal nerve. This study explored the excitatory pudendal-to-bladder reflex in beagle dogs, with intact or injured spinal cord, by electrical stimulation of the pudendal nerve trunk. The optimal stimulation frequency was approximately 15-25 Hz. This excitatory effect was dependent to some extent on the bladder volume. We conclude that stimulation of the pudendal nerve trunk is a promising method to modulate bladder function.

  2. Traveling wave front solutions in lateral-excitatory neuronal networks

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    Sittipong Ruktamatakul

    2008-05-01

    Full Text Available In this paper, we discuss the shape of traveling wave front solutions to a neuronal model with the connection function to be of lateral excitation type. This means that close connecting cells have an inhibitory influence, while cells that aremore distant have an excitatory influence. We give results on the shape of the wave fronts solutions, which exhibit different shapes depend ing on the size of a threshold parameter.

  3. GABAergic activities control spike timing- and frequency-dependent long-term depression at hippocampal excitatory synapses

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    Makoto Nishiyama

    2010-06-01

    Full Text Available GABAergic interneuronal network activities in the hippocampus control a variety of neural functions, including learning and memory, by regulating θ and γ oscillations. How these GABAergic activities at pre- and post-synaptic sites of hippocampal CA1 pyramidal cells differentially contribute to synaptic function and plasticity during their repetitive pre- and post-synaptic spiking at θ and γ oscillations is largely unknown. We show here that activities mediated by postsynaptic GABAARs and presynaptic GABABRs determine, respectively, the spike timing- and frequency-dependence of activity-induced synaptic modifications at Schaffer collateral-CA1 excitatory synapses. We demonstrate that both feedforward and feedback GABAAR-mediated inhibition in the postsynaptic cell controls the spike timing-dependent long-term depression of excitatory inputs (“e-LTD” at the θ frequency. We also show that feedback postsynaptic inhibition specifically causes e-LTD of inputs that induce small postsynaptic currents (<70 pA with LTP timing, thus enforcing the requirement of cooperativity for induction of long-term potentiation at excitatory inputs (“e-LTP”. Furthermore, under spike-timing protocols that induce e-LTP and e-LTD at excitatory synapses, we observed parallel induction of LTP and LTD at inhibitory inputs (“i-LTP” and “i-LTD” to the same postsynaptic cells. Finally, we show that presynaptic GABABR-mediated inhibition plays a major role in the induction of frequency-dependent e-LTD at α and β frequencies. These observations demonstrate the critical influence of GABAergic interneuronal network activities in regulating the spike timing and frequency dependences of long-term synaptic modifications in the hippocampus.

  4. Glucose rapidly induces different forms of excitatory synaptic plasticity in hypothalamic POMC neurons.

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    Jun Hu

    Full Text Available Hypothalamic POMC neurons are required for glucose and energy homeostasis. POMC neurons have a wide synaptic connection with neurons both within and outside the hypothalamus, and their activity is controlled by a balance between excitatory and inhibitory synaptic inputs. Brain glucose-sensing plays an essential role in the maintenance of normal body weight and metabolism; however, the effect of glucose on synaptic transmission in POMC neurons is largely unknown. Here we identified three types of POMC neurons (EPSC(+, EPSC(-, and EPSC(+/- based on their glucose-regulated spontaneous excitatory postsynaptic currents (sEPSCs, using whole-cell patch-clamp recordings. Lowering extracellular glucose decreased the frequency of sEPSCs in EPSC(+ neurons, but increased it in EPSC(- neurons. Unlike EPSC(+ and EPSC(- neurons, EPSC(+/- neurons displayed a bi-phasic sEPSC response to glucoprivation. In the first phase of glucoprivation, both the frequency and the amplitude of sEPSCs decreased, whereas in the second phase, they increased progressively to the levels above the baseline values. Accordingly, lowering glucose exerted a bi-phasic effect on spontaneous action potentials in EPSC(+/- neurons. Glucoprivation decreased firing rates in the first phase, but increased them in the second phase. These data indicate that glucose induces distinct excitatory synaptic plasticity in different subpopulations of POMC neurons. This synaptic remodeling is likely to regulate the sensitivity of the melanocortin system to neuronal and hormonal signals.

  5. Glucose rapidly induces different forms of excitatory synaptic plasticity in hypothalamic POMC neurons.

    Science.gov (United States)

    Hu, Jun; Jiang, Lin; Low, Malcolm J; Rui, Liangyou

    2014-01-01

    Hypothalamic POMC neurons are required for glucose and energy homeostasis. POMC neurons have a wide synaptic connection with neurons both within and outside the hypothalamus, and their activity is controlled by a balance between excitatory and inhibitory synaptic inputs. Brain glucose-sensing plays an essential role in the maintenance of normal body weight and metabolism; however, the effect of glucose on synaptic transmission in POMC neurons is largely unknown. Here we identified three types of POMC neurons (EPSC(+), EPSC(-), and EPSC(+/-)) based on their glucose-regulated spontaneous excitatory postsynaptic currents (sEPSCs), using whole-cell patch-clamp recordings. Lowering extracellular glucose decreased the frequency of sEPSCs in EPSC(+) neurons, but increased it in EPSC(-) neurons. Unlike EPSC(+) and EPSC(-) neurons, EPSC(+/-) neurons displayed a bi-phasic sEPSC response to glucoprivation. In the first phase of glucoprivation, both the frequency and the amplitude of sEPSCs decreased, whereas in the second phase, they increased progressively to the levels above the baseline values. Accordingly, lowering glucose exerted a bi-phasic effect on spontaneous action potentials in EPSC(+/-) neurons. Glucoprivation decreased firing rates in the first phase, but increased them in the second phase. These data indicate that glucose induces distinct excitatory synaptic plasticity in different subpopulations of POMC neurons. This synaptic remodeling is likely to regulate the sensitivity of the melanocortin system to neuronal and hormonal signals.

  6. Differentiated human midbrain-derived neural progenitor cells express excitatory strychnine-sensitive glycine receptors containing α2β subunits.

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    Florian Wegner

    Full Text Available BACKGROUND: Human fetal midbrain-derived neural progenitor cells (NPCs may deliver a tissue source for drug screening and regenerative cell therapy to treat Parkinson's disease. While glutamate and GABA(A receptors play an important role in neurogenesis, the involvement of glycine receptors during human neurogenesis and dopaminergic differentiation as well as their molecular and functional characteristics in NPCs are largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: Here we investigated NPCs in respect to their glycine receptor function and subunit expression using electrophysiology, calcium imaging, immunocytochemistry, and quantitative real-time PCR. Whole-cell recordings demonstrate the ability of NPCs to express functional strychnine-sensitive glycine receptors after differentiation for 3 weeks in vitro. Pharmacological and molecular analyses indicate a predominance of glycine receptor heteromers containing α2β subunits. Intracellular calcium measurements of differentiated NPCs suggest that glycine evokes depolarisations mediated by strychnine-sensitive glycine receptors and not by D-serine-sensitive excitatory glycine receptors. Culturing NPCs with additional glycine, the glycine-receptor antagonist strychnine, or the Na(+-K(+-Cl(- co-transporter 1 (NKCC1-inhibitor bumetanide did not significantly influence cell proliferation and differentiation in vitro. CONCLUSIONS/SIGNIFICANCE: These data indicate that NPCs derived from human fetal midbrain tissue acquire essential glycine receptor properties during neuronal maturation. However, glycine receptors seem to have a limited functional impact on neurogenesis and dopaminergic differentiation of NPCs in vitro.

  7. Beyond the evoked/intrinsic neural process dichotomy

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    Taylor Bolt

    2018-03-01

    Full Text Available Contemporary functional neuroimaging research has increasingly focused on characterization of intrinsic or “spontaneous” brain activity. Analysis of intrinsic activity is often contrasted with analysis of task-evoked activity that has traditionally been the focus of cognitive neuroscience. But does this evoked/intrinsic dichotomy adequately characterize human brain function? Based on empirical data demonstrating a close functional interdependence between intrinsic and task-evoked activity, we argue that the dichotomy between intrinsic and task-evoked activity as unobserved contributions to brain activity is artificial. We present an alternative picture of brain function in which the brain’s spatiotemporal dynamics do not consist of separable intrinsic and task-evoked components, but reflect the enaction of a system of mutual constraints to move the brain into and out of task-appropriate functional configurations. According to this alternative picture, cognitive neuroscientists are tasked with describing both the temporal trajectory of brain activity patterns across time, and the modulation of this trajectory by task states, without separating this process into intrinsic and task-evoked components. We argue that this alternative picture of brain function is best captured in a novel explanatory framework called enabling constraint. Overall, these insights call for a reconceptualization of functional brain activity, and should drive future methodological and empirical efforts.

  8. Secondhand tobacco smoke exposure differentially alters nucleus tractus solitarius neurons at two different ages in developing non-human primates

    International Nuclear Information System (INIS)

    Sekizawa, Shin-ichi; Joad, Jesse P.; Pinkerton, Kent E.; Bonham, Ann C.

    2010-01-01

    Exposing children to secondhand tobacco smoke (SHS) is associated with increased risk for asthma, bronchiolitis and SIDS. The role for changes in the developing CNS contributing to these problems has not been fully explored. We used rhesus macaques to test the hypothesis that SHS exposure during development triggers neuroplastic changes in the nucleus tractus solitarius (NTS), where lung sensory information related to changes in airway and lung function is first integrated. Pregnant monkeys were exposed to filtered air (FA) or SHS for 6 h/day, 5 days/week starting at 50-day gestational age. Mother/infant pairs continued the exposures postnatally to age 3 or 13 months, which may be equivalent to approximately 1 or 4 years of human age, respectively. Whole-cell recordings were made of second-order NTS neurons in transverse brainstem slices. To target the consequences of SHS exposure based on neuronal subgroups, we classified NTS neurons into two phenotypes, rapid-onset spiking (RS) and delayed-onset spiking (DS), and then evaluated intrinsic and synaptic excitabilities in FA-exposed animals. RS neurons showed greater cell excitability especially at age of 3 months while DS neurons received greater amplitudes of excitatory postsynaptic currents (EPSCs). Developmental neuroplasticity such as increases in intrinsic and synaptic excitabilities were detected especially in DS neurons. In 3 month olds, SHS exposure effects were limited to excitatory changes in RS neurons, specifically increases in evoked EPSC amplitudes and increased spiking responses accompanied by shortened action potential width. By 13 months, the continued SHS exposure inhibited DS neuronal activity; decreases in evoked EPSC amplitudes and blunted spiking responses accompanied by prolonged action potential width. The influence of SHS exposure on age-related and phenotype specific changes may be associated with age-specific respiratory problems, for which SHS exposure can increase the risk, such as SIDS

  9. Carbamazepine and oxcarbazepine, but not eslicarbazepine, enhance excitatory synaptic transmission onto hippocampal CA1 pyramidal cells through an antagonist action at adenosine A1 receptors.

    Science.gov (United States)

    Booker, Sam A; Pires, Nuno; Cobb, Stuart; Soares-da-Silva, Patrício; Vida, Imre

    2015-06-01

    This study assessed the anticonvulsant and seizure generation effects of carbamazepine (CBZ), oxcarbazepine (OXC) and eslicarbazepine (S-Lic) in wild-type mice. Electrophysiological recordings were made to discriminate potential cellular and synaptic mechanisms underlying anti- and pro-epileptic actions. The anticonvulsant and pro-convulsant effects were evaluated in the MES, the 6-Hz and the Irwin tests. Whole-cell patch-clamp recordings were used to investigate the effects on fast excitatory and inhibitory synaptic transmission in hippocampal area CA1. The safety window for CBZ, OXC and eslicarbazepine (ED50 value against the MES test and the dose that produces grade 5 convulsions in all mice), was 6.3, 6.0 and 12.5, respectively. At high concentrations the three drugs reduced synaptic transmission. CBZ and OXC enhanced excitatory postsynaptic currents (EPSCs) at low, therapeutically-relevant concentrations. These effects were associated with no change in inhibitory postsynaptic currents (IPSCs) resulting in altered balance between excitation and inhibition. S-Lic had no effect on EPSC or IPSC amplitudes over the same concentration range. The CBZ mediated enhancement of EPSCs was blocked by DPCPX, a selective antagonist, and occluded by CCPA, a selective agonist of the adenosine A1 receptor. Furthermore, reduction of endogenous adenosine by application of the enzyme adenosine deaminase also abolished the CBZ- and OXC-induced increase of EPSCs, indicating that the two drugs act as antagonists at native adenosine receptors. In conclusion, CBZ and OXC possess pro-epileptic actions at clinically-relevant concentrations through the enhancement of excitatory synaptic transmission. S-Lic by comparison has no such effect on synaptic transmission, explaining its lack of seizure exacerbation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Excitatory/inhibitory imbalance in autism spectrum disorders: Implications for interventions and therapeutics.

    Science.gov (United States)

    Uzunova, Genoveva; Pallanti, Stefano; Hollander, Eric

    2016-04-01

    Imbalance between excitation and inhibition and increased excitatory-inhibitory (E-I) ratio is a common mechanism in autism spectrum disorders (ASD) that is responsible for the learning and memory, cognitive, sensory, motor deficits, and seizures occurring in these disorders. ASD are very heterogeneous and better understanding of E-I imbalance in brain will lead to better diagnosis and treatments. We perform a critical literature review of the causes and presentations of E-I imbalance in ASD. E-I imbalance in ASD is due primarily to abnormal glutamatergic and GABAergic neurotransmission in key brain regions such as neocortex, hippocampus, amygdala, and cerebellum. Other causes are due to dysfunction of neuropeptides (oxytocin), synaptic proteins (neuroligins), and immune system molecules (cytokines). At the neuropathological level E-I imbalance in ASD is presented as a "minicolumnopathy". E-I imbalance alters the manner by which the brain processes information and regulates behaviour. New developments for investigating E-I imbalance such as optogenetics and transcranial magnetic stimulation (TMS) are presented. Non-invasive brain stimulation methods such as TMS for treatment of the core symptoms of ASD are discussed. Understanding E-I imbalance has important implications for developing better pharmacological and behavioural treatments for ASD, including TMS, new drugs, biomarkers and patient stratification.

  11. Glycine receptors support excitatory neurotransmitter release in developing mouse visual cortex

    Science.gov (United States)

    Kunz, Portia A; Burette, Alain C; Weinberg, Richard J; Philpot, Benjamin D

    2012-01-01

    Glycine receptors (GlyRs) are found in most areas of the brain, and their dysfunction can cause severe neurological disorders. While traditionally thought of as inhibitory receptors, presynaptic-acting GlyRs (preGlyRs) can also facilitate glutamate release under certain circumstances, although the underlying molecular mechanisms are unknown. In the current study, we sought to better understand the role of GlyRs in the facilitation of excitatory neurotransmitter release in mouse visual cortex. Using whole-cell recordings, we found that preGlyRs facilitate glutamate release in developing, but not adult, visual cortex. The glycinergic enhancement of neurotransmitter release in early development depends on the high intracellular to extracellular Cl− gradient maintained by the Na+–K+–2Cl− cotransporter and requires Ca2+ entry through voltage-gated Ca2+ channels. The glycine transporter 1, localized to glial cells, regulates extracellular glycine concentration and the activation of these preGlyRs. Our findings demonstrate a developmentally regulated mechanism for controlling excitatory neurotransmitter release in the neocortex. PMID:22988142

  12. GABA(B) receptor modulation of feedforward inhibition through hippocampal neurogliaform cells.

    Science.gov (United States)

    Price, Christopher J; Scott, Ricardo; Rusakov, Dmitri A; Capogna, Marco

    2008-07-02

    Feedforward inhibition of neurons is a fundamental component of information flow control in the brain. We studied the roles played by neurogliaform cells (NGFCs) of stratum lacunosum moleculare of the hippocampus in providing feedforward inhibition to CA1 pyramidal cells. We recorded from synaptically coupled pairs of anatomically identified NGFCs and CA1 pyramidal cells and found that, strikingly, a single presynaptic action potential evoked a biphasic unitary IPSC (uIPSC), consisting of two distinct components mediated by GABA(A) and GABA(B) receptors. A GABA(B) receptor-mediated unitary response has not previously been observed in hippocampal excitatory neurons. The decay of the GABA(A) receptor-mediated response was slow (time constant = 50 ms), and was tightly regulated by presynaptic GABA(B) receptors. Surprisingly, the GABA(B) receptor ligands baclofen and (2S)-3-{[(1S)-1-(3,4-dichlorophenyl)ethyl]amino-2-hydroxypropyl}(phenylmethyl)phosphinic acid (CGP55845), while affecting the NGFC-mediated uIPSCs, had no effect on action potential-evoked presynaptic Ca2+ signals monitored in individual axonal boutons of NGFCs with two-photon microscopy. In contrast, baclofen clearly depressed presynaptic Ca2+ transients in non-NGF interneurons. Changes in extracellular Ca2+ concentration that mimicked the effects of baclofen or CGP55845 on uIPSCs significantly altered presynaptic Ca2+ transients. Electrophysiological data suggest that GABA(B) receptors expressed by NGFCs contribute to the dynamic control of the excitatory input to CA1 pyramidal neurons from the temporoammonic path. The NGFC-CA1 pyramidal cell connection therefore provides a unique and subtle mechanism to shape the integration time domain for signals arriving via a major excitatory input to CA1 pyramidal cells.

  13. Normalization of auditory evoked potential and visual evoked potential in patients with idiot savant.

    Science.gov (United States)

    Chen, X; Zhang, M; Wang, J; Lou, F; Liang, J

    1999-03-01

    To investigate the variations of auditory evoked potentials (AEP) and visual evoked potentials (VEP) of patients with idiot savant (IS) syndrome. Both AEP and VEP were recorded from 7 patients with IS syndrome, 21 mentally retarded (MR) children without the syndrome and 21 normally age-matched controls, using a Dantec concerto SEEG-16 BEAM instrument. Both AEP and VEP of MR group showed significantly longer latencies (P1 and P2 latencies of AEP, P savant syndrome presented normalized AEP and VEP.

  14. Age-related decreased inhibitory vs. excitatory gene expression in the adult autistic brain

    NARCIS (Netherlands)

    van de Lagemaat, Louie N; Nijhof, Bonnie; Bosch, Daniëlle G M; Kohansal-Nodehi, Mahdokht; Keerthikumar, Shivakumar; Heimel, J.A.

    2014-01-01

    Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by impaired social interaction and communication, and restricted behavior and interests. A disruption in the balance of excitatory and inhibitory neurotransmission has been hypothesized to underlie these disorders. Here

  15. Intrinsically-generated fluctuating activity in excitatory-inhibitory networks

    Science.gov (United States)

    Mastrogiuseppe, Francesca; Ostojic, Srdjan

    2017-01-01

    Recurrent networks of non-linear units display a variety of dynamical regimes depending on the structure of their synaptic connectivity. A particularly remarkable phenomenon is the appearance of strongly fluctuating, chaotic activity in networks of deterministic, but randomly connected rate units. How this type of intrinsically generated fluctuations appears in more realistic networks of spiking neurons has been a long standing question. To ease the comparison between rate and spiking networks, recent works investigated the dynamical regimes of randomly-connected rate networks with segregated excitatory and inhibitory populations, and firing rates constrained to be positive. These works derived general dynamical mean field (DMF) equations describing the fluctuating dynamics, but solved these equations only in the case of purely inhibitory networks. Using a simplified excitatory-inhibitory architecture in which DMF equations are more easily tractable, here we show that the presence of excitation qualitatively modifies the fluctuating activity compared to purely inhibitory networks. In presence of excitation, intrinsically generated fluctuations induce a strong increase in mean firing rates, a phenomenon that is much weaker in purely inhibitory networks. Excitation moreover induces two different fluctuating regimes: for moderate overall coupling, recurrent inhibition is sufficient to stabilize fluctuations; for strong coupling, firing rates are stabilized solely by the upper bound imposed on activity, even if inhibition is stronger than excitation. These results extend to more general network architectures, and to rate networks receiving noisy inputs mimicking spiking activity. Finally, we show that signatures of the second dynamical regime appear in networks of integrate-and-fire neurons. PMID:28437436

  16. Glucose Rapidly Induces Different Forms of Excitatory Synaptic Plasticity in Hypothalamic POMC Neurons

    Science.gov (United States)

    Hu, Jun; Jiang, Lin; Low, Malcolm J.; Rui, Liangyou

    2014-01-01

    Hypothalamic POMC neurons are required for glucose and energy homeostasis. POMC neurons have a wide synaptic connection with neurons both within and outside the hypothalamus, and their activity is controlled by a balance between excitatory and inhibitory synaptic inputs. Brain glucose-sensing plays an essential role in the maintenance of normal body weight and metabolism; however, the effect of glucose on synaptic transmission in POMC neurons is largely unknown. Here we identified three types of POMC neurons (EPSC(+), EPSC(−), and EPSC(+/−)) based on their glucose-regulated spontaneous excitatory postsynaptic currents (sEPSCs), using whole-cell patch-clamp recordings. Lowering extracellular glucose decreased the frequency of sEPSCs in EPSC(+) neurons, but increased it in EPSC(−) neurons. Unlike EPSC(+) and EPSC(−) neurons, EPSC(+/−) neurons displayed a bi-phasic sEPSC response to glucoprivation. In the first phase of glucoprivation, both the frequency and the amplitude of sEPSCs decreased, whereas in the second phase, they increased progressively to the levels above the baseline values. Accordingly, lowering glucose exerted a bi-phasic effect on spontaneous action potentials in EPSC(+/−) neurons. Glucoprivation decreased firing rates in the first phase, but increased them in the second phase. These data indicate that glucose induces distinct excitatory synaptic plasticity in different subpopulations of POMC neurons. This synaptic remodeling is likely to regulate the sensitivity of the melanocortin system to neuronal and hormonal signals. PMID:25127258

  17. Visually Evoked Spiking Evolves While Spontaneous Ongoing Dynamics Persist

    Science.gov (United States)

    Huys, Raoul; Jirsa, Viktor K.; Darokhan, Ziauddin; Valentiniene, Sonata; Roland, Per E.

    2016-01-01

    Neurons in the primary visual cortex spontaneously spike even when there are no visual stimuli. It is unknown whether the spiking evoked by visual stimuli is just a modification of the spontaneous ongoing cortical spiking dynamics or whether the spontaneous spiking state disappears and is replaced by evoked spiking. This study of laminar recordings of spontaneous spiking and visually evoked spiking of neurons in the ferret primary visual cortex shows that the spiking dynamics does not change: the spontaneous spiking as well as evoked spiking is controlled by a stable and persisting fixed point attractor. Its existence guarantees that evoked spiking return to the spontaneous state. However, the spontaneous ongoing spiking state and the visual evoked spiking states are qualitatively different and are separated by a threshold (separatrix). The functional advantage of this organization is that it avoids the need for a system reorganization following visual stimulation, and impedes the transition of spontaneous spiking to evoked spiking and the propagation of spontaneous spiking from layer 4 to layers 2–3. PMID:26778982

  18. The distribution of excitatory amino acid receptors on acutely dissociated dorsal horn neurons from postnatal rats.

    Science.gov (United States)

    Arancio, O; Yoshimura, M; Murase, K; MacDermott, A B

    1993-01-01

    Excitatory amino acid receptor distribution was mapped on acutely dissociated neurons from postnatal rat spinal cord dorsal horn. N-methyl D-aspartate, quisqualate and kainate were applied to multiple locations along the somal and dendritic surfaces of voltage-clamped neurons by means of a pressure application system. To partially compensate for the decrement of response amplitude due to current loss between the site of activation on the dendrite and the recording electrode at the soma, a solution containing 0.15 M KCl was applied on the cell bodies and dendrites of some cells to estimate an empirical length constant. In the majority of the cells tested, the dendritic membrane had regions of higher sensitivity to excitatory amino acid agonists than the somatic membrane, with dendritic response amplitudes reaching more than seven times those at the cell body. A comparison of the relative changes in sensitivity between each combination of two of the three excitatory amino acid agonists along the same dendrite showed different patterns of agonist sensitivity along the dendrite in the majority of the cells. These data were obtained from dorsal horn neurons that had developed and formed synaptic connections in vivo. They demonstrate that in contrast to observations made on ventral horn neurons, receptor density for all the excitatory amino acid receptors on dorsal horn neurons, including the N-methyl-D-aspartate receptor, are generally higher on the dendrites than on the soma. Further, these results are similar to those obtained from dorsal horn neurons grown in culture.

  19. Brain-immune interaction accompanying odor-evoked autobiographic memory.

    Science.gov (United States)

    Matsunaga, Masahiro; Bai, Yu; Yamakawa, Kaori; Toyama, Asako; Kashiwagi, Mitsuyoshi; Fukuda, Kazuyuki; Oshida, Akiko; Sanada, Kazue; Fukuyama, Seisuke; Shinoda, Jun; Yamada, Jitsuhiro; Sadato, Norihiro; Ohira, Hideki

    2013-01-01

    The phenomenon in which a certain smell evokes a specific memory is known as the Proust phenomenon. Odor-evoked autobiographic memories are more emotional than those elicited by other sensory stimuli. The results of our previous study indicated that odor-evoked autobiographic memory accompanied by positive emotions has remarkable effects on various psychological and physiological activities, including the secretion of cytokines, which are immune-signaling molecules that modulate systemic inflammation. In this study, we aimed to clarify the neural substrates associated with the interaction between odor-evoked autobiographic memory and peripheral circulating cytokines. We recruited healthy male and female volunteers and investigated the association between brain responses and the concentration of several cytokines in the plasma by using positron emission tomography (PET) recordings when an autographic memory was evoked in participants by asking them to smell an odor that was nostalgic to them. Participants experienced positive emotions and autobiographic memories when nostalgic odors were presented to them. The levels of peripheral proinflammatory cytokines, such as the tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), were significantly reduced after experiencing odor-evoked autobiographic memory. Subtraction analysis of PET images indicated that the medial orbitofrontal cortex (mOFC) and precuneus/posterior cingulate cortex (PCC) were significantly activated during experiences of odor-evoked autobiographic memory. Furthermore, a correlation analysis indicated that activities of the mOFC and precuneus/PCC were negatively correlated with IFN-γ concentration. These results indicate that the neural networks including the precuneus/PCC and mOFC might regulate the secretion of peripheral proinflammatory cytokines during the experience of odor-evoked autobiographic memories accompanied with positive emotions.

  20. Brain–Immune Interaction Accompanying Odor-Evoked Autobiographic Memory

    Science.gov (United States)

    Matsunaga, Masahiro; Bai, Yu; Yamakawa, Kaori; Toyama, Asako; Kashiwagi, Mitsuyoshi; Fukuda, Kazuyuki; Oshida, Akiko; Sanada, Kazue; Fukuyama, Seisuke; Shinoda, Jun; Yamada, Jitsuhiro; Sadato, Norihiro; Ohira, Hideki

    2013-01-01

    The phenomenon in which a certain smell evokes a specific memory is known as the Proust phenomenon. Odor-evoked autobiographic memories are more emotional than those elicited by other sensory stimuli. The results of our previous study indicated that odor-evoked autobiographic memory accompanied by positive emotions has remarkable effects on various psychological and physiological activities, including the secretion of cytokines, which are immune-signaling molecules that modulate systemic inflammation. In this study, we aimed to clarify the neural substrates associated with the interaction between odor-evoked autobiographic memory and peripheral circulating cytokines. We recruited healthy male and female volunteers and investigated the association between brain responses and the concentration of several cytokines in the plasma by using positron emission tomography (PET) recordings when an autographic memory was evoked in participants by asking them to smell an odor that was nostalgic to them. Participants experienced positive emotions and autobiographic memories when nostalgic odors were presented to them. The levels of peripheral proinflammatory cytokines, such as the tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), were significantly reduced after experiencing odor-evoked autobiographic memory. Subtraction analysis of PET images indicated that the medial orbitofrontal cortex (mOFC) and precuneus/posterior cingulate cortex (PCC) were significantly activated during experiences of odor-evoked autobiographic memory. Furthermore, a correlation analysis indicated that activities of the mOFC and precuneus/PCC were negatively correlated with IFN-γ concentration. These results indicate that the neural networks including the precuneus/PCC and mOFC might regulate the secretion of peripheral proinflammatory cytokines during the experience of odor-evoked autobiographic memories accompanied with positive emotions. PMID:23977312

  1. Brain-immune interaction accompanying odor-evoked autobiographic memory.

    Directory of Open Access Journals (Sweden)

    Masahiro Matsunaga

    Full Text Available The phenomenon in which a certain smell evokes a specific memory is known as the Proust phenomenon. Odor-evoked autobiographic memories are more emotional than those elicited by other sensory stimuli. The results of our previous study indicated that odor-evoked autobiographic memory accompanied by positive emotions has remarkable effects on various psychological and physiological activities, including the secretion of cytokines, which are immune-signaling molecules that modulate systemic inflammation. In this study, we aimed to clarify the neural substrates associated with the interaction between odor-evoked autobiographic memory and peripheral circulating cytokines. We recruited healthy male and female volunteers and investigated the association between brain responses and the concentration of several cytokines in the plasma by using positron emission tomography (PET recordings when an autographic memory was evoked in participants by asking them to smell an odor that was nostalgic to them. Participants experienced positive emotions and autobiographic memories when nostalgic odors were presented to them. The levels of peripheral proinflammatory cytokines, such as the tumor necrosis factor-α (TNF-α and interferon-γ (IFN-γ, were significantly reduced after experiencing odor-evoked autobiographic memory. Subtraction analysis of PET images indicated that the medial orbitofrontal cortex (mOFC and precuneus/posterior cingulate cortex (PCC were significantly activated during experiences of odor-evoked autobiographic memory. Furthermore, a correlation analysis indicated that activities of the mOFC and precuneus/PCC were negatively correlated with IFN-γ concentration. These results indicate that the neural networks including the precuneus/PCC and mOFC might regulate the secretion of peripheral proinflammatory cytokines during the experience of odor-evoked autobiographic memories accompanied with positive emotions.

  2. Dynamical responses to external stimuli for both cases of excitatory and inhibitory synchronization in a complex neuronal network.

    Science.gov (United States)

    Kim, Sang-Yoon; Lim, Woochang

    2017-10-01

    For studying how dynamical responses to external stimuli depend on the synaptic-coupling type, we consider two types of excitatory and inhibitory synchronization (i.e., synchronization via synaptic excitation and inhibition) in complex small-world networks of excitatory regular spiking (RS) pyramidal neurons and inhibitory fast spiking (FS) interneurons. For both cases of excitatory and inhibitory synchronization, effects of synaptic couplings on dynamical responses to external time-periodic stimuli S ( t ) (applied to a fraction of neurons) are investigated by varying the driving amplitude A of S ( t ). Stimulated neurons are phase-locked to external stimuli for both cases of excitatory and inhibitory couplings. On the other hand, the stimulation effect on non-stimulated neurons depends on the type of synaptic coupling. The external stimulus S ( t ) makes a constructive effect on excitatory non-stimulated RS neurons (i.e., it causes external phase lockings in the non-stimulated sub-population), while S ( t ) makes a destructive effect on inhibitory non-stimulated FS interneurons (i.e., it breaks up original inhibitory synchronization in the non-stimulated sub-population). As results of these different effects of S ( t ), the type and degree of dynamical response (e.g., synchronization enhancement or suppression), characterized by the dynamical response factor [Formula: see text] (given by the ratio of synchronization degree in the presence and absence of stimulus), are found to vary in a distinctly different way, depending on the synaptic-coupling type. Furthermore, we also measure the matching degree between the dynamics of the two sub-populations of stimulated and non-stimulated neurons in terms of a "cross-correlation" measure [Formula: see text]. With increasing A , based on [Formula: see text], we discuss the cross-correlations between the two sub-populations, affecting the dynamical responses to S ( t ).

  3. Cortical stimulation evokes abnormal responses in the dopamine-depleted rat basal ganglia.

    Science.gov (United States)

    Kita, Hitoshi; Kita, Takako

    2011-07-13

    The motor cortex (MC) sends massive projections to the basal ganglia. Motor disabilities in patients and animal models of Parkinson's disease (PD) may be caused by dopamine (DA)-depleted basal ganglia that abnormally process the information originating from MC. To study how DA depletion alters signal transfer in the basal ganglia, MC stimulation-induced (MC-induced) unitary responses were recorded from the basal ganglia of control and 6-hydroxydopamine-treated hemi-parkinsonian rats anesthetized with isoflurane. This report describes new findings about how DA depletion alters MC-induced responses. MC stimulation evokes an excitation in normally quiescent striatal (Str) neurons projecting to the globus pallidus external segment (GPe). After DA-depletion, the spontaneous firing of Str-GPe neurons increases, and MC stimulation evokes a shorter latency excitation followed by a long-lasting inhibition that was invisible under normal conditions. The increased firing activity and the newly exposed long inhibition generate tonic inhibition and a disfacilitation in GPe. The disfacilitation in GPe is then amplified in basal ganglia circuitry and generates a powerful long inhibition in the basal ganglia output nucleus, the globus pallidus internal segment. Intra-Str injections of a behaviorally effective dose of DA precursor l-3,4-dihydroxyphenylalanine effectively reversed these changes. These newly observed mechanisms also support the generation of pauses and burst activity commonly observed in the basal ganglia of parkinsonian subjects. These results suggest that the generation of abnormal response sequences in the basal ganglia contributes to the development of motor disabilities in PD and that intra-Str DA supplements effectively suppress abnormal signal transfer.

  4. Cholinergic Inputs from Basal Forebrain Add an Excitatory Bias to Odor Coding in the Olfactory Bulb

    Science.gov (United States)

    Rothermel, Markus; Carey, Ryan M.; Puche, Adam; Shipley, Michael T.

    2014-01-01

    Cholinergic modulation of central circuits is associated with active sensation, attention, and learning, yet the neural circuits and temporal dynamics underlying cholinergic effects on sensory processing remain unclear. Understanding the effects of cholinergic modulation on particular circuits is complicated by the widespread projections of cholinergic neurons to telencephalic structures that themselves are highly interconnected. Here we examined how cholinergic projections from basal forebrain to the olfactory bulb (OB) modulate output from the first stage of sensory processing in the mouse olfactory system. By optogenetically activating their axons directly in the OB, we found that cholinergic projections from basal forebrain regulate OB output by increasing the spike output of presumptive mitral/tufted cells. Cholinergic stimulation increased mitral/tufted cell spiking in the absence of inhalation-driven sensory input and further increased spiking responses to inhalation of odorless air and to odorants. This modulation was rapid and transient, was dependent on local cholinergic signaling in the OB, and differed from modulation by optogenetic activation of cholinergic neurons in basal forebrain, which led to a mixture of mitral/tufted cell excitation and suppression. Finally, bulbar cholinergic enhancement of mitral/tufted cell odorant responses was robust and occurred independent of the strength or even polarity of the odorant-evoked response, indicating that cholinergic modulation adds an excitatory bias to mitral/tufted cells as opposed to increasing response gain or sharpening response spectra. These results are consistent with a role for the basal forebrain cholinergic system in dynamically regulating the sensitivity to or salience of odors during active sensing of the olfactory environment. PMID:24672011

  5. Intracortical inhibitory and excitatory circuits in subjects with minimal hepatic encephalopathy: a TMS study.

    Science.gov (United States)

    Nardone, Raffaele; De Blasi, Pierpaolo; Höller, Yvonne; Brigo, Francesco; Golaszewski, Stefan; Frey, Vanessa N; Orioli, Andrea; Trinka, Eugen

    2016-10-01

    Minimal hepatic encephalopathy (MHE) is the earliest form of hepatic encephalopathy (HE) and affects up to 80 % of patients with liver cirrhosis. By definition, MHE is characterized by psychomotor slowing and subtle cognitive deficits,  but obvious clinical manifestations are lacking. Given its covert nature, MHE is often underdiagnosed. This study was aimed at detecting neurophysiological changes, as assessed by means of transcranial magnetic stimulation (TMS), involved in the early pathogenesis of the HE. We investigated motor cortex excitability in 15 patients with MHE and in 15 age-matched age-matched cirrhotic patients without MHE; the resting motor threshold, the short-interval intracortical inhibition (SICI) and the intracortical facilitation (ICF) were examined. Paired-pulse TMS revealed significant increased SICI and reduced ICF in the patients with MHE. These findings may reflect abnormalities in intrinsic brain activity and altered organization of functional connectivity networks. In particular, the results suggest a shift in the balance between intracortical inhibitory and excitatory mechanisms towards a net increase of inhibitory neurotransmission. Together with other neurophysiological (in particular EEG) and neuroimaging techniques, TMS may thus provide early markers of cerebral dysfunction in cirrhotic patients with MHE.

  6. Habituation of evoked responses is greater in patients with familial hemiplegic migraine than in controls

    DEFF Research Database (Denmark)

    Hansen, Jakob Møller; Bolla, M; Magis, D

    2011-01-01

    have associated with disturbed ion homeostasis, altered cellular excitability, neurotransmitter release, and decreased threshold for cortical spreading depression. The common forms of migraine are characterized interictally by a habituation deficit of cortical and subcortical evoked responses that has...... been attributed to neuronal dysexcitability. FHM and the common forms of migraine are thought to belong to a spectrum of migraine phenotypes with similar pathophysiology, and we therefore examined whether an abnormal habituation pattern would also be found in FHM patients....

  7. Emergent spatial patterns of excitatory and inhibitory synaptic strengths drive somatotopic representational discontinuities and their plasticity in a computational model of primary sensory cortical area 3b

    Directory of Open Access Journals (Sweden)

    Kamil A. Grajski

    2016-07-01

    Full Text Available Mechanisms underlying the emergence and plasticity of representational discontinuities in the mammalian primary somatosensory cortical representation of the hand are investigated in a computational model. The model consists of an input lattice organized as a three-digit hand forward-connected to a lattice of cortical columns each of which contains a paired excitatory and inhibitory cell. Excitatory and inhibitory synaptic plasticity of feedforward and lateral connection weights is implemented as a simple covariance rule and competitive normalization. Receptive field properties are computed independently for excitatory and inhibitory cells and compared within and across columns. Within digit representational zones intracolumnar excitatory and inhibitory receptive field extents are concentric, single-digit, small, and unimodal. Exclusively in representational boundary-adjacent zones, intracolumnar excitatory and inhibitory receptive field properties diverge: excitatory cell receptive fields are single-digit, small, and unimodal; and the paired inhibitory cell receptive fields are bimodal, double-digit, and large. In simulated syndactyly (webbed fingers, boundary-adjacent intracolumnar receptive field properties reorganize to within-representation type; divergent properties are reacquired following syndactyly release. This study generates testable hypotheses for assessment of cortical laminar-dependent receptive field properties and plasticity within and between cortical representational zones. For computational studies, present results suggest that concurrent excitatory and inhibitory plasticity may underlie novel emergent properties.

  8. Effects of insomnia disorder and knee osteoarthritis on resting and pain-evoked inflammatory markers.

    Science.gov (United States)

    Quartana, Phillip J; Finan, Patrick H; Page, Gayle G; Smith, Michael T

    2015-07-01

    Osteoarthritis is the most prevalent arthritic condition. Systemic inflammatory cytokines appear to have an important role in the onset and maintenance of the disease. Sleep disturbances are prevalent in osteoarthritis and associated with alterations in systemic inflammatory cytokines, suggesting a common pathophysiology across these conditions. A comparative investigation of the effects of insomnia disorder and osteoarthritis on pain-evoked cytokine responses has yet to be undertaken. We examined the influence of symptomatic knee osteoarthritis and insomnia disorder on resting C-reactive protein (CRP), interleukin (IL)-6, and IL-10 levels, and pain-evoked IL-6 and IL-10 responses. Participants were N=117 older adults (mean age=59.7years; 61.8% women) rigorously evaluated for knee osteoarthritis and insomnia disorder using established diagnostic guidelines. Results revealed no association of osteoarthritis or insomnia disorder with CRP. Resting IL-6 was greater in osteoarthritis participants versus those without osteoarthritis, although this association was largely attributable to BMI. IL-10 was highest among participants with osteoarthritis or insomnia disorder. Growth curve modeling revealed that participants with insomnia disorder had greater pain-evoked IL-6 responses than participants without insomnia disorder or osteoarthritis. These findings highlight the utility of laboratory pain testing methods for understanding individual differences in inflammatory cytokines. Moreover, our findings provide evidence for amplified pain-evoked pro-inflammatory cytokine reactivity among older adults with clinically diagnosed insomnia disorder, even after controlling for individual differences in BMI and age. Additional research will be required determine whether an amplified pain-related cytokine response contributes to OA, and possibly other age-related disease, associated with insomnia disorder. Published by Elsevier Inc.

  9. Inhibitory neurons modulate spontaneous signaling in cultured cortical neurons: density-dependent regulation of excitatory neuronal signaling

    International Nuclear Information System (INIS)

    Serra, Michael; Guaraldi, Mary; Shea, Thomas B

    2010-01-01

    Cortical neuronal activity depends on a balance between excitatory and inhibitory influences. Culturing of neurons on multi-electrode arrays (MEAs) has provided insight into the development and maintenance of neuronal networks. Herein, we seeded MEAs with murine embryonic cortical/hippocampal neurons at different densities ( 1000 cells mm −2 ) and monitored resultant spontaneous signaling. Sparsely seeded cultures displayed a large number of bipolar, rapid, high-amplitude individual signals with no apparent temporal regularity. By contrast, densely seeded cultures instead displayed clusters of signals at regular intervals. These patterns were observed even within thinner and thicker areas of the same culture. GABAergic neurons (25% of total neurons in our cultures) mediated the differential signal patterns observed above, since addition of the inhibitory antagonist bicuculline to dense cultures and hippocampal slice cultures induced the signal pattern characteristic of sparse cultures. Sparsely seeded cultures likely lacked sufficient inhibitory neurons to modulate excitatory activity. Differential seeding of MEAs can provide a unique model for analyses of pertubation in the interaction between excitatory and inhibitory function during aging and neuropathological conditions where dysregulation of GABAergic neurons is a significant component

  10. Bilateral somatosensory evoked potentials following intermittent theta-burst repetitive transcranial magnetic stimulation.

    Science.gov (United States)

    Premji, Azra; Ziluk, Angela; Nelson, Aimee J

    2010-08-05

    Intermittent theta-burst stimulation (iTBS) is a form of repetitive transcranial magnetic stimulation that may alter cortical excitability in the primary somatosensory cortex (SI). The present study investigated the effects of iTBS on subcortical and early cortical somatosensory evoked potentials (SEPs) recorded over left, iTBS stimulated SI and the right-hemisphere non-stimulated SI. SEPs were recorded before and at 5, 15, and 25 minutes following iTBS. Compared to pre-iTBS, the amplitude of cortical potential N20/P25 was significantly increased for 5 minutes from non-stimulated SI and for 15 to 25 minutes from stimulated SI. Subcortical potentials recorded bilaterally remained unaltered following iTBS. We conclude that iTBS increases the cortical excitability of SI bilaterally and does not alter thalamocortical afferent input to SI. ITBS may provide one avenue to induce cortical plasticity in the somatosensory cortex.

  11. Deep brain stimulation of the amygdala alleviates fear conditioning-induced alterations in synaptic plasticity in the cortical-amygdala pathway and fear memory.

    Science.gov (United States)

    Sui, Li; Huang, SiJia; Peng, BinBin; Ren, Jie; Tian, FuYing; Wang, Yan

    2014-07-01

    Deep brain stimulation (DBS) of the amygdala has been demonstrated to modulate hyperactivity of the amygdala, which is responsible for the symptoms of post-traumatic stress disorder (PTSD), and thus might be used for the treatment of PTSD. However, the underlying mechanism of DBS of the amygdala in the modulation of the amygdala is unclear. The present study investigated the effects of DBS of the amygdala on synaptic transmission and synaptic plasticity at cortical inputs to the amygdala, which is critical for the formation and storage of auditory fear memories, and fear memories. The results demonstrated that auditory fear conditioning increased single-pulse-evoked field excitatory postsynaptic potentials in the cortical-amygdala pathway. Furthermore, auditory fear conditioning decreased the induction of paired-pulse facilitation and long-term potentiation, two neurophysiological models for studying short-term and long-term synaptic plasticity, respectively, in the cortical-amygdala pathway. In addition, all these auditory fear conditioning-induced changes could be reversed by DBS of the amygdala. DBS of the amygdala also rescued auditory fear conditioning-induced enhancement of long-term retention of fear memory. These findings suggested that DBS of the amygdala alleviating fear conditioning-induced alterations in synaptic plasticity in the cortical-amygdala pathway and fear memory may underlie the neuromodulatory role of DBS of the amygdala in activities of the amygdala.

  12. DEVELOPMENTAL HYPOTHYROIDISM ALTERS SYNAPTIC TRANSMISSION IN DENTATE GYRUS AND AREA CA1 OF HIPPOCAMPUS.

    Science.gov (United States)

    Hypothyroidism during critical periods of brain developmental leads to learning deficits and alterations in hippocampal structure. Neurophysiological properties of the hippocampus, however, have not been well characterized. The present study examined field potentials evoked in...

  13. Central pathway for spontaneous and prostaglandin E2-evoked cutaneous vasoconstriction.

    Science.gov (United States)

    Rathner, Joseph A; Madden, Christopher J; Morrison, Shaun F

    2008-07-01

    A reduction of heat loss to the environment through increased cutaneous vasoconstrictor (CVC) sympathetic outflow contributes to elevated body temperature during fever. We determined the role of neurons in the dorsomedial hypothalamus (DMH) in increases in CVC sympathetic tone evoked by PGE2 into the preoptic area (POA) in chloralose/urethane-anesthetized rats. The frequency of axonal action potentials of CVC sympathetic ganglion cells recorded from the surface of the tail artery was increased by 1.8 Hz following nanoinjections of bicuculline (50 pmol) into the DMH. PGE2 nanoinjection into the POA elicited a similar excitation of tail CVC neurons (+2.1 Hz). Subsequent to PGE2 into the POA, muscimol (400 pmol/side) into the DMH did not alter the activity of tail CVC neurons. Inhibition of neurons in the rostral raphé pallidus (rRPa) eliminated the spontaneous discharge of tail CVC neurons but only reduced the PGE2-evoked activity. Residual activity was abolished by subsequent muscimol into the rostral ventrolateral medulla. Transections through the neuraxis caudal to the POA increased the activity of tail CVC neurons, which were sustained through transections caudal to DMH. We conclude that while activation of neurons in the DMH is sufficient to activate tail CVC neurons, it is not necessary for their PGE2-evoked activity. These results support a CVC component of increased core temperature elicited by PGE2 in POA that arises from relief of a tonic inhibition from neurons in POA of CVC sympathetic premotor neurons in rRPa and is dependent on the excitation of CVC premotor neurons from a site caudal to DMH.

  14. Towards a neural basis of music-evoked emotions.

    Science.gov (United States)

    Koelsch, Stefan

    2010-03-01

    Music is capable of evoking exceptionally strong emotions and of reliably affecting the mood of individuals. Functional neuroimaging and lesion studies show that music-evoked emotions can modulate activity in virtually all limbic and paralimbic brain structures. These structures are crucially involved in the initiation, generation, detection, maintenance, regulation and termination of emotions that have survival value for the individual and the species. Therefore, at least some music-evoked emotions involve the very core of evolutionarily adaptive neuroaffective mechanisms. Because dysfunctions in these structures are related to emotional disorders, a better understanding of music-evoked emotions and their neural correlates can lead to a more systematic and effective use of music in therapy. Copyright 2010 Elsevier Ltd. All rights reserved.

  15. Enhanced excitatory input to MCH neurons during developmental period of high food intake is mediated by GABA

    Science.gov (United States)

    Li, Ying; van den Pol, Anthony N.

    2010-01-01

    In contrast to the local axons of GABA neurons of the cortex and hippocampus, lateral hypothalamic neurons containing melanin concentrating hormone (MCH) and GABA send long axons throughout the brain and play key roles in energy homeostasis and mental status. In adults, MCH neurons maintain a hyperpolarized membrane potential and most of the synaptic input is inhibitory. In contrast, we found that developing MCH neurons received substantially more excitatory synaptic input. Based on gramicidicin-perforated patch recordings in hypothalamic slices from MCH-GFP transgenic mice, we found that GABA was the primary excitatory synaptic transmitter in embryonic and neonatal ages up to postnatal day 10. Surprisingly, glutamate assumed only a minor excitatory role, if any. GABA plays a complex role in developing MCH neurons, with its actions conditionally dependent on a number of factors. GABA depolarization could lead to an increase in spikes either independently or in summation with other depolarizing stimuli, or alternately, depending on the relative timing of other depolarizing events, could lead to shunting inhibition. The developmental shift from depolarizing to hyperpolarizing occurred later in the dendrites than in the cell body. Early GABA depolarization was based on a Cl− dependent inward current. An interesting secondary depolarization in mature neurons that followed an initial hyperpolarization was based on a bicarbonate mechanism. Thus during the early developmental period when food consumption is high, MCH neurons are more depolarized than in the adult, and an increased level of excitatory synaptic input to these orexigenic cells is mediated by GABA. PMID:19955372

  16. Electrical vestibular stimulation after vestibular deafferentation and in vestibular schwannoma.

    Directory of Open Access Journals (Sweden)

    Swee Tin Aw

    Full Text Available BACKGROUND: Vestibular reflexes, evoked by human electrical (galvanic vestibular stimulation (EVS, are utilized to assess vestibular function and investigate its pathways. Our study aimed to investigate the electrically-evoked vestibulo-ocular reflex (eVOR output after bilateral and unilateral vestibular deafferentations to determine the characteristics for interpreting unilateral lesions such as vestibular schwannomas. METHODS: EVOR was recorded with dual-search coils as binocular three-dimensional eye movements evoked by bipolar 100 ms-step at EVS intensities of [0.9, 2.5, 5.0, 7.5, 10.0] mA and unipolar 100 ms-step at 5 mA EVS intensity. Five bilateral vestibular deafferented (BVD, 12 unilateral vestibular deafferented (UVD, four unilateral vestibular schwannoma (UVS patients and 17 healthy subjects were tested with bipolar EVS, and five UVDs with unipolar EVS. RESULTS: After BVD, bipolar EVS elicited no eVOR. After UVD, bipolar EVS of one functioning ear elicited bidirectional, excitatory eVOR to cathodal EVS with 9 ms latency and inhibitory eVOR to anodal EVS, opposite in direction, at half the amplitude with 12 ms latency, exhibiting an excitatory-inhibitory asymmetry. The eVOR patterns from UVS were consistent with responses from UVD confirming the vestibular loss on the lesion side. Unexpectedly, unipolar EVS of the UVD ear, instead of absent response, evoked one-third the bipolar eVOR while unipolar EVS of the functioning ear evoked half the bipolar response. CONCLUSIONS: The bidirectional eVOR evoked by bipolar EVS from UVD with an excitatory-inhibitory asymmetry and the 3 ms latency difference between normal and lesion side may be useful for detecting vestibular lesions such as UVS. We suggest that current spread could account for the small eVOR to 5 mA unipolar EVS of the UVD ear.

  17. Neonatal seizures alter NMDA glutamate receptor GluN2A and 3A subunit expression and function in hippocampal CA1 neurons

    Science.gov (United States)

    Zhou, Chengwen; Sun, Hongyu; Klein, Peter M.; Jensen, Frances E.

    2015-01-01

    Neonatal seizures are commonly caused by hypoxic and/or ischemic injury during birth and can lead to long-term epilepsy and cognitive deficits. In a rodent hypoxic seizure (HS) model, we have previously demonstrated a critical role for seizure-induced enhancement of the AMPA subtype of glutamate receptor (GluA) in epileptogenesis and cognitive consequences, in part due to GluA maturational upregulation of expression. Similarly, as the expression and function of the N-Methyl-D-aspartate (NMDA) subtype of glutamate receptor (GluN) is also developmentally controlled, we examined how early life seizures during the critical period of synaptogenesis could modify GluN development and function. In a postnatal day (P)10 rat model of neonatal seizures, we found that seizures could alter GluN2/3 subunit composition of GluNs and physiological function of synaptic GluNs. In hippocampal slices removed from rats within 48–96 h following seizures, the amplitudes of synaptic GluN-mediated evoked excitatory postsynaptic currents (eEPSCs) were elevated in CA1 pyramidal neurons. Moreover, GluN eEPSCs showed a decreased sensitivity to GluN2B selective antagonists and decreased Mg2+ sensitivity at negative holding potentials, indicating a higher proportion of GluN2A and GluN3A subunit function, respectively. These physiological findings were accompanied by a concurrent increase in GluN2A phosphorylation and GluN3A protein. These results suggest that altered GluN function and expression could potentially contribute to future epileptogenesis following neonatal seizures, and may represent potential therapeutic targets for the blockade of future epileptogenesis in the developing brain. PMID:26441533

  18. Dexmedetomidine decreases inhibitory but not excitatory neurotransmission to cardiac vagal neurons in the nucleus ambiguus.

    Science.gov (United States)

    Sharp, Douglas B; Wang, Xin; Mendelowitz, David

    2014-07-29

    Dexmedetomidine, an α2 adrenergic agonist, is a useful sedative but can also cause significant bradycardia. This decrease in heart rate may be due to decreased central sympathetic output as well as increased parasympathetic output from brainstem cardiac vagal neurons. In this study, using whole cell voltage clamp methodology, the actions of dexmedetomidine on excitatory glutamatergic and inhibitory GABAergic and glycinergic neurotransmission to parasympathetic cardiac vagal neurons in the rat nucleus ambiguus was determined. The results indicate that dexmedetomidine decreases both GABAergic and glycinergic inhibitory input to cardiac vagal neurons, with no significant effect on excitatory input. These results provide a mechanism for dexmedetomidine induced bradycardia and has implications for the management of this potentially harmful side effect. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Alterations in Brain Inflammation, Synaptic Proteins, and Adult Hippocampal Neurogenesis during Epileptogenesis in Mice Lacking Synapsin2.

    Directory of Open Access Journals (Sweden)

    Deepti Chugh

    Full Text Available Synapsins are pre-synaptic vesicle-associated proteins linked to the pathogenesis of epilepsy through genetic association studies in humans. Deletion of synapsins causes an excitatory/inhibitory imbalance, exemplified by the epileptic phenotype of synapsin knockout mice. These mice develop handling-induced tonic-clonic seizures starting at the age of about 3 months. Hence, they provide an opportunity to study epileptogenic alterations in a temporally controlled manner. Here, we evaluated brain inflammation, synaptic protein expression, and adult hippocampal neurogenesis in the epileptogenic (1 and 2 months of age and tonic-clonic (3.5-4 months phase of synapsin 2 knockout mice using immunohistochemical and biochemical assays. In the epileptogenic phase, region-specific microglial activation was evident, accompanied by an increase in the chemokine receptor CX3CR1, interleukin-6, and tumor necrosis factor-α, and a decrease in chemokine keratinocyte chemoattractant/ growth-related oncogene. Both post-synaptic density-95 and gephyrin, scaffolding proteins at excitatory and inhibitory synapses, respectively, showed a significant up-regulation primarily in the cortex. Furthermore, we observed an increase in the inhibitory adhesion molecules neuroligin-2 and neurofascin and potassium chloride co-transporter KCC2. Decreased expression of γ-aminobutyric acid receptor-δ subunit and cholecystokinin was also evident. Surprisingly, hippocampal neurogenesis was reduced in the epileptogenic phase. Taken together, we report molecular alterations in brain inflammation and excitatory/inhibitory balance that could serve as potential targets for therapeutics and diagnostic biomarkers. In addition, the regional differences in brain inflammation and synaptic protein expression indicate an epileptogenic zone from where the generalized seizures in synapsin 2 knockout mice may be initiated or spread.

  20. Chronic intermittent hypoxia-hypercapnia blunts heart rate responses and alters neurotransmission to cardiac vagal neurons.

    Science.gov (United States)

    Dyavanapalli, Jhansi; Jameson, Heather; Dergacheva, Olga; Jain, Vivek; Alhusayyen, Mona; Mendelowitz, David

    2014-07-01

    Patients with obstructive sleep apnoea experience chronic intermittent hypoxia-hypercapnia (CIHH) during sleep that elicit sympathetic overactivity and diminished parasympathetic activity to the heart, leading to hypertension and depressed baroreflex sensitivity. The parasympathetic control of heart rate arises from pre-motor cardiac vagal neurons (CVNs) located in nucleus ambiguus (NA) and dorsal motor nucleus of the vagus (DMNX). The mechanisms underlying diminished vagal control of heart rate were investigated by studying the changes in blood pressure, heart rate, and neurotransmission to CVNs evoked by acute hypoxia-hypercapnia (H-H) and CIHH. In vivo telemetry recordings of blood pressure and heart rate were obtained in adult rats during 4 weeks of CIHH exposure. Retrogradely labelled CVNs were identified in an in vitro brainstem slice preparation obtained from adult rats exposed either to air or CIHH for 4 weeks. Postsynaptic inhibitory or excitatory currents were recorded using whole cell voltage clamp techniques. Rats exposed to CIHH had increases in blood pressure, leading to hypertension, and blunted heart rate responses to acute H-H. CIHH induced an increase in GABAergic and glycinergic neurotransmission to CVNs in NA and DMNX, respectively; and a reduction in glutamatergic neurotransmission to CVNs in both nuclei. CIHH blunted the bradycardia evoked by acute H-H and abolished the acute H-H evoked inhibition of GABAergic transmission while enhancing glycinergic neurotransmission to CVNs in NA. These changes with CIHH inhibit CVNs and vagal outflow to the heart, both in acute and chronic exposures to H-H, resulting in diminished levels of cardioprotective parasympathetic activity to the heart as seen in OSA patients. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

  1. Postural threat differentially affects the feedforward and feedback components of the vestibular-evoked balance response.

    Science.gov (United States)

    Osler, Callum J; Tersteeg, M C A; Reynolds, Raymond F; Loram, Ian D

    2013-10-01

    Circumstances may render the consequence of falling quite severe, thus maximising the motivation to control postural sway. This commonly occurs when exposed to height and may result from the interaction of many factors, including fear, arousal, sensory information and perception. Here, we examined human vestibular-evoked balance responses during exposure to a highly threatening postural context. Nine subjects stood with eyes closed on a narrow walkway elevated 3.85 m above ground level. This evoked an altered psycho-physiological state, demonstrated by a twofold increase in skin conductance. Balance responses were then evoked by galvanic vestibular stimulation. The sway response, which comprised a whole-body lean in the direction of the edge of the walkway, was significantly and substantially attenuated after ~800 ms. This demonstrates that a strong reason to modify the balance control strategy was created and subjects were highly motivated to minimise sway. Despite this, the initial response remained unchanged. This suggests little effect on the feedforward settings of the nervous system responsible for coupling pure vestibular input to functional motor output. The much stronger, later effect can be attributed to an integration of balance-relevant sensory feedback once the body was in motion. These results demonstrate that the feedforward and feedback components of a vestibular-evoked balance response are differently affected by postural threat. Although a fear of falling has previously been linked with instability and even falling itself, our findings suggest that this relationship is not attributable to changes in the feedforward vestibular control of balance. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  2. Bilateral somatosensory evoked potentials following intermittent theta-burst repetitive transcranial magnetic stimulation

    Directory of Open Access Journals (Sweden)

    Ziluk Angela

    2010-08-01

    Full Text Available Abstract Background Intermittent theta-burst stimulation (iTBS is a form of repetitive transcranial magnetic stimulation that may alter cortical excitability in the primary somatosensory cortex (SI. The present study investigated the effects of iTBS on subcortical and early cortical somatosensory evoked potentials (SEPs recorded over left, iTBS stimulated SI and the right-hemisphere non-stimulated SI. SEPs were recorded before and at 5, 15, and 25 minutes following iTBS. Results Compared to pre-iTBS, the amplitude of cortical potential N20/P25 was significantly increased for 5 minutes from non-stimulated SI and for 15 to 25 minutes from stimulated SI. Subcortical potentials recorded bilaterally remained unaltered following iTBS. Conclusion We conclude that iTBS increases the cortical excitability of SI bilaterally and does not alter thalamocortical afferent input to SI. ITBS may provide one avenue to induce cortical plasticity in the somatosensory cortex.

  3. Spontaneous and evoked cerebral activity modifications on whole-body γ irradiated adult rabbit

    International Nuclear Information System (INIS)

    Court, L.; Dufour, R.; Bassant, M.H.; Fatome, M.

    1976-01-01

    Whole-body γ-exposure from 150 to 850 rads (dose-rate: 14 rads.min -1 ) delivered to adult rabbits chronically implanted with electrodes resulted in prompt and delayed changes of behavior, arousal and spontaneous and evoked electrical activities. Electrophysiological techniques of polygraphic recording and signal processing showed that the alterations were related to the absorbed dose. The threshold dose accompanied with transient changes of arousal should be in the range of 50-100 rads; below this range, to the exclusion of some possible behavior changes, exposure should act as a stimulation that would become nociceptive at higher doses only [fr

  4. Psychological and physiological responses to odor-evoked autobiographic memory.

    Science.gov (United States)

    Matsunaga, Masahiro; Isowa, Tokiko; Yamakawa, Kaori; Kawanishi, Yoko; Tsuboi, Hirohito; Kaneko, Hiroshi; Sadato, Norihiro; Oshida, Akiko; Katayama, Atsushi; Kashiwagi, Mitsuyoshi; Ohira, Hideki

    2011-01-01

    The "Proust phenomenon" occurs when a certain smell evokes a specific memory. Recent studies have demonstrated that odor-evoked autobiographic memories are more emotional than those elicited by other sensory stimuli because of the direct neural communication between the olfactory system and the amygdala. The amygdala is known to regulate various physiological activities including the endocrine and immune systems; therefore, odor-evoked autobiographic memory may trigger various psychological and physiological responses; however, the responses elicited by this memory remains obscure. In this study, we aimed to investigate the psychological and physiological responses accompanying odor-evoked autobiographic memory. We recruited healthy male and female volunteers and investigated changes in their mood states and autonomic nervous, endocrine, and immune activities when autobiographic memory was evoked in the participants by asking them to smell an odor(s) that was nostalgic to them. The autobiographic memories associated with positive emotion resulted in increased positive mood states, such as comfort and happiness, and decreased negative mood states, such as anxiety. Furthermore, heart rate was decreased, skin-conductance level was increased, and peripheral interleukin-2 level was decreased after smelling the nostalgic odor. These psychological and physiological responses were significantly correlated. The present study suggests that odor-evoked autobiographic memory along with a positive feeling induce various physiological responses, including the autonomic nervous and immune activities. To the best of our knowledge, the present study is the first to observe an interaction between odor-evoked autobiographic memories and immune function.

  5. Evoked acoustic emission

    DEFF Research Database (Denmark)

    Elberling, C; Parbo, J; Johnsen, N J

    1985-01-01

    Stimulated acoustic emissions were recorded in response to tonal stimuli at 60 dB p.e. SPL in a small group of normal-hearing adults. Power spectral analysis reveals that the evoked activity from each ear contains energy in preferential frequency bands and the change of stimulus frequency has only...

  6. Pyk2 modulates hippocampal excitatory synapses and contributes to cognitive deficits in a Huntington’s disease model

    KAUST Repository

    Giralt, Albert; Brito, Veronica; Chevy, Quentin; Simonnet, Clé mence; Otsu, Yo; Cifuentes-Dí az, Carmen; Pins, Benoit de; Coura, Renata; Alberch, Jordi; Giné s, Sí lvia; Poncer, Jean-Christophe; Girault, Jean-Antoine

    2017-01-01

    The structure and function of spines and excitatory synapses are under the dynamic control of multiple signalling networks. Although tyrosine phosphorylation is involved, its regulation and importance are not well understood. Here we study the role of Pyk2, a non-receptor calcium-dependent protein-tyrosine kinase highly expressed in the hippocampus. Hippocampal-related learning and CA1 long-term potentiation are severely impaired in Pyk2-deficient mice and are associated with alterations in NMDA receptors, PSD-95 and dendritic spines. In cultured hippocampal neurons, Pyk2 has autophosphorylation-dependent and -independent roles in determining PSD-95 enrichment and spines density. Pyk2 levels are decreased in the hippocampus of individuals with Huntington and in the R6/1 mouse model of the disease. Normalizing Pyk2 levels in the hippocampus of R6/1 mice rescues memory deficits, spines pathology and PSD-95 localization. Our results reveal a role for Pyk2 in spine structure and synaptic function, and suggest that its deficit contributes to Huntington’s disease cognitive impairments.

  7. Pyk2 modulates hippocampal excitatory synapses and contributes to cognitive deficits in a Huntington’s disease model

    KAUST Repository

    Giralt, Albert

    2017-05-30

    The structure and function of spines and excitatory synapses are under the dynamic control of multiple signalling networks. Although tyrosine phosphorylation is involved, its regulation and importance are not well understood. Here we study the role of Pyk2, a non-receptor calcium-dependent protein-tyrosine kinase highly expressed in the hippocampus. Hippocampal-related learning and CA1 long-term potentiation are severely impaired in Pyk2-deficient mice and are associated with alterations in NMDA receptors, PSD-95 and dendritic spines. In cultured hippocampal neurons, Pyk2 has autophosphorylation-dependent and -independent roles in determining PSD-95 enrichment and spines density. Pyk2 levels are decreased in the hippocampus of individuals with Huntington and in the R6/1 mouse model of the disease. Normalizing Pyk2 levels in the hippocampus of R6/1 mice rescues memory deficits, spines pathology and PSD-95 localization. Our results reveal a role for Pyk2 in spine structure and synaptic function, and suggest that its deficit contributes to Huntington’s disease cognitive impairments.

  8. Stress-restress evokes sustained iNOS activity and altered GABA levels and NMDA receptors in rat hippocampus

    DEFF Research Database (Denmark)

    Harvey, Brian H; Oosthuizen, Frasia; Brand, Linda

    2004-01-01

    . The NOS isoform involved, and the role of stress-mediated corticosterone release in NOS activation, was verified with the administration of selective iNOS and nNOS inhibitors, aminoguanidine (50 mg/kg/day i.p.) and 7-nitroindazole (12.5 mg/kg/day i.p.), and the steroid synthesis inhibitor, ketoconazole...... (24 mg/kg/day i.p.), administered for 21 days prior to and during the stress procedure. RESULTS: Stress evoked a sustained increase in NOS activity, but reduced NMDA receptor density and total GABA levels. Aminoguanidine or ketoconazole, but not 7-nitroindazole or saline, blocked stress-induced NOS...

  9. Altered inhibition in Tuberous Sclerosis and Type IIb cortical dysplasia

    Science.gov (United States)

    Talos, Delia M.; Sun, Hongyu; Kosaras, Bela; Joseph, Annelise; Folkerth, Rebecca D.; Poduri, Annapurna; Madsen, Joseph R.; Black, Peter M.; Jensen, Frances E.

    2012-01-01

    Objective The most common neurological symptom of tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) is early-life refractory epilepsy. As previous studies have shown enhanced excitatory glutamatergic neurotransmission in TSC and FCD brains, we hypothesized that neurons associated with these lesions may also express altered GABAA receptor (GABAAR)-mediated inhibition. Methods Expression of the GABAAR subunitsα1 and α4, the Na+-K+-2Cl− (NKCC1), and the K+−Cl− (KCC2) transporters in human TSC and FCD Type II specimens were analyzed by Western blot and double label immunocytochemistry. GABAAR responses in dysplastic neurons from a single case of TSC were measured by perforated-patch recording and compared to normal-appearing cortical neurons from a non-TSC epilepsy case. Results TSC and FCD Type IIb lesions demonstrated decreased expression of the GABAAR α1, increased NKCC1 and decreased KCC2 levels. In contrast, FCD Type IIa lesions showed decreased α4, and increased expression of both NKCC1 and KCC2 transporters. Patch clamp recordings from dysplastic neurons in acute slices from TSC tubers demonstrated excitatory GABAAR responses that were significantly attenuated by the NKCC1 inhibitor bumetanide, in contrast to hyperpolarizing GABAAR-mediated currents in normal neurons from non-TSC cortical slices. Interpretation Expression and function of GABAARs in TSC and FCD IIb suggests the relative benzodiazepine insensitivity and more excitatory action of GABA compared to FCD IIa. These factors may contribute to resistance of seizure activity to anticonvulsants that increase GABAergic function, and may justify add-on trials of the NKCC1 inhibitor bumetanide for the treatment of TSC and FCD Type IIb related epilepsy. PMID:22447678

  10. Acute stress increases depolarization-evoked glutamate release in the rat prefrontal/frontal cortex: the dampening action of antidepressants.

    Directory of Open Access Journals (Sweden)

    Laura Musazzi

    2010-01-01

    Full Text Available Behavioral stress is recognized as a main risk factor for neuropsychiatric diseases. Converging evidence suggested that acute stress is associated with increase of excitatory transmission in certain forebrain areas. Aim of this work was to investigate the mechanism whereby acute stress increases glutamate release, and if therapeutic drugs prevent the effect of stress on glutamate release.Rats were chronically treated with vehicle or drugs employed for therapy of mood/anxiety disorders (fluoxetine, desipramine, venlafaxine, agomelatine and then subjected to unpredictable footshock stress. Acute stress induced marked increase in depolarization-evoked release of glutamate from synaptosomes of prefrontal/frontal cortex in superfusion, and the chronic drug treatments prevented the increase of glutamate release. Stress induced rapid increase in the circulating levels of corticosterone in all rats (both vehicle- and drug-treated, and glutamate release increase was blocked by previous administration of selective antagonist of glucocorticoid receptor (RU 486. On the molecular level, stress induced accumulation of presynaptic SNARE complexes in synaptic membranes (both in vehicle- and drug-treated rats. Patch-clamp recordings of pyramidal neurons in the prefrontal cortex revealed that stress increased glutamatergic transmission through both pre- and postsynaptic mechanisms, and that antidepressants may normalize it by reducing release probability.Acute footshock stress up-regulated depolarization-evoked release of glutamate from synaptosomes of prefrontal/frontal cortex. Stress-induced increase of glutamate release was dependent on stimulation of glucocorticoid receptor by corticosterone. Because all drugs employed did not block either elevation of corticosterone or accumulation of SNARE complexes, the dampening action of the drugs on glutamate release must be downstream of these processes. This novel effect of antidepressants on the response to stress

  11. Excitatory Synaptic Drive and Feedforward Inhibition in the Hippocampal CA3 Circuit Are Regulated by SynCAM 1.

    Science.gov (United States)

    Park, Kellie A; Ribic, Adema; Laage Gaupp, Fabian M; Coman, Daniel; Huang, Yuegao; Dulla, Chris G; Hyder, Fahmeed; Biederer, Thomas

    2016-07-13

    Select adhesion proteins control the development of synapses and modulate their structural and functional properties. Despite these important roles, the extent to which different synapse-organizing mechanisms act across brain regions to establish connectivity and regulate network properties is incompletely understood. Further, their functional roles in different neuronal populations remain to be defined. Here, we applied diffusion tensor imaging (DTI), a modality of magnetic resonance imaging (MRI), to map connectivity changes in knock-out (KO) mice lacking the synaptogenic cell adhesion protein SynCAM 1. This identified reduced fractional anisotropy in the hippocampal CA3 area in absence of SynCAM 1. In agreement, mossy fiber refinement in CA3 was impaired in SynCAM 1 KO mice. Mossy fibers make excitatory inputs onto postsynaptic specializations of CA3 pyramidal neurons termed thorny excrescences and these structures were smaller in the absence of SynCAM 1. However, the most prevalent targets of mossy fibers are GABAergic interneurons and SynCAM 1 loss unexpectedly reduced the number of excitatory terminals onto parvalbumin (PV)-positive interneurons in CA3. SynCAM 1 KO mice additionally exhibited lower postsynaptic GluA1 expression in these PV-positive interneurons. These synaptic imbalances in SynCAM 1 KO mice resulted in CA3 disinhibition, in agreement with reduced feedforward inhibition in this network in the absence of SynCAM 1-dependent excitatory drive onto interneurons. In turn, mice lacking SynCAM 1 were impaired in memory tasks involving CA3. Our results support that SynCAM 1 modulates excitatory mossy fiber inputs onto both interneurons and principal neurons in the hippocampal CA3 area to balance network excitability. This study advances our understanding of synapse-organizing mechanisms on two levels. First, the data support that synaptogenic proteins guide connectivity and can function in distinct brain regions even if they are expressed broadly

  12. Activation of serotonin 2A receptors underlies the psilocybin-induced effects on α oscillations, N170 visual-evoked potentials, and visual hallucinations.

    Science.gov (United States)

    Kometer, Michael; Schmidt, André; Jäncke, Lutz; Vollenweider, Franz X

    2013-06-19

    Visual illusions and hallucinations are hallmarks of serotonergic hallucinogen-induced altered states of consciousness. Although the serotonergic hallucinogen psilocybin activates multiple serotonin (5-HT) receptors, recent evidence suggests that activation of 5-HT2A receptors may lead to the formation of visual hallucinations by increasing cortical excitability and altering visual-evoked cortical responses. To address this hypothesis, we assessed the effects of psilocybin (215 μg/kg vs placebo) on both α oscillations that regulate cortical excitability and early visual-evoked P1 and N170 potentials in healthy human subjects. To further disentangle the specific contributions of 5-HT2A receptors, subjects were additionally pretreated with the preferential 5-HT2A receptor antagonist ketanserin (50 mg vs placebo). We found that psilocybin strongly decreased prestimulus parieto-occipital α power values, thus precluding a subsequent stimulus-induced α power decrease. Furthermore, psilocybin strongly decreased N170 potentials associated with the appearance of visual perceptual alterations, including visual hallucinations. All of these effects were blocked by pretreatment with the 5-HT2A antagonist ketanserin, indicating that activation of 5-HT2A receptors by psilocybin profoundly modulates the neurophysiological and phenomenological indices of visual processing. Specifically, activation of 5-HT2A receptors may induce a processing mode in which stimulus-driven cortical excitation is overwhelmed by spontaneous neuronal excitation through the modulation of α oscillations. Furthermore, the observed reduction of N170 visual-evoked potentials may be a key mechanism underlying 5-HT2A receptor-mediated visual hallucinations. This change in N170 potentials may be important not only for psilocybin-induced states but also for understanding acute hallucinatory states seen in psychiatric disorders, such as schizophrenia and Parkinson's disease.

  13. Calcium-dependent smooth muscle excitatory effect elicited by the venom of the hydrocoral Millepora complanata.

    Science.gov (United States)

    Rojas, Alejandra; Torres, Mónica; Rojas, J Isela; Feregrino, Angélica; Heimer-de la Cotera, Edgar P

    2002-06-01

    In the present paper, we describe the results obtained from a preliminary pharmacological and biochemical study of the fire coral Millepora complanata, a regular component of coral reefs in the Mexican Caribbean. The protein-containing crude extract obtained from M. complanata (tested from 0.001 to 1000 microg protein/ml) caused a concentration-dependent stimulation of spontaneous contractions of the guinea pig ileum. The extract (EC(50)=11.55+/-2.36 microg/ml) was approximately 12-fold less potent than ionomycin (EC(50)=0.876+/-0.25 microg/ml) and its maximum induced contraction (1mg protein/ml) was equivalent to 68% of the response to 60mM KCl. FPLC size exclusion chromatography of the M. complanta extract afforded 12 primary fractions, of which only FV (containing proteins with molecular weights ranging from 17 to 44 kDa) and FVIII (consisting of peptides with molecular weights lesser than 1.8k Da) elicited an excitatory effect when tested at the EC(50) of the original extract. After incubation in Ca(2+)-free medium, the ileal response to FV and FVIII was significantly reduced. Blockage of L-type Ca(2+) channels with nifedipine (1 microM) inhibited FV and FVIII-evoked contractions. Cd(2+) (10 microM), an unspecific blocker of voltage-activated calcium channels, also antagonized FV and FVIII-induced effects, whereas the Na(+) channel blocker tetrodotoxin (10nM) did not significantly affect FV and FVIII responses. These results suggest that the contractions induced by the bioactive fractions obtained from the crude extract of M. complanata are caused mainly by a direct action on smooth muscle cells, via an increase in Ca(2+) permeability that occurs, at least partly, through L-type voltage-dependent Ca(2+) channels found in the cell membrane of smooth muscle. Copright 2002 Elsevier Science Ltd.

  14. Brainstem evoked potentials in infantile spasms

    International Nuclear Information System (INIS)

    Miyazaki, Masahito; Hashimoto, Toshiaki; Murakawa, Kazuyoshi; Tayama, Masanobu; Kuroda, Yasuhiro

    1992-01-01

    In ten patients with infantile spasms, brainstem evoked potentials and MRI examinations were performed to evaluate the brainstem involvement. The result of short latency somatosensory evoked potentials (SSEP) following the right median nerve stimulation revealed abnormal findings including the absence or low amplitudes of the waves below wave P3 and delayed central conduction time in 7 of the ten patients. The result of auditory brainstem responses (ABR) revealed abnormal findings including low amplitudes of wave V, prolonged interpeak latency of waves I-V and absence of the waves below wave IV in 5 of the ten patients. The result of the MRI examinations revealed various degrees of the brainstem atrophy in 6 of the ten patients, all of whom showed abnormal brainstem evoked potentials. The result of this study demonstrates that patients with infantile spasms are frequently associated with brainstem dysfunction and raises the possibility that brainstem atrophy might be a cause of infantile spasms. (author)

  15. Measurement of insulin and C-peptide excitatory test levels in gestational diabetes mellitus

    International Nuclear Information System (INIS)

    Du Tongxin; Wang Zizheng

    2001-01-01

    To investigate the function of islet β cells in patients with gestational diabetes mellitus (GDM), serum insulin and C-peptide (C-P) excitatory test levels were measured dynamically by radioimmunoassay in 41 patients with GDM and 30 normal pregnant controls. The results showed that there were significant difference in insulin and C-peptide excitatory test levels between normal pregnancy for 32-40 weeks and patients with GDM (P < 0.001). The secretory peak of insulin occurred at 60 min in normal pregnancy, while at 120 min in patients with GDM, and the recovery postponed in patients with GDM. The peak time for C-P was just as same as that of insulin, but the peak error for C-P between normal pregnant controls and patients with GDM was more larger than that for insulin and it recovered more slowly. It suggested that majority of islet β cells in patients with GDM were good enough for response to islet resistance factors and big stress from pregnancy, and also suggested a relation between pregnancy and islet β cells function

  16. New players tip the scales in the balance between excitatory and inhibitory synapses

    Directory of Open Access Journals (Sweden)

    El-Husseini Alaa

    2005-03-01

    Full Text Available Abstract Synaptogenesis is a highly controlled process, involving a vast array of players which include cell adhesion molecules, scaffolding and signaling proteins, neurotransmitter receptors and proteins associated with the synaptic vesicle machinery. These molecules cooperate in an intricate manner on both the pre- and postsynaptic sides to orchestrate the precise assembly of neuronal contacts. This is an amazing feat considering that a single neuron receives tens of thousands of synaptic inputs but virtually no mismatch between pre- and postsynaptic components occur in vivo. One crucial aspect of synapse formation is whether a nascent synapse will develop into an excitatory or inhibitory contact. The tight control of a balance between the types of synapses formed regulates the overall neuronal excitability, and is thus critical for normal brain function and plasticity. However, little is known about how this balance is achieved. This review discusses recent findings which provide clues to how neurons may control excitatory and inhibitory synapse formation, with focus on the involvement of the neuroligin family and PSD-95 in this process.

  17. A Role for Excitatory Amino Acids in Diabetic Eye Disease

    Directory of Open Access Journals (Sweden)

    Jose E. Pulido

    2007-01-01

    Full Text Available Diabetic retinopathy is a leading cause of vision loss. The primary clinical hallmarks are vascular changes that appear to contribute to the loss of sight. In a number of neurodegenerative disorders there is an appreciation that increased levels of excitatory amino acids are excitotoxic. The primary amino acid responsible appears to be the neurotransmitter glutamate. This review examines the nature of glutamatergic signaling at the retina and the growing evidence from clinical and animal model studies that glutamate may be playing similar excitotoxic roles at the diabetic retina.

  18. Can visual evoked potentials be used in biometric identification?

    Science.gov (United States)

    Power, Alan J; Lalor, Edmund C; Reilly, Richard B

    2006-01-01

    Due to known differences in the anatomical structure of the visual pathways and generators in different individuals, the use of visual evoked potentials offers the possibility of an alternative to existing biometrics methods. A study based on visual evoked potentials from 13 individuals was carried out to assess the best combination of temporal, spectral and AR modeling features to realize a robust biometric. From the results it can be concluded that visual evoked potentials show considerable biometric qualities, with classification accuracies reaching a high of 86.54% and that a specific temporal and spectral combination was found to be optimal. Based on these results the visual evoked potential may be a useful tool in biometric identification when used in conjunction with more established biometric methods.

  19. Enhanced NMDA receptor-mediated intracellular calcium signaling in magnocellular neurosecretory neurons in heart failure rats.

    Science.gov (United States)

    Stern, Javier E; Potapenko, Evgeniy S

    2013-08-15

    An enhanced glutamate excitatory function within the hypothalamic supraoptic and paraventricluar nuclei is known to contribute to increased neurosecretory and presympathetic neuronal activity, and hence, neurohumoral activation, during heart failure (HF). Still, the precise mechanisms underlying enhanced glutamate-driven neuronal activity in HF remain to be elucidated. Here, we performed simultaneous electrophysiology and fast confocal Ca²⁺ imaging to determine whether altered N-methyl-d-aspartate (NMDA) receptor-mediated changes in intracellular Ca²⁺ levels (NMDA-ΔCa²⁺) occurred in hypothalamic magnocellular neurosecretory cells (MNCs) in HF rats. We found that activation of NMDA receptors resulted in a larger ΔCa²⁺ in MNCs from HF when compared with sham rats. The enhanced NMDA-ΔCa²⁺ was neither dependent on the magnitude of the NMDA-mediated current (voltage clamp) nor on the degree of membrane depolarization or firing activity evoked by NMDA (current clamp). Differently from NMDA receptor activation, firing activity evoked by direct membrane depolarization resulted in similar changes in intracellular Ca²⁺ in sham and HF rats. Taken together, our results support a relatively selective alteration of intracellular Ca²⁺ homeostasis and signaling following activation of NMDA receptors in MNCs during HF. The downstream functional consequences of such altered ΔCa²⁺ signaling during HF are discussed.

  20. Age-related deficits in synaptic plasticity rescued by activating PKA or PKC in sensory neurons of Aplysia californica

    Directory of Open Access Journals (Sweden)

    Andrew T Kempsell

    2015-09-01

    Full Text Available Brain aging is associated with declines in synaptic function that contribute to memory loss, including reduced postsynaptic response to neurotransmitters and decreased neuronal excitability. To understand how aging affects memory in a simple neural circuit, we studied neuronal proxies of memory for sensitization in mature versus advanced age Aplysia. Glutamate- (L-Glu- evoked excitatory currents were facilitated by the neuromodulator serotonin (5-HT in sensory neurons (SN isolated from mature but not aged animals. Activation of PKA and PKC signaling rescued facilitation of L-Glu currents in aged SN. Similarly, PKA and PKC activators restored increased excitability in aged tail SN. These results suggest that altered synaptic plasticity during aging involves defects in second messenger systems

  1. Binaural interaction in auditory evoked potentials: Brainstem, middle- and long-latency components

    OpenAIRE

    McPherson, DL; Starr, A

    1993-01-01

    Binaural interaction occurs in the auditory evoked potentials when the sum of the monaural auditory evoked potentials are not equivalent to the binaural evoked auditory potentials. Binaural interaction of the early- (0-10 ms), middle- (10-50 ms) and long-latency (50-200 ms) auditory evoked potentials was studied in 17 normal young adults. For the early components, binaural interaction was maximal at 7.35 ms accounting for a reduction of 21% of the amplitude of the binaural evoked potentials. ...

  2. Effects of excitatory and inhibitory neurotransmission on motor patterns of human sigmoid colon in vitro

    Science.gov (United States)

    Aulí, M; Martínez, E; Gallego, D; Opazo, A; Espín, F; Martí-Gallostra, M; Jiménez, M; Clavé, P

    2008-01-01

    Background and purpose: To characterize the in vitro motor patterns and the neurotransmitters released by enteric motor neurons (EMNs) in the human sigmoid colon. Experimental approach: Sigmoid circular strips were studied in organ baths. EMNs were stimulated by electrical field stimulation (EFS) and through nicotinic ACh receptors. Key results: Strips developed weak spontaneous rhythmic contractions (3.67±0.49 g, 2.54±0.15 min) unaffected by the neurotoxin tetrodotoxin (TTX; 1 μM). EFS induced strong contractions during (on, 56%) or after electrical stimulus (off, 44%), both abolished by TTX. Nicotine (1–100 μM) inhibited spontaneous contractions. Latency of off-contractions and nicotine responses were reduced by NG-nitro-L-arginine (1 mM) and blocked after further addition of apamin (1 μM) or the P2Y1 receptor antagonist MRS 2179 (10 μM) and were unaffected by the P2X antagonist NF279 (10 μM) or α-chymotrypsin (10 U mL−1). Amplitude of on- and off-contractions was reduced by atropine (1 μM) and the selective NK2 receptor antagonist Bz-Ala-Ala-D-Trp-Phe-D-Pro-Pro-Nle-NH2 (1 μM). MRS 2179 reduced the amplitude of EFS on- and off-contractions without altering direct muscular contractions induced by ACh (1 nM–1 mM) or substance P (1 nM–10 μM). Conclusions and implications: Latency of EFS-induced off-contractions and inhibition of spontaneous motility by nicotine are caused by stimulation of inhibitory EMNs coreleasing NO and a purine acting at muscular P2Y1 receptors through apamin-sensitive K+ channels. EFS-induced on- and off-contractions are caused by stimulation of excitatory EMNs coreleasing ACh and tachykinins acting on muscular muscarinic and NK2 receptors. Prejunctional P2Y1 receptors might modulate the activity of excitatory EMNs. P2Y1 and NK2 receptors might be therapeutic targets for colonic motor disorders. PMID:18846038

  3. Hierarchical clustering of gene expression patterns in the Eomes + lineage of excitatory neurons during early neocortical development

    Directory of Open Access Journals (Sweden)

    Cameron David A

    2012-08-01

    Full Text Available Abstract Background Cortical neurons display dynamic patterns of gene expression during the coincident processes of differentiation and migration through the developing cerebrum. To identify genes selectively expressed by the Eomes + (Tbr2 lineage of excitatory cortical neurons, GFP-expressing cells from Tg(Eomes::eGFP Gsat embryos were isolated to > 99% purity and profiled. Results We report the identification, validation and spatial grouping of genes selectively expressed within the Eomes + cortical excitatory neuron lineage during early cortical development. In these neurons 475 genes were expressed ≥ 3-fold, and 534 genes ≤ 3-fold, compared to the reference population of neuronal precursors. Of the up-regulated genes, 328 were represented at the Genepaint in situ hybridization database and 317 (97% were validated as having spatial expression patterns consistent with the lineage of differentiating excitatory neurons. A novel approach for quantifying in situ hybridization patterns (QISP across the cerebral wall was developed that allowed the hierarchical clustering of genes into putative co-regulated groups. Forty four candidate genes were identified that show spatial expression with Intermediate Precursor Cells, 49 candidate genes show spatial expression with Multipolar Neurons, while the remaining 224 genes achieved peak expression in the developing cortical plate. Conclusions This analysis of differentiating excitatory neurons revealed the expression patterns of 37 transcription factors, many chemotropic signaling molecules (including the Semaphorin, Netrin and Slit signaling pathways, and unexpected evidence for non-canonical neurotransmitter signaling and changes in mechanisms of glucose metabolism. Over half of the 317 identified genes are associated with neuronal disease making these findings a valuable resource for studies of neurological development and disease.

  4. Integrated plasticity at inhibitory and excitatory synapses in the cerebellar circuit

    Directory of Open Access Journals (Sweden)

    Lisa eMapelli

    2015-05-01

    Full Text Available The way long-term potentiation (LTP and depression (LTD are integrated within the different synapses of brain neuronal circuits is poorly understood. In order to progress beyond the identification of specific molecular mechanisms, a system in which multiple forms of plasticity can be correlated with large-scale neural processing is required. In this paper we take as an example the cerebellar network , in which extensive investigations have revealed LTP and LTD at several excitatory and inhibitory synapses. Cerebellar LTP and LTD occur in all three main cerebellar subcircuits (granular layer, molecular layer, deep cerebellar nuclei and correspondingly regulate the function of their three main neurons: granule cells (GrCs, Purkinje cells (PCs and deep cerebellar nuclear (DCN cells. All these neurons, in addition to be excited, are reached by feed-forward and feed-back inhibitory connections, in which LTP and LTD may either operate synergistically or homeostatically in order to control information flow through the circuit. Although the investigation of individual synaptic plasticities in vitro is essential to prove their existence and mechanisms, it is insufficient to generate a coherent view of their impact on network functioning in vivo. Recent computational models and cell-specific genetic mutations in mice are shedding light on how plasticity at multiple excitatory and inhibitory synapses might regulate neuronal activities in the cerebellar circuit and contribute to learning and memory and behavioral control.

  5. Integrated plasticity at inhibitory and excitatory synapses in the cerebellar circuit.

    Science.gov (United States)

    Mapelli, Lisa; Pagani, Martina; Garrido, Jesus A; D'Angelo, Egidio

    2015-01-01

    The way long-term potentiation (LTP) and depression (LTD) are integrated within the different synapses of brain neuronal circuits is poorly understood. In order to progress beyond the identification of specific molecular mechanisms, a system in which multiple forms of plasticity can be correlated with large-scale neural processing is required. In this paper we take as an example the cerebellar network, in which extensive investigations have revealed LTP and LTD at several excitatory and inhibitory synapses. Cerebellar LTP and LTD occur in all three main cerebellar subcircuits (granular layer, molecular layer, deep cerebellar nuclei) and correspondingly regulate the function of their three main neurons: granule cells (GrCs), Purkinje cells (PCs) and deep cerebellar nuclear (DCN) cells. All these neurons, in addition to be excited, are reached by feed-forward and feed-back inhibitory connections, in which LTP and LTD may either operate synergistically or homeostatically in order to control information flow through the circuit. Although the investigation of individual synaptic plasticities in vitro is essential to prove their existence and mechanisms, it is insufficient to generate a coherent view of their impact on network functioning in vivo. Recent computational models and cell-specific genetic mutations in mice are shedding light on how plasticity at multiple excitatory and inhibitory synapses might regulate neuronal activities in the cerebellar circuit and contribute to learning and memory and behavioral control.

  6. Voluntary nicotine consumption triggers in vivo potentiation of cortical excitatory drives to midbrain dopaminergic neurons

    NARCIS (Netherlands)

    Caillé, S.; Guillem, K.; Cador, M.; Manzoni, O.; Georges, F.

    2009-01-01

    Active response to either natural or pharmacological reward causes synaptic modifications to excitatory synapses on dopamine (DA) neurons of the ventral tegmental area (VTA). Here, we examine these modifications using nicotine, the main addictive component of tobacco, which is a potent regulator of

  7. Excitatory and inhibitory pathways modulate kainate excitotoxicity in hippocampal slice cultures

    DEFF Research Database (Denmark)

    Casaccia-Bonnefil, P; Benedikz, Eirikur; Rai, R

    1993-01-01

    In organotypic hippocampal slice cultures, kainate (KA) specifically induces cell loss in the CA3 region while N-methyl-D-aspartate induces cell loss in the CA1 region. The sensitivity of slice cultures to KA toxicity appears only after 2 weeks in vitro which parallels the appearance of mossy...... fibers. KA toxicity is potentiated by co-application with the GABA-A antagonist, picrotoxin. These data suggest that the excitotoxicity of KA in slice cultures is modulated by both excitatory and inhibitory synapses....

  8. Enhanced excitatory input to melanin concentrating hormone neurons during developmental period of high food intake is mediated by GABA.

    Science.gov (United States)

    Li, Ying; van den Pol, Anthony N

    2009-12-02

    In contrast to the local axons of GABA neurons of the cortex and hippocampus, lateral hypothalamic neurons containing melanin concentrating hormone (MCH) and GABA send long axons throughout the brain and play key roles in energy homeostasis and mental status. In adults, MCH neurons maintain a hyperpolarized membrane potential and most of the synaptic input is inhibitory. In contrast, we found that developing MCH neurons received substantially more excitatory synaptic input. Based on gramicidin-perforated patch recordings in hypothalamic slices from MCH-green fluorescent protein transgenic mice, we found that GABA was the primary excitatory synaptic transmitter in embryonic and neonatal ages up to postnatal day 10. Surprisingly, glutamate assumed only a minor excitatory role, if any. GABA plays a complex role in developing MCH neurons, with its actions conditionally dependent on a number of factors. GABA depolarization could lead to an increase in spikes either independently or in summation with other depolarizing stimuli, or alternately, depending on the relative timing of other depolarizing events, could lead to shunting inhibition. The developmental shift from depolarizing to hyperpolarizing occurred later in the dendrites than in the cell body. Early GABA depolarization was based on a Cl(-)-dependent inward current. An interesting secondary depolarization in mature neurons that followed an initial hyperpolarization was based on a bicarbonate mechanism. Thus during the early developmental period when food consumption is high, MCH neurons are more depolarized than in the adult, and an increased level of excitatory synaptic input to these orexigenic cells is mediated by GABA.

  9. Excitatory inputs to four types of spinocerebellar tract neurons in the cat and the rat thoraco-lumbar spinal cord

    Science.gov (United States)

    Shrestha, Sony Shakya; Bannatyne, B Anne; Jankowska, Elzbieta; Hammar, Ingela; Nilsson, Elin; Maxwell, David J

    2012-01-01

    The cerebellum receives information from the hindlimbs through several populations of spinocerebellar tract neurons. Although the role of these neurons has been established in electrophysiological experiments, the relative contribution of afferent fibres and central neurons to their excitatory input has only been estimated approximately so far. Taking advantage of differences in the immunohistochemistry of glutamatergic terminals of peripheral afferents and of central neurons (with vesicular glutamate transporters VGLUT1 or VGLUT2, respectively), we compared sources of excitatory input to four populations of spinocerebellar neurons in the thoraco-lumbar spinal cord: dorsal spinocerebellar tract neurons located in Clarke's column (ccDSCT) and in the dorsal horn (dhDSCT) and ventral spinocerebellar tract (VSCT) neurons including spinal border (SB) neurons. This was done on 22 electrophysiologically identified intracellularly labelled neurons in cats and on 80 neurons labelled by retrograde transport of cholera toxin b subunit injected into the cerebellum of rats. In both species distribution of antibodies against VGLUT1 and VGLUT2 on SB neurons (which have dominating inhibitory input from limb muscles), revealed very few VGLUT1 contacts and remarkably high numbers of VGLUT2 contacts. In VSCT neurons with excitatory afferent input, the number of VGLUT1 contacts was relatively high although VGLUT2 contacts likewise dominated, while the proportions of VGLUT1 and VGLUT2 immunoreactive terminals were the reverse on the two populations of DSCT neurons. These findings provide morphological evidence that SB neurons principally receive excitatory inputs from central neurons and provide the cerebellum with information regarding central neuronal activity. PMID:22371473

  10. Slow cortical evoked potentials after noise exposure

    Energy Technology Data Exchange (ETDEWEB)

    von Wedel, H; Opitz, H J

    1979-07-01

    Human cortical evoked potentials under conditions of stimuation are registrated in the post-stimulatory phase of a five minutes lasting equally masking white noise (90 dB HL). Changes of the evoked potentials during adaptation, possible analogy with high tone losses after noise representation and the origin of tinnitus are examined. Stimulation was started 3 sec after the off-effect of the noise. For five minutes periodically tone bursts were represented. Each train of stimulation consists of tone bursts of three frequencies: 2 kcs, 4 kcs, 8 kcs. The 0.5 sec lasting tones were separated by pauses of 2 sec. During the experiment stimulation and analysis were controlled by a computer. Changes in latency and amplitudes of the cortical evoked potentials were registered. Changes of the adaptation patterns as a function of the poststimulatory time are discussed.

  11. The Paradox of Music-Evoked Sadness: An Online Survey

    Science.gov (United States)

    Taruffi, Liila; Koelsch, Stefan

    2014-01-01

    This study explores listeners’ experience of music-evoked sadness. Sadness is typically assumed to be undesirable and is therefore usually avoided in everyday life. Yet the question remains: Why do people seek and appreciate sadness in music? We present findings from an online survey with both Western and Eastern participants (N = 772). The survey investigates the rewarding aspects of music-evoked sadness, as well as the relative contribution of listener characteristics and situational factors to the appreciation of sad music. The survey also examines the different principles through which sadness is evoked by music, and their interaction with personality traits. Results show 4 different rewards of music-evoked sadness: reward of imagination, emotion regulation, empathy, and no “real-life” implications. Moreover, appreciation of sad music follows a mood-congruent fashion and is greater among individuals with high empathy and low emotional stability. Surprisingly, nostalgia rather than sadness is the most frequent emotion evoked by sad music. Correspondingly, memory was rated as the most important principle through which sadness is evoked. Finally, the trait empathy contributes to the evocation of sadness via contagion, appraisal, and by engaging social functions. The present findings indicate that emotional responses to sad music are multifaceted, are modulated by empathy, and are linked with a multidimensional experience of pleasure. These results were corroborated by a follow-up survey on happy music, which indicated differences between the emotional experiences resulting from listening to sad versus happy music. This is the first comprehensive survey of music-evoked sadness, revealing that listening to sad music can lead to beneficial emotional effects such as regulation of negative emotion and mood as well as consolation. Such beneficial emotional effects constitute the prime motivations for engaging with sad music in everyday life. PMID:25330315

  12. The paradox of music-evoked sadness: an online survey.

    Directory of Open Access Journals (Sweden)

    Liila Taruffi

    Full Text Available This study explores listeners' experience of music-evoked sadness. Sadness is typically assumed to be undesirable and is therefore usually avoided in everyday life. Yet the question remains: Why do people seek and appreciate sadness in music? We present findings from an online survey with both Western and Eastern participants (N = 772. The survey investigates the rewarding aspects of music-evoked sadness, as well as the relative contribution of listener characteristics and situational factors to the appreciation of sad music. The survey also examines the different principles through which sadness is evoked by music, and their interaction with personality traits. Results show 4 different rewards of music-evoked sadness: reward of imagination, emotion regulation, empathy, and no "real-life" implications. Moreover, appreciation of sad music follows a mood-congruent fashion and is greater among individuals with high empathy and low emotional stability. Surprisingly, nostalgia rather than sadness is the most frequent emotion evoked by sad music. Correspondingly, memory was rated as the most important principle through which sadness is evoked. Finally, the trait empathy contributes to the evocation of sadness via contagion, appraisal, and by engaging social functions. The present findings indicate that emotional responses to sad music are multifaceted, are modulated by empathy, and are linked with a multidimensional experience of pleasure. These results were corroborated by a follow-up survey on happy music, which indicated differences between the emotional experiences resulting from listening to sad versus happy music. This is the first comprehensive survey of music-evoked sadness, revealing that listening to sad music can lead to beneficial emotional effects such as regulation of negative emotion and mood as well as consolation. Such beneficial emotional effects constitute the prime motivations for engaging with sad music in everyday life.

  13. The paradox of music-evoked sadness: an online survey.

    Science.gov (United States)

    Taruffi, Liila; Koelsch, Stefan

    2014-01-01

    This study explores listeners' experience of music-evoked sadness. Sadness is typically assumed to be undesirable and is therefore usually avoided in everyday life. Yet the question remains: Why do people seek and appreciate sadness in music? We present findings from an online survey with both Western and Eastern participants (N = 772). The survey investigates the rewarding aspects of music-evoked sadness, as well as the relative contribution of listener characteristics and situational factors to the appreciation of sad music. The survey also examines the different principles through which sadness is evoked by music, and their interaction with personality traits. Results show 4 different rewards of music-evoked sadness: reward of imagination, emotion regulation, empathy, and no "real-life" implications. Moreover, appreciation of sad music follows a mood-congruent fashion and is greater among individuals with high empathy and low emotional stability. Surprisingly, nostalgia rather than sadness is the most frequent emotion evoked by sad music. Correspondingly, memory was rated as the most important principle through which sadness is evoked. Finally, the trait empathy contributes to the evocation of sadness via contagion, appraisal, and by engaging social functions. The present findings indicate that emotional responses to sad music are multifaceted, are modulated by empathy, and are linked with a multidimensional experience of pleasure. These results were corroborated by a follow-up survey on happy music, which indicated differences between the emotional experiences resulting from listening to sad versus happy music. This is the first comprehensive survey of music-evoked sadness, revealing that listening to sad music can lead to beneficial emotional effects such as regulation of negative emotion and mood as well as consolation. Such beneficial emotional effects constitute the prime motivations for engaging with sad music in everyday life.

  14. Genetic influence demonstrated for MEG-recorded somatosensory evoked responses

    NARCIS (Netherlands)

    van 't Ent, D.; van Soelen, I.L.C.; Stam, K.J.; de Geus, E.J.C.; Boomsma, D.I.

    2010-01-01

    We tested for a genetic influence on magnetoencephalogram (MEG)-recorded somatosensory evoked fields (SEFs) in 20 monozygotic (MZ) and 14 dizygotic (DZ) twin pairs. Previous electroencephalogram (EEG) studies that demonstrated a genetic contribution to evoked responses generally focused on

  15. Molecular components and functions of the endocannabinoid system in mouse prefrontal cortex.

    Directory of Open Access Journals (Sweden)

    Mathieu Lafourcade

    2007-08-01

    Full Text Available Cannabinoids have deleterious effects on prefrontal cortex (PFC-mediated functions and multiple evidences link the endogenous cannabinoid (endocannabinoid system, cannabis use and schizophrenia, a disease in which PFC functions are altered. Nonetheless, the molecular composition and the physiological functions of the endocannabinoid system in the PFC are unknown.Here, using electron microscopy we found that key proteins involved in endocannabinoid signaling are expressed in layers v/vi of the mouse prelimbic area of the PFC: presynaptic cannabinoid CB1 receptors (CB1R faced postsynaptic mGluR5 while diacylglycerol lipase alpha (DGL-alpha, the enzyme generating the endocannabinoid 2-arachidonoyl-glycerol (2-AG was expressed in the same dendritic processes as mGluR5. Activation of presynaptic CB1R strongly inhibited evoked excitatory post-synaptic currents. Prolonged synaptic stimulation at 10Hz induced a profound long-term depression (LTD of layers V/VI excitatory inputs. The endocannabinoid -LTD was presynaptically expressed and depended on the activation of postsynaptic mGluR5, phospholipase C and a rise in postsynaptic Ca(2+ as predicted from the localization of the different components of the endocannabinoid system. Blocking the degradation of 2-AG (with URB 602 but not of anandamide (with URB 597 converted subthreshold tetanus to LTD-inducing ones. Moreover, inhibiting the synthesis of 2-AG with Tetrahydrolipstatin, blocked endocannabinoid-mediated LTD. All together, our data show that 2-AG mediates LTD at these synapses.Our data show that the endocannabinoid -retrograde signaling plays a prominent role in long-term synaptic plasticity at the excitatory synapses of the PFC. Alterations of endocannabinoid -mediated synaptic plasticity may participate to the etiology of PFC-related pathologies.

  16. Visually Evoked Spiking Evolves While Spontaneous Ongoing Dynamics Persist

    DEFF Research Database (Denmark)

    Huys, Raoul; Jirsa, Viktor K; Darokhan, Ziauddin

    2016-01-01

    attractor. Its existence guarantees that evoked spiking return to the spontaneous state. However, the spontaneous ongoing spiking state and the visual evoked spiking states are qualitatively different and are separated by a threshold (separatrix). The functional advantage of this organization...

  17. The Duration of Motor Responses Evoked with Intracortical Microstimulation in Rats Is Primarily Modulated by Stimulus Amplitude and Train Duration.

    Directory of Open Access Journals (Sweden)

    Meghan Watson

    Full Text Available Microstimulation of brain tissue plays a key role in a variety of sensory prosthetics, clinical therapies and research applications, however the effects of stimulation parameters on the responses they evoke remain widely unknown. In particular, the effects of parameters when delivered in the form of a stimulus train as opposed to a single pulse are not well understood despite the prevalence of stimulus train use. We aimed to investigate the contribution of each parameter of a stimulus train to the duration of the motor responses they evoke in forelimb muscles. We used constant-current, biphasic, square wave pulse trains in acute terminal experiments under ketamine anaesthesia. Stimulation parameters were systematically tested in a pair-wise fashion in the caudal forelimb region of the motor cortex in 7 Sprague-Dawley rats while motor evoked potential (MEP recordings from the forelimb were used to quantify the influence of each parameter in the train. Stimulus amplitude and train duration were shown to be the dominant parameters responsible for increasing the total duration of the MEP, while interphase interval had no effect. Increasing stimulus frequency from 100-200 Hz or pulse duration from 0.18-0.34 ms were also effective methods of extending response durations. Response duration was strongly correlated with peak time and amplitude. Our findings suggest that motor cortex intracortical microstimulations are often conducted at a higher frequency rate and longer train duration than necessary to evoke maximal response duration. We demonstrated that the temporal properties of the evoked response can be both predicted by certain response metrics and modulated via alterations to the stimulation signal parameters.

  18. Slack KNa Channels Influence Dorsal Horn Synapses and Nociceptive Behavior.

    Science.gov (United States)

    Evely, Katherine M; Pryce, Kerri D; Bausch, Anne E; Lukowski, Robert; Ruth, Peter; Haj-Dahmane, Samir; Bhattacharjee, Arin

    2017-01-01

    The sodium-activated potassium channel Slack (Kcnt1, Slo2.2) is highly expressed in dorsal root ganglion neurons where it regulates neuronal firing. Several studies have implicated the Slack channel in pain processing, but the precise mechanism or the levels within the sensory pathway where channels are involved remain unclear. Here, we furthered the behavioral characterization of Slack channel knockout mice and for the first time examined the role of Slack channels in the superficial, pain-processing lamina of the dorsal horn. We performed whole-cell recordings from spinal cord slices to examine the intrinsic and synaptic properties of putative inhibitory and excitatory lamina II interneurons. Slack channel deletion altered intrinsic properties and synaptic drive to favor an overall enhanced excitatory tone. We measured the amplitudes and paired pulse ratio of paired excitatory post-synaptic currents at primary afferent synapses evoked by electrical stimulation of the dorsal root entry zone. We found a substantial decrease in the paired pulse ratio at synapses in Slack deleted neurons compared to wildtype, indicating increased presynaptic release from primary afferents. Corroborating these data, plantar test showed Slack knockout mice have an enhanced nociceptive responsiveness to localized thermal stimuli compared to wildtype mice. Our findings suggest that Slack channels regulate synaptic transmission within the spinal cord dorsal horn and by doing so establishes the threshold for thermal nociception.

  19. Enhanced quantal release of excitatory transmitter in anterior cingulate cortex of adult mice with chronic pain

    Directory of Open Access Journals (Sweden)

    Zhao Ming-Gao

    2009-01-01

    Full Text Available Abstract The anterior cingulate cortex (ACC is a forebrain structure that plays important roles in emotion, learning, memory and persistent pain. Our previous studies have demonstrated that the enhancement of excitatory synaptic transmission was induced by peripheral inflammation and nerve injury in ACC synapses. However, little information is available on their presynaptic mechanisms, since the source of the enhanced synaptic transmission could include the enhanced probability of neurotransmitter release at existing release sites and/or increases in the number of available vesicles. The present study aims to perform quantal analysis of excitatory synapses in the ACC with chronic pain to examine the source of these increases. The quantal analysis revealed that both probability of transmitter release and number of available vesicles were increased in a mouse model of peripheral inflammation, whereas only probability of transmitter release but not number of available vesicles was enhanced in a mouse model of neuropathic pain. In addition, we compared the miniature excitatory postsynaptic potentials (mEPSCs in ACC synapses with those in other pain-related brain areas such as the amygdala and spinal cord. Interestingly, the rate and amplitude of mEPSCs in ACC synapses were significantly lower than those in the amygdala and spinal cord. Our studies provide strong evidences that chronic inflammatory pain increases both probability of transmitter release and number of available vesicles, whereas neuropathic pain increases only probability of transmitter release in the ACC synapses.

  20. Joint angle affects volitional and magnetically-evoked neuromuscular performance differentially.

    Science.gov (United States)

    Minshull, C; Rees, D; Gleeson, N P

    2011-08-01

    This study examined the volitional and magnetically-evoked neuromuscular performance of the quadriceps femoris at functional knee joint angles adjacent to full extension. Indices of volitional and magnetically-evoked neuromuscular performance (N=15 healthy males, 23.5 ± 2.9 years, 71.5 ± 5.4 kg, 176.5 ± 5.5 cm) were obtained at 25°, 35° and 45° of knee flexion. Results showed that volitional and magnetically-evoked peak force (PF(V) and P(T)F(E), respectively) and electromechanical delay (EMD(V) and EMD(E), respectively) were enhanced by increased knee flexion. However, greater relative improvements in volitional compared to evoked indices of neuromuscular performance were observed with increasing flexion from 25° to 45° (e.g. EMD(V), EMD(E): 36% vs. 11% improvement, respectively; F([2,14])=6.8, pjoint positions. These findings suggest that the extent of the relative differential between volitional and evoked neuromuscular performance capabilities is joint angle-specific and not correlated with performance capabilities at adjacent angles, but tends to be smaller with increased flexion. As such, effective prediction of volitional from evoked performance capabilities at both analogous and adjacent knee joint positions would lack robustness. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. International Evoked Potentials Symposium

    CERN Document Server

    1980-01-01

    The past decade has seen great progress in the measurement of evoked potentials in man; a steady increase in our understanding of their charac­ teristics, their origins and their usefulness; and a growing application in the field of clinical diagnosis. The topic is a truly multidisciplinary one. Important research contributions have been made by workers of many different backgrounds and clinical applications span the specialities. This book represents a revised and updated version of the work originally presented at the international evoked potential symposium held in Nottingham 4-6 1978. The Nottingham Symposium provided a forum for a state-of-the-art discussion amongst workers from many different disciplines and from many different countries. For each major topic in the field an expert review set the scene for discussion of current research presentations. This format is retained in the book: the chapters in Part A provide the context in which the research presented in Part B is set. The task of selecting m...

  2. A Pixel-Encoder Retinal Ganglion Cell with Spatially Offset Excitatory and Inhibitory Receptive Fields

    Directory of Open Access Journals (Sweden)

    Keith P. Johnson

    2018-02-01

    Full Text Available The spike trains of retinal ganglion cells (RGCs are the only source of visual information to the brain. Here, we genetically identify an RGC type in mice that functions as a pixel encoder and increases firing to light increments (PixON-RGC. PixON-RGCs have medium-sized dendritic arbors and non-canonical center-surround receptive fields. From their receptive field center, PixON-RGCs receive only excitatory input, which encodes contrast and spatial information linearly. From their receptive field surround, PixON-RGCs receive only inhibitory input, which is temporally matched to the excitatory center input. As a result, the firing rate of PixON-RGCs linearly encodes local image contrast. Spatially offset (i.e., truly lateral inhibition of PixON-RGCs arises from spiking GABAergic amacrine cells. The receptive field organization of PixON-RGCs is independent of stimulus wavelength (i.e., achromatic. PixON-RGCs project predominantly to the dorsal lateral geniculate nucleus (dLGN of the thalamus and likely contribute to visual perception.

  3. Descending serotonergic facilitation and the antinociceptive effects of pregabalin in a rat model of osteoarthritic pain

    Directory of Open Access Journals (Sweden)

    Dolphin Annette C

    2009-08-01

    descending serotonergic facilitation plays a role in mediating the brush and innocuous mechanical punctate evoked neuronal responses in MIA rats, suggesting an adaptive change in the excitatory serotonergic drive modulating low threshold evoked neuronal responses in MIA-induced OA pain. This alteration in excitatory serotonergic drive, alongside an increase in α2δ-1 mRNA levels, may underlie pregabalin's state dependent effects in this model of chronic pain.

  4. Prenatal ethanol exposure reduces the effects of excitatory amino acids in the rat hippocampus

    International Nuclear Information System (INIS)

    Noble, E.P.; Ritchie, T.

    1989-01-01

    Chronic alcohol ingestion during pregnancy can lead to the Fetal Alcohol Syndrome (FAS), a disorder marked by learning disabilities. A rat model of FAS was used by introducing pregnant Sprague-Dawley rats to a liquid diet containing 35% ethanol-derived calories (E), while a second group was pair-fed an isocaloric liquid diet without ethanol (P). A third group of pregnant dams received ad libitum lab chow (C). At parturition, pups from the E and P groups were cross fostered by C mothers and all groups received lab chow. During adulthood, male offspring were sacrificed and hippocampal and prefrontal cortical slices were prelabeled with [3H]inositol. Phosphoinositide (PI) hydrolysis was determined by measuring the accumulation of [3H]inositol phosphates in the presence of LiCl in response to activation of various excitatory amino acid (EAA) receptors. In hippocampal slices, ibotenate- and quisqualate-induced PI hydrolysis was reduced in E compared to P and C animals. Moreover, the inhibitory effect of N-methyl-D-aspartate (NMDA) on carbachol-induced PI hydrolysis, evident in P and C animals, was completely abolished in the hippocampus of E animals. In contrast, in the prefrontal cerebral cortex, this inhibitory effect of NMDA prevailed even in the E animals. The evidence suggests that prenatal ethanol exposure alters the activity of EAA receptors in the hippocampal generation of 2nd messengers

  5. Principal cell spiking, postsynaptic excitation, and oxygen consumption in the rat cerebellar cortex

    DEFF Research Database (Denmark)

    Thomsen, Kirsten; Piilgaard, Henning; Gjedde, Albert

    2009-01-01

    excitatory synaptic input. Subsequent inhibition of action potential propagation and neurotransmission by blocking voltage-gated Na+-channels eliminated the increases in CMRO2 due to PF stimulation and increased PC spiking, but left a large fraction of CMRO2, i.e., basal CMRO2, intact. In conclusion, whereas......) of postsynaptic excitation and PC spiking during evoked and ongoing neuronal activity in the rat. By inhibiting excitatory synaptic input using ionotropic glutamate receptor blockers, we found that the increase in CMRO2 evoked by parallel fiber (PF) stimulation depended entirely on postsynaptic excitation...... basal CMRO2 in anesthetized animals did not seem to be related to neurosignaling, increases in CMRO2 could be induced by all aspects of neurosignaling. Our findings imply that CMRO2 responses cannot a priori be assigned to specific neuronal activities....

  6. Stimulus specificity of a steady-state visual-evoked potential-based brain-computer interface

    Science.gov (United States)

    Ng, Kian B.; Bradley, Andrew P.; Cunnington, Ross

    2012-06-01

    The mechanisms of neural excitation and inhibition when given a visual stimulus are well studied. It has been established that changing stimulus specificity such as luminance contrast or spatial frequency can alter the neuronal activity and thus modulate the visual-evoked response. In this paper, we study the effect that stimulus specificity has on the classification performance of a steady-state visual-evoked potential-based brain-computer interface (SSVEP-BCI). For example, we investigate how closely two visual stimuli can be placed before they compete for neural representation in the cortex and thus influence BCI classification accuracy. We characterize stimulus specificity using the four stimulus parameters commonly encountered in SSVEP-BCI design: temporal frequency, spatial size, number of simultaneously displayed stimuli and their spatial proximity. By varying these quantities and measuring the SSVEP-BCI classification accuracy, we are able to determine the parameters that provide optimal performance. Our results show that superior SSVEP-BCI accuracy is attained when stimuli are placed spatially more than 5° apart, with size that subtends at least 2° of visual angle, when using a tagging frequency of between high alpha and beta band. These findings may assist in deciding the stimulus parameters for optimal SSVEP-BCI design.

  7. Central amygdalar nucleus treated with orexin neuropeptides evoke differing feeding and grooming responses in the hamster.

    Science.gov (United States)

    Alò, Raffaella; Avolio, Ennio; Mele, Maria; Di Vito, Anna; Canonaco, Marcello

    2015-04-15

    Interaction of the orexinergic (ORXergic) neuronal system with the excitatory (glutamate, l-Glu) or the inhibitory (GABA) neurosignaling complexes evokes major homeostatic physiological events. In this study, effects of the two ORXergic neuropeptides (ORX-A/B) on their receptor (ORX-2R) expression changes were correlated to feeding and grooming actions of the hibernating hamster (Mesocricetus auratus). Infusion of the central amygdala nucleus (CeA) with ORX-A caused hamsters to consume notable quantities of food, while ORX-B accounted for a moderate increase. Interestingly the latter neuropeptide was responsible for greater frequencies of grooming with respect to both controls and the hamsters treated with ORX-A. These distinct behavioral changes turned out to be even greater in the presence of l-Glu agonist (NMDA) while the α1 GABAA receptor agonist (zolpidem, Zol) greatly reduced ORX-A-dependent feeding bouts. Moreover, ORX-A+NMDA mainly promoted greater ORX-2R expression levels with respect to ORX-A-treated hamsters while ORX-B+Zol was instead largely responsible for a down-regulatory trend. Overall, these features point to CeA ORX-2R sites as key sensory limbic elements capable of regulating eating and grooming responses, which may provide useful insights regarding the type of molecular mechanism(s) operating during feeding bouts. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Recovery function of the human brain stem auditory-evoked potential.

    Science.gov (United States)

    Kevanishvili, Z; Lagidze, Z

    1979-01-01

    Amplitude reduction and peak latency prolongation were observed in the human brain stem auditory-evoked potential (BEP) with preceding (conditioning) stimulation. At a conditioning interval (CI) of 5 ms the alteration of BEP was greater than at a CI of 10 ms. At a CI of 10 ms the amplitudes of some BEP components (e.g. waves I and II) were more decreased than those of others (e.g. wave V), while the peak latency prolongation did not show any obvious component selectivity. At a CI of 5 ms, the extent of the amplitude decrement of individual BEP components differed less, while the increase in the peak latencies of the later components was greater than that of the earlier components. The alterations of the parameters of the test BEPs at both CIs are ascribed to the desynchronization of intrinsic neural events. The differential amplitude reduction at a CI of 10 ms is explained by the different durations of neural firings determining various effects of desynchronization upon the amplitudes of individual BEP components. The decrease in the extent of the component selectivity and the preferential increase in the peak latencies of the later BEP components observed at a CI of 5 ms are explained by the intensification of the mechanism of the relative refractory period.

  9. Cortical evoked potentials to an auditory illusion: binaural beats.

    Science.gov (United States)

    Pratt, Hillel; Starr, Arnold; Michalewski, Henry J; Dimitrijevic, Andrew; Bleich, Naomi; Mittelman, Nomi

    2009-08-01

    To define brain activity corresponding to an auditory illusion of 3 and 6Hz binaural beats in 250Hz or 1000Hz base frequencies, and compare it to the sound onset response. Event-Related Potentials (ERPs) were recorded in response to unmodulated tones of 250 or 1000Hz to one ear and 3 or 6Hz higher to the other, creating an illusion of amplitude modulations (beats) of 3Hz and 6Hz, in base frequencies of 250Hz and 1000Hz. Tones were 2000ms in duration and presented with approximately 1s intervals. Latency, amplitude and source current density estimates of ERP components to tone onset and subsequent beats-evoked oscillations were determined and compared across beat frequencies with both base frequencies. All stimuli evoked tone-onset P(50), N(100) and P(200) components followed by oscillations corresponding to the beat frequency, and a subsequent tone-offset complex. Beats-evoked oscillations were higher in amplitude with the low base frequency and to the low beat frequency. Sources of the beats-evoked oscillations across all stimulus conditions located mostly to left lateral and inferior temporal lobe areas in all stimulus conditions. Onset-evoked components were not different across stimulus conditions; P(50) had significantly different sources than the beats-evoked oscillations; and N(100) and P(200) sources located to the same temporal lobe regions as beats-evoked oscillations, but were bilateral and also included frontal and parietal contributions. Neural activity with slightly different volley frequencies from left and right ear converges and interacts in the central auditory brainstem pathways to generate beats of neural activity to modulate activities in the left temporal lobe, giving rise to the illusion of binaural beats. Cortical potentials recorded to binaural beats are distinct from onset responses. Brain activity corresponding to an auditory illusion of low frequency beats can be recorded from the scalp.

  10. Brain correlates of music-evoked emotions.

    Science.gov (United States)

    Koelsch, Stefan

    2014-03-01

    Music is a universal feature of human societies, partly owing to its power to evoke strong emotions and influence moods. During the past decade, the investigation of the neural correlates of music-evoked emotions has been invaluable for the understanding of human emotion. Functional neuroimaging studies on music and emotion show that music can modulate activity in brain structures that are known to be crucially involved in emotion, such as the amygdala, nucleus accumbens, hypothalamus, hippocampus, insula, cingulate cortex and orbitofrontal cortex. The potential of music to modulate activity in these structures has important implications for the use of music in the treatment of psychiatric and neurological disorders.

  11. An inventory and update of jealousy-evoking partner behaviours in modern society.

    NARCIS (Netherlands)

    Dijkstra, Pieternel; Barelds, Dick P. H.; Groothof, Hinke A. K.

    2010-01-01

    The goal of the present study was to identify the most important jealousy-evoking partner behaviours and to examine the extent to which these behaviours evoke jealousy. Based on the literature, a questionnaire was constructed containing 42 jealousy-evoking partner behaviours, including a partner's

  12. Making of a Synapse: Recurrent Roles of Drebrin A at Excitatory Synapses Throughout Life.

    Science.gov (United States)

    Aoki, Chiye; Sherpa, Ang D

    2017-01-01

    Mature excitatory synapses are composed of more than 1500 proteins postsynaptically and hundreds more that operate presynaptically. Among them, drebrin is an F-actin-binding protein that increases noticeably during juvenile synaptogenesis. Electron microscopic analysis reveals that drebrin is highly enriched specifically on the postsynaptic side of excitatory synapses. Since dendritic spines are structures specialized for excitatory synaptic transmission, the function of drebrin was probed by analyzing the ultrastructural characteristics of dendritic spines of animals with genetic deletion of drebrin A (DAKO), the adult isoform of drebrin. Electron microscopic analyses revealed that these brains are surprisingly intact, in that axo-spinous synaptic junctions are well-formed and not significantly altered in number. This normal ultrastructure may be because drebrin E, the alternate embryonic isoform, compensates for the genetic deletion of drebrin A. However, DAKO results in the loss of homeostatic plasticity of N-methyl-D-aspartate receptors (NMDARs). The NMDAR activation-dependent trafficking of the NR2A subunit-containing NMDARs from dendritic shafts into spine head cytoplasm is greatly diminished within brains of DAKO. Conversely, within brains of wild-type rodents, spines respond to NMDAR blockade with influx of F-actin, drebrin A, and NR2A subunits of NMDARs. These observations indicate that drebrin A facilitates the trafficking of NMDAR cargos in an F-actin-dependent manner to mediate homeostatic plasticity. Analysis of the brains of transgenic mice used as models of Alzheimer's disease (AD) reveals that the loss of drebrin from dendritic spines predates the emergence of synaptic dysfunction and cognitive impairment, suggesting that this form of homeostatic plasticity contributes toward cognition. Two studies suggest that the nature of drebrin's interaction with NMDARs is dependent on the receptor's subunit composition. Drebrin A can be found co

  13. Diurnal rhythms in neurexins transcripts and inhibitory/excitatory synapse scaffold proteins in the biological clock.

    Directory of Open Access Journals (Sweden)

    Mika Shapiro-Reznik

    Full Text Available The neurexin genes (NRXN1/2/3 encode two families (α and β of highly polymorphic presynaptic proteins that are involved in excitatory/inhibitory synaptic balance. Recent studies indicate that neuronal activation and memory formation affect NRXN1/2/3α expression and alternative splicing at splice sites 3 and 4 (SS#3/SS#4. Neurons in the biological clock residing in the suprachiasmatic nuclei of the hypothalamus (SCN act as self-sustained oscillators, generating rhythms in gene expression and electrical activity, to entrain circadian bodily rhythms to the 24 hours day/night cycles. Cell autonomous oscillations in NRXN1/2/3α expression and SS#3/SS#4 exons splicing and their links to rhythms in excitatory/inhibitory synaptic balance in the circadian clock were explored. NRXN1/2/3α expression and SS#3/SS#4 splicing, levels of neurexin-2α and the synaptic scaffolding proteins PSD-95 and gephyrin (representing excitatory and inhibitory synapses, respectively were studied in mRNA and protein extracts obtained from SCN of C3H/J mice at different times of the 24 hours day/night cycle. Further studies explored the circadian oscillations in these components and causality relationships in immortalized rat SCN2.2 cells. Diurnal rhythms in mNRXN1α and mNRXN2α transcription, SS#3/SS#4 exon-inclusion and PSD-95 gephyrin and neurexin-2α levels were found in the SCN in vivo. No such rhythms were found with mNRXN3α. SCN2.2 cells also exhibited autonomous circadian rhythms in rNRXN1/2 expression SS#3/SS#4 exon inclusion and PSD-95, gephyrin and neurexin-2α levels. rNRXN3α and rNRXN1/2β were not expressed. Causal relationships were demonstrated, by use of specific siRNAs, between rNRXN2α SS#3 exon included transcripts and gephyrin levels in the SCN2.2 cells. These results show for the first time dynamic, cell autonomous, diurnal rhythms in expression and splicing of NRXN1/2 and subsequent effects on the expression of neurexin-2α and postsynaptic

  14. The influence of single bursts vs. single spikes at excitatory dendrodendritic synapses

    Science.gov (United States)

    Masurkar, Arjun V.; Chen, Wei R.

    2015-01-01

    The synchronization of neuronal activity is thought to enhance information processing. There is much evidence supporting rhythmically bursting external tufted cells (ETCs) of the rodent olfactory bulb glomeruli coordinating the activation of glomerular interneurons and mitral cells via dendrodendritic excitation. However, as bursting has variable significance at axodendritic cortical synapses, it is not clear if ETC bursting imparts a specific functional advantage over the preliminary spike in dendrodendritic synaptic networks. To answer this question, we investigated the influence of single ETC bursts and spikes with the in-vitro rat olfactory bulb preparation at different levels of processing, via calcium imaging of presynaptic ETC dendrites, dual electrical recording of ETC–interneuron synaptic pairs, and multicellular calcium imaging of ETC-induced population activity. Our findings supported single ETC bursts, vs. single spikes, driving robust presynaptic calcium signaling, which in turn was associated with profound extension of the initial monosynaptic spike-driven dendrodendritic excitatory postsynaptic potential. This extension could be driven by either the spike-dependent or spike-independent components of the burst. At the population level, burst-induced excitation was more widespread and reliable compared with single spikes. This further supports the ETC network, in part due to a functional advantage of bursting at excitatory dendrodendritic synapses, coordinating synchronous activity at behaviorally relevant frequencies related to odor processing in vivo. PMID:22277089

  15. Astrocytic energetics during excitatory neurotransmission: What are contributions of glutamate oxidation and glycolysis?

    OpenAIRE

    Dienel, Gerald A.

    2013-01-01

    Astrocytic energetics of excitatory neurotransmission is controversial due to discrepant findings in different experimental systems in vitro and in vivo. The energy requirements of glutamate uptake are believed by some researchers to be satisfied by glycolysis coupled with shuttling of lactate to neurons for oxidation. However, astrocytes increase glycogenolysis and oxidative metabolism during sensory stimulation in vivo, indicating that other sources of energy are used by astrocytes during b...

  16. Amyloid precursor protein overexpression depresses excitatory transmission through both presynaptic and postsynaptic mechanisms

    OpenAIRE

    Ting, Jonathan T.; Kelley, Brooke G.; Lambert, Talley J.; Cook, David G.; Sullivan, Jane M.

    2006-01-01

    Overexpression of the amyloid precursor protein (APP) in hippocampal neurons leads to elevated β-amyloid peptide (Aβ) production and consequent depression of excitatory transmission. The precise mechanisms underlying APP-induced synaptic depression are poorly understood. Uncovering these mechanisms could provide insight into how neuronal function is compromised before cell death during the early stages of Alzheimer's disease. Here we verify that APP up-regulation leads to depression of transm...

  17. A preconscious neural mechanism of hypnotically altered colors: a double case study.

    Directory of Open Access Journals (Sweden)

    Mika Koivisto

    Full Text Available Hypnotic suggestions may change the perceived color of objects. Given that chromatic stimulus information is processed rapidly and automatically by the visual system, how can hypnotic suggestions affect perceived colors in a seemingly immediate fashion? We studied the mechanisms of such color alterations by measuring electroencephalography in two highly suggestible participants as they perceived briefly presented visual shapes under posthypnotic color alternation suggestions such as "all the squares are blue". One participant consistently reported seeing the suggested colors. Her reports correlated with enhanced evoked upper beta-band activity (22 Hz 70-120 ms after stimulus in response to the shapes mentioned in the suggestion. This effect was not observed in a control condition where the participants merely tried to simulate the effects of the suggestion on behavior. The second participant neither reported color alterations nor showed the evoked beta activity, although her subjective experience and event-related potentials were changed by the suggestions. The results indicate a preconscious mechanism that first compares early visual input with a memory representation of the suggestion and consequently triggers the color alteration process in response to the objects specified by the suggestion. Conscious color experience is not purely the result of bottom-up processing but it can be modulated, at least in some individuals, by top-down factors such as hypnotic suggestions.

  18. Music-evoked emotions: principles, brain correlates, and implications for therapy.

    Science.gov (United States)

    Koelsch, Stefan

    2015-03-01

    This paper describes principles underlying the evocation of emotion with music: evaluation, resonance, memory, expectancy/tension, imagination, understanding, and social functions. Each of these principles includes several subprinciples, and the framework on music-evoked emotions emerging from these principles and subprinciples is supposed to provide a starting point for a systematic, coherent, and comprehensive theory on music-evoked emotions that considers both reception and production of music, as well as the relevance of emotion-evoking principles for music therapy. © 2015 New York Academy of Sciences.

  19. Vibration and muscle contraction affect somatosensory evoked potentials

    OpenAIRE

    Cohen, LG; Starr, A

    1985-01-01

    We recorded potentials evoked by specific somatosensory stimuli over peripheral nerve, spinal cord, and cerebral cortex. Vibration attenuated spinal and cerebral potentials evoked by mixed nerve and muscle spindle stimulation; in one subject that was tested, there was no effect on cutaneous input. Presynaptic inhibition of Ia input in the spinal cord and muscle spindle receptor occupancy are probably the responsible mechanisms. In contrast, muscle contraction attenuated cerebral potentials to...

  20. Pathway and Cell-Specific Kappa-Opioid Receptor Modulation of Excitatory-Inhibitory Balance Differentially Gates D1 and D2 Accumbens Neuron Activity

    Science.gov (United States)

    Tejeda, Hugo A.; Wu, Jocelyn; Kornspun, Alana R.; Pignatelli, Marco; Kashtelyan, Vadim; Krashes, Michael J.; Lowell, Brad B.; Carlezon, William A.; Bonci, Antonello

    2018-01-01

    Endogenous dynorphin signaling via the kappa-opioid receptor (KOR) in the nucleus accumbens (NAcc) powerfully mediates negative affective states and stress reactivity. Excitatory inputs from the hippocampus and amygdala play a fundamental role in shaping the activity of both NAcc D1 and D2 MSNs, which encode positive and negative motivational valences, respectively. However, a circuit-based mechanism by which KOR modulation of excitation-inhibition balance modifies D1 and D2 MSN activity is lacking. Here, we provide a comprehensive synaptic framework wherein presynaptic KOR inhibition decreases excitatory drive of D1 MSN activity by the amygdala, but not hippocampus. Conversely, presynaptic inhibition by KORs of inhibitory synapses on D2 MSNs enhances integration of excitatory drive by the amygdala and hippocampus. In conclusion, we describe a circuit-based mechanism showing differential gating of afferent control of D1 and D2 MSN activity by KORs in a pathway specific manner. PMID:28056342

  1. Muscle synergies evoked by microstimulation are preferentially encoded during behavior

    Directory of Open Access Journals (Sweden)

    Simon Alexander Overduin

    2014-03-01

    Full Text Available Electrical microstimulation studies provide some of the most direct evidence for the neural representation of muscle synergies. These synergies, i.e. coordinated activations of groups of muscles, have been proposed as building blocks for the construction of motor behaviors by the nervous system. Intraspinal or intracortical microstimulation has been shown to evoke muscle patterns that can be resolved into a small set of synergies similar to those seen in natural behavior. However, questions remain about the validity of microstimulation as a probe of neural function, particularly given the relatively long trains of supratheshold stimuli used in these studies. Here, we examined whether muscle synergies evoked during intracortical microstimulation in two rhesus macaques were similarly encoded by nearby motor cortical units during a purely voluntary behavior involving object reach, grasp, and carry movements. At each microstimulation site we identified the synergy most strongly evoked among those extracted from muscle patterns evoked over all microstimulation sites. For each cortical unit recorded at the same microstimulation site, we then identified the synergy most strongly encoded among those extracted from muscle patterns recorded during the voluntary behavior. We found that the synergy most strongly evoked at an intracortical microstimulation site matched the synergy most strongly encoded by proximal units more often than expected by chance. These results suggest a common neural substrate for microstimulation-evoked motor responses and for the generation of muscle patterns during natural behaviors.

  2. Age-related deficits in synaptic plasticity rescued by activating PKA or PKC in sensory neurons of Aplysia californica.

    Science.gov (United States)

    Kempsell, Andrew T; Fieber, Lynne A

    2015-01-01

    Brain aging is associated with declines in synaptic function that contribute to memory loss, including reduced postsynaptic response to neurotransmitters and decreased neuronal excitability. To understand how aging affects memory in a simple neural circuit, we studied neuronal proxies of memory for sensitization in mature vs. advanced age Aplysia californica (Aplysia). L-Glutamate- (L-Glu-) evoked excitatory currents were facilitated by the neuromodulator serotonin (5-HT) in sensory neurons (SN) isolated from mature but not aged animals. Activation of protein kinase A (PKA) and protein kinase C (PKC) signaling rescued facilitation of L-Glu currents in aged SN. Similarly, PKA and PKC activators restored increased excitability in aged tail SN. These results suggest that altered synaptic plasticity during aging involves defects in second messenger systems.

  3. Evidence for an excitatory amino acid pathway in the brainstem and for its involvement in cardiovascular control.

    Science.gov (United States)

    Somogyi, P; Minson, J B; Morilak, D; Llewellyn-Smith, I; McIlhinney, J R; Chalmers, J

    1989-09-04

    The source and possible role of excitatory amino acid projections to areas of the ventrolateral medulla (VLM) involved in cardiovascular control were studied. Following the injection of [3H]D-aspartate ([3H]D-Asp), a selective tracer for excitatory amino acid pathways, into vasopressor or vasodepressor areas of the VLM in rats, more than 90% of retrogradely labelled neurones were found in the nucleus of the solitary tract (NTS). Very few of the [3H]D-Asp-labelled cells were immunoreactive for tyrosine hydroxylase, none for phenylethanolamine-N-methyltransferase or gamma-aminobutyric acid. The density of labelled cells in the NTS was similar to that obtained with the non-selective tracers wheat germ agglutinin-horseradish peroxidase (WGA-HRP) and WGA-colloidal gold, but these tracers also labelled other cell groups in the medulla. Furthermore, the decrease in blood pressure, caused by pharmacological activation of neurones in the NTS of rats, or by electrical stimulation of the aortic depressor nerve in rabbits could be blocked by the selective N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovalerate injected into the caudal vasodepressor area of the VLM. This area corresponds to the termination of [3H]D-Asp transporting NTS neurones. These results provide evidence that a population of NTS neurones projecting to the VLM use excitatory amino acids as transmitters. Among other possible functions, this pathway may mediate tonic and reflex control of blood pressure via NMDA receptors in the VLM.

  4. The involuntary nature of music-evoked autobiographical memories in Alzheimer's disease.

    Science.gov (United States)

    El Haj, Mohamad; Fasotti, Luciano; Allain, Philippe

    2012-03-01

    The main objective of this paper was to examine the involuntary nature of music-evoked autobiographical memories. For this purpose, young adults, older adults, and patients with a clinical diagnosis of probable Alzheimer's disease (AD) were asked to remember autobiographical events in two conditions: after being exposed to their own chosen music, and in silence. Compared to memories evoked in silence, memories evoked in the "Music" condition were found to be more specific, accompanied by more emotional content and impact on mood, and retrieved faster. In addition, these memories engaged less executive processes. Thus, with all these characteristics and the fact that they are activated by a perceptual cue (i.e., music), music-evoked autobiographic memories have all the features to be considered as involuntary memories. Our paper reveals several characteristics of music-evoked autobiographical memories in AD patients and offers a theoretical background for this phenomenon. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Brief Emotion Regulation Training Facilitates Arousal Control During Sexual Stimuli

    NARCIS (Netherlands)

    van Overveld, Mark; Borg, Charmaine

    2015-01-01

    Disgust, a negative emotion which evokes strong behavioral avoidance tendencies, has been associated with sexual dysfunction. Recently, it was postulated that healthy sexual functioning requires a balance between excitatory (increased sexual arousal) and inhibitory processes (lowered disgust

  6. Noise exposure alters long-term neural firing rates and synchrony in primary auditory and rostral belt cortices following bimodal stimulation.

    Science.gov (United States)

    Takacs, Joseph D; Forrest, Taylor J; Basura, Gregory J

    2017-12-01

    We previously demonstrated that bimodal stimulation (spinal trigeminal nucleus [Sp5] paired with best frequency tone) altered neural tone-evoked and spontaneous firing rates (SFRs) in primary auditory cortex (A1) 15 min after pairing in guinea pigs with and without noise-induced tinnitus. Neural responses were enhanced (+10 ms) or suppressed (0 ms) based on the bimodal pairing interval. Here we investigated whether bimodal stimulation leads to long-term (up to 2 h) changes in tone-evoked and SFRs and neural synchrony (correlate of tinnitus) and if the long-term bimodal effects are altered following noise exposure. To obviate the effects of permanent hearing loss on the results, firing rates and neural synchrony were measured three weeks following unilateral (left ear) noise exposure and a temporary threshold shift. Simultaneous extra-cellular single-unit recordings were made from contralateral (to noise) A1 and dorsal rostral belt (RB); an associative auditory cortical region thought to influence A1, before and after bimodal stimulation (pairing intervals of 0 ms; simultaneous Sp5-tone and +10 ms; Sp5 precedes tone). Sixty and 120 min after 0 ms pairing tone-evoked and SFRs were suppressed in sham A1; an effect only preserved 120 min following pairing in noise. Stimulation at +10 ms only affected SFRs 120 min after pairing in sham and noise-exposed A1. Within sham RB, pairing at 0 and +10 ms persistently suppressed tone-evoked and SFRs, while 0 ms pairing in noise markedly enhanced tone-evoked and SFRs up to 2 h. Together, these findings suggest that bimodal stimulation has long-lasting effects in A1 that also extend to the associative RB that is altered by noise and may have persistent implications for how noise damaged brains process multi-sensory information. Moreover, prior to bimodal stimulation, noise damage increased neural synchrony in A1, RB and between A1 and RB neurons. Bimodal stimulation led to persistent changes in neural synchrony in

  7. Altered cortical GABA neurotransmission in schizophrenia: insights into novel therapeutic strategies.

    Science.gov (United States)

    Stan, Ana D; Lewis, David A

    2012-06-01

    Altered markers of cortical GABA neurotransmission are among the most consistently observed abnormalities in postmortem studies of schizophrenia. The altered markers are particularly evident between the chandelier class of GABA neurons and their synaptic targets, the axon initial segment (AIS) of pyramidal neurons. For example, in the dorsolateral prefrontal cortex of subjects with schizophrenia immunoreactivity for the GABA membrane transporter is decreased in presynaptic chandelier neuron axon terminals, whereas immunoreactivity for the GABAA receptor α2 subunit is increased in postsynaptic AIS. Both of these molecular changes appear to be compensatory responses to a presynaptic deficit in GABA synthesis, and thus could represent targets for novel therapeutic strategies intended to augment the brain's own compensatory mechanisms. Recent findings that GABA inputs from neocortical chandelier neurons can be powerfully excitatory provide new ideas about the role of these neurons in the pathophysiology of cortical dysfunction in schizophrenia, and consequently in the design of pharmacological interventions.

  8. Circuit variability interacts with excitatory-inhibitory diversity of interneurons to regulate network encoding capacity.

    Science.gov (United States)

    Tsai, Kuo-Ting; Hu, Chin-Kun; Li, Kuan-Wei; Hwang, Wen-Liang; Chou, Ya-Hui

    2018-05-23

    Local interneurons (LNs) in the Drosophila olfactory system exhibit neuronal diversity and variability, yet it is still unknown how these features impact information encoding capacity and reliability in a complex LN network. We employed two strategies to construct a diverse excitatory-inhibitory neural network beginning with a ring network structure and then introduced distinct types of inhibitory interneurons and circuit variability to the simulated network. The continuity of activity within the node ensemble (oscillation pattern) was used as a readout to describe the temporal dynamics of network activity. We found that inhibitory interneurons enhance the encoding capacity by protecting the network from extremely short activation periods when the network wiring complexity is very high. In addition, distinct types of interneurons have differential effects on encoding capacity and reliability. Circuit variability may enhance the encoding reliability, with or without compromising encoding capacity. Therefore, we have described how circuit variability of interneurons may interact with excitatory-inhibitory diversity to enhance the encoding capacity and distinguishability of neural networks. In this work, we evaluate the effects of different types and degrees of connection diversity on a ring model, which may simulate interneuron networks in the Drosophila olfactory system or other biological systems.

  9. Up-Regulation of Excitatory Amino Acid Transporters EAAT1 and EAAT2 by ß-Klotho

    Directory of Open Access Journals (Sweden)

    Jamshed Warsi

    2015-12-01

    Full Text Available Background/Aims: Klotho, a transmembrane protein expressed in chorioid plexus of the brain, kidney, and several other tissues, is required for inhibition of 1,25(OH2D3 formation by FGF23. The extracellular domain of Klotho protein could be cleaved off, thus being released into blood or cerebrospinal fluid. At least in part by exerting β-glucuronidase activity, soluble klotho regulates several ion channels and carriers. Klotho protein deficiency accelerates the appearance of age related disorders including neurodegeneration and muscle wasting and eventually leads to premature death. The present study explored the effect of Klotho protein on the excitatory glutamate transporters EAAT1 (SLC1A3 and EAAT2 (SLC1A2, Na+ coupled carriers clearing excitatory amino acids from the synaptic cleft and thus participating in the regulation of neuronal excitability. Methods: cRNA encoding EAAT1 or EAAT2 was injected into Xenopus laevis oocytes and glutamate (2 mM-induced inward current (IGlu taken as measure of glutamate transport. Measurements were made without or with prior 24 h treatment with soluble ß-Klotho protein (30 ng/ml in the absence and presence of β-glucuronidase inhibitor D-saccharic acid 1,4-lactone monohydrate (DSAL,10 µM. Results: IGlu was observed in EAAT1 and in EAAT2 expressing oocytes but not in water injected oocytes. In both, EAAT1 and EAAT2 expressing oocytes IGlu was significantly increased by treatment with soluble ß-Klotho protein, an effect reversed by DSAL. Treatment with ß-klotho protein increased significantly the maximal transport rate without significantly modifying the affinity of the carriers. Conclusion: ß-Klotho up-regulates the excitatory glutamate transporters EAAT1 and EAAT2 and thus participates in the regulation of neuronal excitation.

  10. Gender differences in binaural speech-evoked auditory brainstem response: are they clinically significant?

    Science.gov (United States)

    Jalaei, Bahram; Azmi, Mohd Hafiz Afifi Mohd; Zakaria, Mohd Normani

    2018-05-17

    Binaurally evoked auditory evoked potentials have good diagnostic values when testing subjects with central auditory deficits. The literature on speech-evoked auditory brainstem response evoked by binaural stimulation is in fact limited. Gender disparities in speech-evoked auditory brainstem response results have been consistently noted but the magnitude of gender difference has not been reported. The present study aimed to compare the magnitude of gender difference in speech-evoked auditory brainstem response results between monaural and binaural stimulations. A total of 34 healthy Asian adults aged 19-30 years participated in this comparative study. Eighteen of them were females (mean age=23.6±2.3 years) and the remaining sixteen were males (mean age=22.0±2.3 years). For each subject, speech-evoked auditory brainstem response was recorded with the synthesized syllable /da/ presented monaurally and binaurally. While latencies were not affected (p>0.05), the binaural stimulation produced statistically higher speech-evoked auditory brainstem response amplitudes than the monaural stimulation (p0.80), substantive gender differences were noted in most of speech-evoked auditory brainstem response peaks for both stimulation modes. The magnitude of gender difference between the two stimulation modes revealed some distinct patterns. Based on these clinically significant results, gender-specific normative data are highly recommended when using speech-evoked auditory brainstem response for clinical and future applications. The preliminary normative data provided in the present study can serve as the reference for future studies on this test among Asian adults. Copyright © 2018 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  11. 4-aminopyridine in scala media reversibly alters the cochlear potentials and suppresses electrically evoked oto-acoustic emissions.

    Science.gov (United States)

    Kirk, D L; Yates, G K

    1998-01-01

    Iontophoresis of 4-aminopyridine into scala media of the guinea pig cochlea caused elevation of the thresholds of the compound action potential of the auditory nerve, loss of amplitude of the extracellular cochlear microphonic response (CM), increase in the endocochlear potential (EP) and reduction in the amplitude of electrically evoked oto-acoustic emissions (EEOAEs). These changes were reversible over 10-20 min. The reciprocity of the changes in the CM and the EP was consistent with an interruption of both DC and AC currents through outer hair cells (OHCs), probably by blockade of mechano-electrical transduction (MET) channels in OHCs. Reductions in EEOAEs were consistent with the extrinsically applied generating current entering the OHC via the MET channels. Implications for the activation of OHC electromotility in vivo are discussed.

  12. Synchronization in a non-uniform network of excitatory spiking neurons

    Science.gov (United States)

    Echeveste, Rodrigo; Gros, Claudius

    Spontaneous synchronization of pulse coupled elements is ubiquitous in nature and seems to be of vital importance for life. Networks of pacemaker cells in the heart, extended populations of southeast asian fireflies, and neuronal oscillations in cortical networks, are examples of this. In the present work, a rich repertoire of dynamical states with different degrees of synchronization are found in a network of excitatory-only spiking neurons connected in a non-uniform fashion. In particular, uncorrelated and partially correlated states are found without the need for inhibitory neurons or external currents. The phase transitions between these states, as well the robustness, stability, and response of the network to external stimulus are studied.

  13. Music-Evoked Emotions—Current Studies

    Science.gov (United States)

    Schaefer, Hans-Eckhardt

    2017-01-01

    The present study is focused on a review of the current state of investigating music-evoked emotions experimentally, theoretically and with respect to their therapeutic potentials. After a concise historical overview and a schematic of the hearing mechanisms, experimental studies on music listeners and on music performers are discussed, starting with the presentation of characteristic musical stimuli and the basic features of tomographic imaging of emotional activation in the brain, such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), which offer high spatial resolution in the millimeter range. The progress in correlating activation imaging in the brain to the psychological understanding of music-evoked emotion is demonstrated and some prospects for future research are outlined. Research in psychoneuroendocrinology and molecular markers is reviewed in the context of music-evoked emotions and the results indicate that the research in this area should be intensified. An assessment of studies involving measuring techniques with high temporal resolution down to the 10 ms range, as, e.g., electroencephalography (EEG), event-related brain potentials (ERP), magnetoencephalography (MEG), skin conductance response (SCR), finger temperature, and goose bump development (piloerection) can yield information on the dynamics and kinetics of emotion. Genetic investigations reviewed suggest the heredity transmission of a predilection for music. Theoretical approaches to musical emotion are directed to a unified model for experimental neurological evidence and aesthetic judgment. Finally, the reports on musical therapy are briefly outlined. The study concludes with an outlook on emerging technologies and future research fields. PMID:29225563

  14. Stimulator with arbitrary waveform for auditory evoked potentials

    International Nuclear Information System (INIS)

    Martins, H R; Romao, M; Placido, D; Provenzano, F; Tierra-Criollo, C J

    2007-01-01

    The technological improvement helps many medical areas. The audiometric exams involving the auditory evoked potentials can make better diagnoses of auditory disorders. This paper proposes the development of a stimulator based on Digital Signal Processor. This stimulator is the first step of an auditory evoked potential system based on the ADSP-BF533 EZ KIT LITE (Analog Devices Company - USA). The stimulator can generate arbitrary waveform like Sine Waves, Modulated Amplitude, Pulses, Bursts and Pips. The waveforms are generated through a graphical interface programmed in C++ in which the user can define the parameters of the waveform. Furthermore, the user can set the exam parameters as number of stimuli, time with stimulation (Time ON) and time without stimulus (Time OFF). In future works will be implemented another parts of the system that includes the acquirement of electroencephalogram and signal processing to estimate and analyze the evoked potential

  15. Stimulator with arbitrary waveform for auditory evoked potentials

    Energy Technology Data Exchange (ETDEWEB)

    Martins, H R; Romao, M; Placido, D; Provenzano, F; Tierra-Criollo, C J [Universidade Federal de Minas Gerais (UFMG), Departamento de Engenharia Eletrica (DEE), Nucleo de Estudos e Pesquisa em Engenharia Biomedica NEPEB, Av. Ant. Carlos, 6627, sala 2206, Pampulha, Belo Horizonte, MG, 31.270-901 (Brazil)

    2007-11-15

    The technological improvement helps many medical areas. The audiometric exams involving the auditory evoked potentials can make better diagnoses of auditory disorders. This paper proposes the development of a stimulator based on Digital Signal Processor. This stimulator is the first step of an auditory evoked potential system based on the ADSP-BF533 EZ KIT LITE (Analog Devices Company - USA). The stimulator can generate arbitrary waveform like Sine Waves, Modulated Amplitude, Pulses, Bursts and Pips. The waveforms are generated through a graphical interface programmed in C++ in which the user can define the parameters of the waveform. Furthermore, the user can set the exam parameters as number of stimuli, time with stimulation (Time ON) and time without stimulus (Time OFF). In future works will be implemented another parts of the system that includes the acquirement of electroencephalogram and signal processing to estimate and analyze the evoked potential.

  16. Evoking prescribed spike times in stochastic neurons

    Science.gov (United States)

    Doose, Jens; Lindner, Benjamin

    2017-09-01

    Single cell stimulation in vivo is a powerful tool to investigate the properties of single neurons and their functionality in neural networks. We present a method to determine a cell-specific stimulus that reliably evokes a prescribed spike train with high temporal precision of action potentials. We test the performance of this stimulus in simulations for two different stochastic neuron models. For a broad range of parameters and a neuron firing with intermediate firing rates (20-40 Hz) the reliability in evoking the prescribed spike train is close to its theoretical maximum that is mainly determined by the level of intrinsic noise.

  17. Visual evoked potentials in patients after methanol poisoning.

    Science.gov (United States)

    Urban, Pavel; Zakharov, Sergey; Diblík, Pavel; Pelclová, Daniela; Ridzoň, Petr

    2016-01-01

    We report the results of the visual evoked potentials (VEP) examination in patients after severe poisoning by methanol. The group of 47 patients (38 males and 9 females) was assembled out of persons who survived an outbreak of poisoning by the methanol adulterated alcohol beverages, which happened in the Czech Republic in 2012-2013. The visual evoked potentials examination was performed using monocular checkerboard pattern-reversal stimulation. Two criteria of abnormality were chosen: missing evoked response, and wave P1 latency > 117 ms. Non-parametric statistical methods (median, range, and the median test) were used to analyze factors influencing the VEP abnormality. The visual evoked potential was abnormal in 20 patients (43%), 5 of them had normal visual acuity on the Snellen chart. The VEP abnormality did not correlate significantly with initial serum concentrations of methanol, formic acid or lactate; however, it showed statistically significant inverse relation to the initial serum pH: the subgroup with the abnormal VEP had significantly lower median pH in comparison with the subgroup with the normal VEP (7.16 vs. 7.34, p = 0.04). The abnormality was not related to chronic alcohol abuse. The visual evoked potentials examination appeared sensitive enough to detected even subclinical impairment of the optic system. Metabolic acidosis is likely to be the key factor related to the development of visual damage induced by methanol. The examination performed with a delay of 1-9 months after the poisoning documented the situation relatively early after the event. It is considered as a baseline for the planned long-term follow-up of the patients, which will make it possible to assess the dynamics of the observed changes, their reversibility, and the occurrence of potential late sequelae. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

  18. Heat pulse excitability of vestibular hair cells and afferent neurons.

    Science.gov (United States)

    Rabbitt, Richard D; Brichta, Alan M; Tabatabaee, Hessam; Boutros, Peter J; Ahn, JoongHo; Della Santina, Charles C; Poppi, Lauren A; Lim, Rebecca

    2016-08-01

    In the present study we combined electrophysiology with optical heat pulse stimuli to examine thermodynamics of membrane electrical excitability in mammalian vestibular hair cells and afferent neurons. We recorded whole cell currents in mammalian type II vestibular hair cells using an excised preparation (mouse) and action potentials (APs) in afferent neurons in vivo (chinchilla) in response to optical heat pulses applied to the crista (ΔT ≈ 0.25°C per pulse). Afferent spike trains evoked by heat pulse stimuli were diverse and included asynchronous inhibition, asynchronous excitation, and/or phase-locked APs synchronized to each infrared heat pulse. Thermal responses of membrane currents responsible for APs in ganglion neurons were strictly excitatory, with Q10 ≈ 2. In contrast, hair cells responded with a mix of excitatory and inhibitory currents. Excitatory hair cell membrane currents included a thermoelectric capacitive current proportional to the rate of temperature rise (dT/dt) and an inward conduction current driven by ΔT An iberiotoxin-sensitive inhibitory conduction current was also evoked by ΔT, rising in protein biophysics and manipulate cellular excitability. Copyright © 2016 the American Physiological Society.

  19. Evoked Emotions Predict Food Choice

    NARCIS (Netherlands)

    Dalenberg, Jelle R.; Gutjar, Swetlana; ter Horst, Gert J.; de Graaf, Kees; Renken, Remco J.; Jager, Gerry

    2014-01-01

    In the current study we show that non-verbal food-evoked emotion scores significantly improve food choice prediction over merely liking scores. Previous research has shown that liking measures correlate with choice. However, liking is no strong predictor for food choice in real life environments.

  20. The influence of single bursts versus single spikes at excitatory dendrodendritic synapses.

    Science.gov (United States)

    Masurkar, Arjun V; Chen, Wei R

    2012-02-01

    The synchronization of neuronal activity is thought to enhance information processing. There is much evidence supporting rhythmically bursting external tufted cells (ETCs) of the rodent olfactory bulb glomeruli coordinating the activation of glomerular interneurons and mitral cells via dendrodendritic excitation. However, as bursting has variable significance at axodendritic cortical synapses, it is not clear if ETC bursting imparts a specific functional advantage over the preliminary spike in dendrodendritic synaptic networks. To answer this question, we investigated the influence of single ETC bursts and spikes with the in vitro rat olfactory bulb preparation at different levels of processing, via calcium imaging of presynaptic ETC dendrites, dual electrical recording of ETC -interneuron synaptic pairs, and multicellular calcium imaging of ETC-induced population activity. Our findings supported single ETC bursts, versus single spikes, driving robust presynaptic calcium signaling, which in turn was associated with profound extension of the initial monosynaptic spike-driven dendrodendritic excitatory postsynaptic potential. This extension could be driven by either the spike-dependent or spike-independent components of the burst. At the population level, burst-induced excitation was more widespread and reliable compared with single spikes. This further supports the ETC network, in part due to a functional advantage of bursting at excitatory dendrodendritic synapses, coordinating synchronous activity at behaviorally relevant frequencies related to odor processing in vivo. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  1. The effects of curiosity-evoking events on activity enjoyment.

    Science.gov (United States)

    Isikman, Elif; MacInnis, Deborah J; Ülkümen, Gülden; Cavanaugh, Lisa A

    2016-09-01

    Whereas prior literature has studied the positive effects of curiosity-evoking events that are integral to focal activities, we explore whether and how a curiosity-evoking event that is incidental to a focal activity induces negative outcomes for enjoyment. Four experiments and 1 field study demonstrate that curiosity about an event that is incidental to an activity in which individuals are engaged, significantly affects enjoyment of a concurrent activity. The reason why is that curiosity diverts attention away from the concurrent activity and focuses attention on the curiosity-evoking event. Thus, curiosity regarding an incidental event decreases enjoyment of a positive focal activity but increases enjoyment of a negative focal activity. PsycINFO Database Record (c) 2016 APA, all rights reserved

  2. Paraventricular Nucleus Modulates Excitatory Cardiovascular Reflexes during Electroacupuncture

    Science.gov (United States)

    Tjen-A-Looi, Stephanie C.; Guo, Zhi-Ling; Fu, Liang-Wu; Longhurst, John C.

    2016-01-01

    The paraventricular nucleus (PVN) regulates sympathetic outflow and blood pressure. Somatic afferent stimulation activates neurons in the hypothalamic PVN. Parvocellular PVN neurons project to sympathoexcitatory cardiovascular regions of the rostral ventrolateral medulla (rVLM). Electroacupuncture (EA) stimulates the median nerve (P5-P6) to modulate sympathoexcitatory responses. We hypothesized that the PVN and its projections to the rVLM participate in the EA-modulation of sympathoexcitatory cardiovascular responses. Cats were anesthetized and ventilated. Heart rate and mean blood pressure were monitored. Application of bradykinin every 10-min on the gallbladder induced consistent pressor reflex responses. Thirty-min of bilateral EA stimulation at acupoints P5-P6 reduced the pressor responses for at least 60-min. Inhibition of the PVN with naloxone reversed the EA-inhibition. Responses of cardiovascular barosensitive rVLM neurons evoked by splanchnic nerve stimulation were reduced by EA and then restored with opioid receptor blockade in the PVN. EA at P5-P6 decreased splanchnic evoked activity of cardiovascular barosensitive PVN neurons that also project directly to the rVLM. PVN neurons labeled with retrograde tracer from rVLM were co-labeled with μ-opioid receptors and juxtaposed to endorphinergic fibers. Thus, the PVN and its projection to rVLM are important in processing acupuncture modulation of elevated blood pressure responses through a PVN opioid mechanism. PMID:27181844

  3. High frequency oscillations evoked by peripheral magnetic stimulation.

    Science.gov (United States)

    Biller, S; Simon, L; Fiedler, P; Strohmeier, D; Haueisen, J

    2011-01-01

    The analysis of somatosensory evoked potentials (SEP) and / or fields (SEF) is a well-established and important tool for investigating the functioning of the peripheral and central human nervous system. A standard technique to evoke SEPs / SEFs is the stimulation of the median nerve by using a bipolar electrical stimulus. We aim at an alternative stimulation technique enabling stimulation of deep nerve structures while reducing patient stress and error susceptibility. In the current study, we apply a commercial transcranial magnetic stimulation system for peripheral magnetic stimulation of the median nerve. We compare the results of simultaneously recorded EEG signals to prove applicability of our technique to evoke SEPs including low frequency components (LFC) as well as high frequency oscillations (HFO). Therefore, we compare amplitude, latency and time-frequency characteristics of the SEP of 14 healthy volunteers after electric and magnetic stimulation. Both low frequency components and high frequency oscillations were detected. The HFOs were superimposed onto the primary cortical response N20. Statistical analysis revealed significantly lower amplitudes and increased latencies for LFC and HFO components after magnetic stimulation. The differences indicate the inability of magnetic stimulation to elicit supramaximal responses. A psycho-perceptual evaluation showed that magnetic stimulation was less unpleasant for 12 out of the 14 volunteers. In conclusion, we showed that LFC and HFO components related to median nerve stimulation can be evoked by peripheral magnetic stimulation.

  4. Optimal properties of analog perceptrons with excitatory weights.

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    Claudia Clopath

    Full Text Available The cerebellum is a brain structure which has been traditionally devoted to supervised learning. According to this theory, plasticity at the Parallel Fiber (PF to Purkinje Cell (PC synapses is guided by the Climbing fibers (CF, which encode an 'error signal'. Purkinje cells have thus been modeled as perceptrons, learning input/output binary associations. At maximal capacity, a perceptron with excitatory weights expresses a large fraction of zero-weight synapses, in agreement with experimental findings. However, numerous experiments indicate that the firing rate of Purkinje cells varies in an analog, not binary, manner. In this paper, we study the perceptron with analog inputs and outputs. We show that the optimal input has a sparse binary distribution, in good agreement with the burst firing of the Granule cells. In addition, we show that the weight distribution consists of a large fraction of silent synapses, as in previously studied binary perceptron models, and as seen experimentally.

  5. Inferring Trial-to-Trial Excitatory and Inhibitory Synaptic Inputs from Membrane Potential using Gaussian Mixture Kalman Filtering

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    Milad eLankarany

    2013-09-01

    Full Text Available Time-varying excitatory and inhibitory synaptic inputs govern activity of neurons and process information in the brain. The importance of trial-to-trial fluctuations of synaptic inputs has recently been investigated in neuroscience. Such fluctuations are ignored in the most conventional techniques because they are removed when trials are averaged during linear regression techniques. Here, we propose a novel recursive algorithm based on Gaussian mixture Kalman filtering for estimating time-varying excitatory and inhibitory synaptic inputs from single trials of noisy membrane potential in current clamp recordings. The Kalman filtering is followed by an expectation maximization algorithm to infer the statistical parameters (time-varying mean and variance of the synaptic inputs in a non-parametric manner. As our proposed algorithm is repeated recursively, the inferred parameters of the mixtures are used to initiate the next iteration. Unlike other recent algorithms, our algorithm does not assume an a priori distribution from which the synaptic inputs are generated. Instead, the algorithm recursively estimates such a distribution by fitting a Gaussian mixture model. The performance of the proposed algorithms is compared to a previously proposed PF-based algorithm (Paninski et al., 2012 with several illustrative examples, assuming that the distribution of synaptic input is unknown. If noise is small, the performance of our algorithms is similar to that of the previous one. However, if noise is large, they can significantly outperform the previous proposal. These promising results suggest that our algorithm is a robust and efficient technique for estimating time varying excitatory and inhibitory synaptic conductances from single trials of membrane potential recordings.

  6. Steady-state evoked potentials possibilities for mental-state estimation

    Science.gov (United States)

    Junker, Andrew M.; Schnurer, John H.; Ingle, David F.; Downey, Craig W.

    1988-01-01

    The use of the human steady-state evoked potential (SSEP) as a possible measure of mental-state estimation is explored. A method for evoking a visual response to a sum-of-ten sine waves is presented. This approach provides simultaneous multiple frequency measurements of the human EEG to the evoking stimulus in terms of describing functions (gain and phase) and remnant spectra. Ways in which these quantities vary with the addition of performance tasks (manual tracking, grammatical reasoning, and decision making) are presented. Models of the describing function measures can be formulated using systems engineering technology. Relationships between model parameters and performance scores during manual tracking are discussed. Problems of unresponsiveness and lack of repeatability of subject responses are addressed in terms of a need for loop closure of the SSEP. A technique to achieve loop closure using a lock-in amplifier approach is presented. Results of a study designed to test the effectiveness of using feedback to consciously connect humans to their evoked response are presented. Findings indicate that conscious control of EEG is possible. Implications of these results in terms of secondary tasks for mental-state estimation and brain actuated control are addressed.

  7. Neuroligin-1 loss is associated with reduced tenacity of excitatory synapses.

    Directory of Open Access Journals (Sweden)

    Adel Zeidan

    Full Text Available Neuroligins (Nlgns are postsynaptic, integral membrane cell adhesion molecules that play important roles in the formation, validation, and maturation of synapses in the mammalian central nervous system. Given their prominent roles in the life cycle of synapses, it might be expected that the loss of neuroligin family members would affect the stability of synaptic organization, and ultimately, affect the tenacity and persistence of individual synaptic junctions. Here we examined whether and to what extent the loss of Nlgn-1 affects the dynamics of several key synaptic molecules and the constancy of their contents at individual synapses over time. Fluorescently tagged versions of the postsynaptic scaffold molecule PSD-95, the AMPA-type glutamate receptor subunit GluA2 and the presynaptic vesicle molecule SV2A were expressed in primary cortical cultures from Nlgn-1 KO mice and wild-type (WT littermates, and live imaging was used to follow the constancy of their contents at individual synapses over periods of 8-12 hours. We found that the loss of Nlgn-1 was associated with larger fluctuations in the synaptic contents of these molecules and a poorer preservation of their contents at individual synapses. Furthermore, rates of synaptic turnover were somewhat greater in neurons from Nlgn-1 knockout mice. Finally, the increased GluA2 redistribution rates observed in neurons from Nlgn-1 knockout mice were negated by suppressing spontaneous network activity. These findings suggest that the loss of Nlgn-1 is associated with some use-dependent destabilization of excitatory synapse organization, and indicate that in the absence of Nlgn-1, the tenacity of excitatory synapses might be somewhat impaired.

  8. Layer- and Cell Type-Specific Modulation of Excitatory Neuronal Activity in the Neocortex

    Directory of Open Access Journals (Sweden)

    Gabriele Radnikow

    2018-01-01

    Full Text Available From an anatomical point of view the neocortex is subdivided into up to six layers depending on the cortical area. This subdivision has been described already by Meynert and Brodmann in the late 19/early 20. century and is mainly based on cytoarchitectonic features such as the size and location of the pyramidal cell bodies. Hence, cortical lamination is originally an anatomical concept based on the distribution of excitatory neuron. However, it has become apparent in recent years that apart from the layer-specific differences in morphological features, many functional properties of neurons are also dependent on cortical layer or cell type. Such functional differences include changes in neuronal excitability and synaptic activity by neuromodulatory transmitters. Many of these neuromodulators are released from axonal afferents from subcortical brain regions while others are released intrinsically. In this review we aim to describe layer- and cell-type specific differences in the effects of neuromodulator receptors in excitatory neurons in layers 2–6 of different cortical areas. We will focus on the neuromodulator systems using adenosine, acetylcholine, dopamine, and orexin/hypocretin as examples because these neuromodulator systems show important differences in receptor type and distribution, mode of release and functional mechanisms and effects. We try to summarize how layer- and cell type-specific neuromodulation may affect synaptic signaling in cortical microcircuits.

  9. Nicotine Receptor Subtype-Specific Effects on Auditory Evoked Oscillations and Potentials

    Science.gov (United States)

    Featherstone, Robert E.; Phillips, Jennifer M.; Thieu, Tony; Ehrlichman, Richard S.; Halene, Tobias B.; Leiser, Steven C.; Christian, Edward; Johnson, Edwin; Lerman, Caryn; Siegel, Steven J.

    2012-01-01

    Background Individuals with schizophrenia show increased smoking rates which may be due to a beneficial effect of nicotine on cognition and information processing. Decreased amplitude of the P50 and N100 auditory event-related potentials (ERPs) is observed in patients. Both measures show normalization following administration of nicotine. Recent studies identified an association between deficits in auditory evoked gamma oscillations and impaired information processing in schizophrenia, and there is evidence that nicotine normalizes gamma oscillations. Although the role of nicotine receptor subtypes in augmentation of ERPs has received some attention, less is known about how these receptor subtypes regulate the effect of nicotine on evoked gamma activity. Methodology/Principal Findings We examined the effects of nicotine, the α7 nicotine receptor antagonist methyllycaconitine (MLA) the α4β4/α4β2 nicotine receptor antagonist dihydro-beta-erythroidine (DHβE), and the α4β2 agonist AZD3480 on P20 and N40 amplitude as well as baseline and event-related gamma oscillations in mice, using electrodes in hippocampal CA3. Nicotine increased P20 amplitude, while DHβE blocked nicotine-induced enhancements in P20 amplitude. Conversely, MLA did not alter P20 amplitude either when presented alone or with nicotine. Administration of the α4β2 specific agonist AZD3480 did not alter any aspect of P20 response, suggesting that DHβE blocks the effects of nicotine through a non-α4β2 receptor specific mechanism. Nicotine and AZD3480 reduced N40 amplitude, which was blocked by both DHβE and MLA. Finally, nicotine significantly increased event-related gamma, as did AZD3480, while DHβE but not MLA blocked the effect of nicotine on event-related gamma. Conclusions/Significance These results support findings showing that nicotine-induced augmentation of P20 amplitude occurs via a DHβE sensitive mechanism, but suggests that this does not occur through activation of α4β2

  10. Elevating Endogenous GABA Levels with GAT-1 Blockade Modulates Evoked but Not Induced Responses in Human Visual Cortex

    Science.gov (United States)

    Muthukumaraswamy, Suresh D; Myers, Jim F M; Wilson, Sue J; Nutt, David J; Hamandi, Khalid; Lingford-Hughes, Anne; Singh, Krish D

    2013-01-01

    The electroencephalographic/magnetoencephalographic (EEG/MEG) signal is generated primarily by the summation of the postsynaptic currents of cortical principal cells. At a microcircuit level, these glutamatergic principal cells are reciprocally connected to GABAergic interneurons. Here we investigated the relative sensitivity of visual evoked and induced responses to altered levels of endogenous GABAergic inhibition. To do this, we pharmacologically manipulated the GABA system using tiagabine, which blocks the synaptic GABA transporter 1, and so increases endogenous GABA levels. In a single-blinded and placebo-controlled crossover study of 15 healthy participants, we administered either 15 mg of tiagabine or a placebo. We recorded whole-head MEG, while participants viewed a visual grating stimulus, before, 1, 3 and 5 h post tiagabine ingestion. Using beamformer source localization, we reconstructed responses from early visual cortices. Our results showed no change in either stimulus-induced gamma-band amplitude increases or stimulus-induced alpha amplitude decreases. However, the same data showed a 45% reduction in the evoked response component at ∼80 ms. These data demonstrate that, in early visual cortex the evoked response shows a greater sensitivity compared with induced oscillations to pharmacologically increased endogenous GABA levels. We suggest that previous studies correlating GABA concentrations as measured by magnetic resonance spectroscopy to gamma oscillation frequency may reflect underlying variations such as interneuron/inhibitory synapse density rather than functional synaptic GABA concentrations. PMID:23361120

  11. Odor-evoked inhibition of olfactory sensory neurons drives olfactory perception in Drosophila.

    Science.gov (United States)

    Cao, Li-Hui; Yang, Dong; Wu, Wei; Zeng, Xiankun; Jing, Bi-Yang; Li, Meng-Tong; Qin, Shanshan; Tang, Chao; Tu, Yuhai; Luo, Dong-Gen

    2017-11-07

    Inhibitory response occurs throughout the nervous system, including the peripheral olfactory system. While odor-evoked excitation in peripheral olfactory cells is known to encode odor information, the molecular mechanism and functional roles of odor-evoked inhibition remain largely unknown. Here, we examined Drosophila olfactory sensory neurons and found that inhibitory odors triggered outward receptor currents by reducing the constitutive activities of odorant receptors, inhibiting the basal spike firing in olfactory sensory neurons. Remarkably, this odor-evoked inhibition of olfactory sensory neurons elicited by itself a full range of olfactory behaviors from attraction to avoidance, as did odor-evoked olfactory sensory neuron excitation. These results indicated that peripheral inhibition is comparable to excitation in encoding sensory signals rather than merely regulating excitation. Furthermore, we demonstrated that a bidirectional code with both odor-evoked inhibition and excitation in single olfactory sensory neurons increases the odor-coding capacity, providing a means of efficient sensory encoding.

  12. Norepinephrine-evoked pain in fibromyalgia. A randomized pilot study [ISRCTN70707830

    Directory of Open Access Journals (Sweden)

    Casanova Jose-Miguel

    2002-01-01

    Full Text Available Abstract Background Fibromyalgia syndrome displays sympathetically maintained pain features such as frequent post-traumatic onset and stimuli-independent pain accompanied by allodynia and paresthesias. Heart rate variability studies showed that fibromyalgia patients have changes consistent with ongoing sympathetic hyperactivity. Norepinephrine-evoked pain test is used to assess sympathetically maintained pain syndromes. Our objective was to define if fibromyalgia patients have norepinephrine-evoked pain. Methods Prospective double blind controlled study. Participants: Twenty FM patients, and two age/sex matched control groups; 20 rheumatoid arthritis patients and 20 healthy controls. Ten micrograms of norepinephrine diluted in 0.1 ml of saline solution were injected in a forearm. The contrasting substance, 0.1 ml of saline solution alone, was injected in the opposite forearm. Maximum local pain elicited during the 5 minutes post-injection was graded on a visual analog scale (VAS. Norepinephrine-evoked pain was diagnosed when norepinephrine injection induced greater pain than placebo injection. Intensity of norepinephrine-evoked pain was calculated as the difference between norepinephrine minus placebo-induced VAS scores. Results Norepinephrine-evoked pain was seen in 80 % of FM patients (95% confidence intervals 56.3 – 94.3%, in 30 % of rheumatoid arthritis patients and in 30 % of healthy controls (95% confidence intervals 11.9 – 54.3 (p Conclusions Fibromyalgia patients have norepinephrine-evoked pain. This finding supports the hypothesis that fibromyalgia may be a sympathetically maintained pain syndrome.

  13. Objective correlate of subjective pain perception by contact heat-evoked potentials.

    Science.gov (United States)

    Granovsky, Yelena; Granot, Michal; Nir, Rony-Reuven; Yarnitsky, David

    2008-01-01

    The method of pain-evoked potentials has gained considerable acceptance over the last 3 decades regarding its objectivity, repeatability, and quantifiability. The present study explored whether the relationship between pain-evoked potentials and pain psychophysics obtained by contact heat stimuli is similar to those observed for the conventionally used laser stimulation. Evoked potentials (EPs) were recorded in response to contact heat stimuli at different body sites in 24 healthy volunteers. Stimuli at various temperatures were applied to the forearm (43 degrees C, 46 degrees C, 49 degrees C, and 52 degrees C) and leg (46 degrees C and 49 degrees C). The amplitudes of both components (N2 and P2) were strongly associated with the intensity of the applied stimuli and with subjective pain perception. Yet, regression analysis revealed pain perception and not stimulus intensity as the major contributing factor. A significant correlation was found between the forearm and the leg for both psychophysics and EPs amplitude. Contact heat can generate readily distinguishable evoked potentials on the scalp, consistent between upper and lower limbs. Although these potentials bear positive correlation with both stimulus intensity and pain magnitude, the latter is the main contributor to the evoked brain response.

  14. Effects of single cycle binaural beat duration on auditory evoked potentials.

    Science.gov (United States)

    Mihajloski, Todor; Bohorquez, Jorge; Özdamar, Özcan

    2014-01-01

    Binaural beat (BB) illusions are experienced as continuous central pulsations when two sounds with slightly different frequencies are delivered to each ear. It has been shown that steady-state auditory evoked potentials (AEPs) to BBs can be captured and investigated. The authors recently developed a new method of evoking transient AEPs to binaural beats using frequency modulated stimuli. This methodology was able to create single BBs in predetermined intervals with varying carrier frequencies. This study examines the effects of the BB duration and the frequency modulating component of the stimulus on the binaural beats and their evoked potentials. Normal hearing subjects were tested with a set of four durations (25, 50, 100, and 200 ms) with two stimulation configurations, binaural dichotic (binaural beats) and diotic (frequency modulation). The results obtained from the study showed that out of the given durations, the 100 ms beat, was capable of evoking the largest amplitude responses. The frequency modulation effect showed a decrease in peak amplitudes with increasing beat duration until their complete disappearance at 200 ms. Even though, at 200 ms, the frequency modulation effects were not present, the binaural beats were still perceived and captured as evoked potentials.

  15. Homeostatic regulation of excitatory synapses on striatal medium spiny neurons expressing the D2 dopamine receptor.

    Science.gov (United States)

    Thibault, Dominic; Giguère, Nicolas; Loustalot, Fabien; Bourque, Marie-Josée; Ducrot, Charles; El Mestikawy, Salah; Trudeau, Louis-Éric

    2016-05-01

    Striatal medium spiny neurons (MSNs) are contacted by glutamatergic axon terminals originating from cortex, thalamus and other regions. The striatum is also innervated by dopaminergic (DAergic) terminals, some of which release glutamate as a co-transmitter. Despite evidence for functional DA release at birth in the striatum, the role of DA in the establishment of striatal circuitry is unclear. In light of recent work suggesting activity-dependent homeostatic regulation of glutamatergic terminals on MSNs expressing the D2 DA receptor (D2-MSNs), we used primary co-cultures to test the hypothesis that stimulation of DA and glutamate receptors regulates the homeostasis of glutamatergic synapses on MSNs. Co-culture of D2-MSNs with mesencephalic DA neurons or with cortical neurons produced an increase in spines and functional glutamate synapses expressing VGLUT2 or VGLUT1, respectively. The density of VGLUT2-positive terminals was reduced by the conditional knockout of this gene from DA neurons. In the presence of both mesencephalic and cortical neurons, the density of synapses reached the same total, compatible with the possibility of a homeostatic mechanism capping excitatory synaptic density. Blockade of D2 receptors increased the density of cortical and mesencephalic glutamatergic terminals, without changing MSN spine density or mEPSC frequency. Combined blockade of AMPA and NMDA glutamate receptors increased the density of cortical terminals and decreased that of mesencephalic VGLUT2-positive terminals, with no net change in total excitatory terminal density or in mEPSC frequency. These results suggest that DA and glutamate signaling regulate excitatory inputs to striatal D2-MSNs at both the pre- and postsynaptic level, under the influence of a homeostatic mechanism controlling functional output of the circuit.

  16. Disruption of Fgf13 causes synaptic excitatory-inhibitory imbalance and genetic epilepsy and febrile seizures plus.

    Science.gov (United States)

    Puranam, Ram S; He, Xiao Ping; Yao, Lijun; Le, Tri; Jang, Wonjo; Rehder, Catherine W; Lewis, Darrell V; McNamara, James O

    2015-06-10

    We identified a family in which a translocation between chromosomes X and 14 was associated with cognitive impairment and a complex genetic disorder termed "Genetic Epilepsy and Febrile Seizures Plus" (GEFS(+)). We demonstrate that the breakpoint on the X chromosome disrupted a gene that encodes an auxiliary protein of voltage-gated Na(+) channels, fibroblast growth factor 13 (Fgf13). Female mice in which one Fgf13 allele was deleted exhibited hyperthermia-induced seizures and epilepsy. Anatomic studies revealed expression of Fgf13 mRNA in both excitatory and inhibitory neurons of hippocampus. Electrophysiological recordings revealed decreased inhibitory and increased excitatory synaptic inputs in hippocampal neurons of Fgf13 mutants. We speculate that reduced expression of Fgf13 impairs excitability of inhibitory interneurons, resulting in enhanced excitability within local circuits of hippocampus and the clinical phenotype of epilepsy. These findings reveal a novel cause of this syndrome and underscore the powerful role of FGF13 in control of neuronal excitability. Copyright © 2015 the authors 0270-6474/15/358866-16$15.00/0.

  17. Influence of visual angle on pattern reversal visual evoked potentials

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    Ruchi Kothari

    2014-01-01

    Full Text Available Purpose: The aim of this study was to find whether the visual evoked potential (VEP latencies and amplitude are altered with different visual angles in healthy adult volunteers or not and to determine the visual angle which is the optimum and most appropriate among a wide range of check sizes for the reliable interpretation of pattern reversal VEPs (PRVEPs. Materials and Methods: The present study was conducted on 40 healthy volunteers. The subjects were divided into two groups. One group consisted of 20 individuals (nine males and 11 females in the age range of 25-57 years and they were exposed to checks subtending a visual angle of 90, 120, and 180 minutes of arc. Another group comprised of 20 individuals (10 males and 10 females in the age range of 36-60 years and they were subjected to checks subtending a visual angle of 15, 30, and 120 minutes of arc. The stimulus configuration comprised of the transient pattern reversal method in which a black and white checker board is generated (full field on a VEP Monitor by an Evoked Potential Recorder (RMS EMG. EPMARK II. The statistical analysis was done by One Way Analysis of Variance (ANOVA using EPI INFO 6. Results: In Group I, the maximum (max. P100 latency of 98.8 ± 4.7 and the max. P100 amplitude of 10.05 ± 3.1 μV was obtained with checks of 90 minutes. In Group II, the max. P100 latency of 105.19 ± 4.75 msec as well as the max. P100 amplitude of 8.23 ± 3.30 μV was obtained with 15 minutes. The min. P100 latency in both the groups was obtained with checks of 120 minutes while the min. P100 amplitude was obtained with 180 minutes. A statistically significant difference was derived between means of P100 latency for 15 and 30 minutes with reference to its value for 120 minutes and between the mean value of P100 amplitude for 120 minutes and that of 90 and 180 minutes. Conclusion: Altering the size of stimulus (visual angle has an effect on the PRVEP parameters. Our study found that the 120

  18. A Telehealth System for Remote Auditory Evoked Potential Monitoring

    OpenAIRE

    Millan, Jorge; Yunda, Leonardo

    2013-01-01

    A portable, Internet-based EEG/Auditory Evoked Potential (AEP) monitoring system was developed for remote electrophysiological studies during sleep. The system records EEG/AEP simultaneously at the subject?s home for increased comfort and flexibility. The system provides simultaneous recording and remote viewing of EEG, EMG and EOG waves and allows on-line averaging of auditory evoked potentials. The design allows the recording of all major AEP components (brainstem, middle and late latency E...

  19. The Role of Odor-Evoked Memory in Psychological and Physiological Health.

    Science.gov (United States)

    Herz, Rachel S

    2016-07-19

    This article discusses the special features of odor-evoked memory and the current state-of-the-art in odor-evoked memory research to show how these unique experiences may be able to influence and benefit psychological and physiological health. A review of the literature leads to the conclusion that odors that evoke positive autobiographical memories have the potential to increase positive emotions, decrease negative mood states, disrupt cravings, and reduce physiological indices of stress, including systemic markers of inflammation. Olfactory perception factors and individual difference characteristics that would need to be considered in therapeutic applications of odor-evoked-memory are also discussed. This article illustrates how through the experimentally validated mechanisms of odor-associative learning and the privileged neuroanatomical relationship that exists between olfaction and the neural substrates of emotion, odors can be harnessed to induce emotional and physiological responses that can improve human health and wellbeing.

  20. The Role of Odor-Evoked Memory in Psychological and Physiological Health

    Directory of Open Access Journals (Sweden)

    Rachel S. Herz

    2016-07-01

    Full Text Available This article discusses the special features of odor-evoked memory and the current state-of-the-art in odor-evoked memory research to show how these unique experiences may be able to influence and benefit psychological and physiological health. A review of the literature leads to the conclusion that odors that evoke positive autobiographical memories have the potential to increase positive emotions, decrease negative mood states, disrupt cravings, and reduce physiological indices of stress, including systemic markers of inflammation. Olfactory perception factors and individual difference characteristics that would need to be considered in therapeutic applications of odor-evoked-memory are also discussed. This article illustrates how through the experimentally validated mechanisms of odor-associative learning and the privileged neuroanatomical relationship that exists between olfaction and the neural substrates of emotion, odors can be harnessed to induce emotional and physiological responses that can improve human health and wellbeing.

  1. Effects of NR1 splicing on NR1/NR3B-type excitatory glycine receptors

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    Orth Angela

    2009-04-01

    Full Text Available Abstract Background N-methyl-D-aspartate receptors (NMDARs are the most complex of ionotropic glutamate receptors (iGluRs. Subunits of this subfamily assemble into heteromers, which – depending on the subunit combination – may display very different pharmacological and electrophysiological properties. The least studied members of the NMDAR family, the NR3 subunits, have been reported to assemble with NR1 to form excitatory glycine receptors in heterologous expression systems. The heterogeneity of NMDARs in vivo is in part conferred to the receptors by splicing of the NR1 subunit, especially with regard to proton sensitivity. Results Here, we have investigated whether the NR3B subunit is capable of assembly with each of the eight functional NR1 splice variants, and whether the resulting receptors share the unique functional properties described for NR1-1a/NR3. We provide evidence that functional excitatory glycine receptors formed regardless of the NR1 isoform, and their pharmacological profile matched the one reported for NR1-1a/NR3: glycine alone fully activated the receptors, which were insensitive to glutamate and block by Mg2+. Surprisingly, amplitudes of agonist-induced currents showed little dependency on the C-terminally spliced NR1 variants in NR1/NR3B diheteromers. Even more strikingly, NR3B conferred proton sensitivity also to receptors containing NR1b variants – possibly via disturbing the "proton shield" of NR1b splice variants. Conclusion While functional assembly could be demonstrated for all combinations, not all of the specific interactions seen for NR1 isoforms with coexpressed NR2 subunits could be corroborated for NR1 assembly with NR3. Rather, NR3 abates trafficking effects mediated by the NR1 C terminus as well as the N-terminally mediated proton insensitivity. Thus, this study establishes that NR3B overrides important NR1 splice variant-specific receptor properties in NR1/NR3B excitatory glycine receptors.

  2. Thought-evoking approaches in engineering problems

    CERN Document Server

    2014-01-01

    In creating the value-added product in not distant future, it is necessary and inevitable to establish a holistic and though-evoking approach to the engineering problem, which should be at least associated with the inter-disciplinary knowledge and thought processes across the whole engineering spheres. It is furthermore desirable to integrate it with trans-disciplinary aspects ranging from manufacturing culture, through liberal-arts engineering, and industrial sociology.   The thought-evoking approach can be exemplified and typified by representative engineering problems: unveiling essential features in ‘Tangential Force Ratio and Interface Pressure’, prototype development for ‘Bio-mimetic Needle’ and application of ‘Water-jet Machining to Artificial Hip Joint’, product innovation in ‘Heat Sink for Computer’, application of ‘Graph Theory’ to similarity evaluation of production systems, leverage among reciprocity attributes in ‘Industrial and Engineering Designs for Machine Enclosure’,...

  3. Preprotachykinin A is expressed by a distinct population of excitatory neurons in the mouse superficial spinal dorsal horn including cells that respond to noxious and pruritic stimuli.

    Science.gov (United States)

    Gutierrez-Mecinas, Maria; Bell, Andrew M; Marin, Alina; Taylor, Rebecca; Boyle, Kieran A; Furuta, Takahiro; Watanabe, Masahiko; Polgár, Erika; Todd, Andrew J

    2017-03-01

    The superficial dorsal horn, which is the main target for nociceptive and pruritoceptive primary afferents, contains a high density of excitatory interneurons. Our understanding of their roles in somatosensory processing has been restricted by the difficulty of distinguishing functional populations among these cells. We recently defined 3 nonoverlapping populations among the excitatory neurons, based on the expression of neurotensin, neurokinin B, and gastrin-releasing peptide. Here we identify and characterise another population: neurons that express the tachykinin peptide substance P. We show with immunocytochemistry that its precursor protein (preprotachykinin A, PPTA) can be detected in ∼14% of lamina I-II neurons, and these are concentrated in the outer part of lamina II. Over 80% of the PPTA-positive cells lack the transcription factor Pax2 (which determines an inhibitory phenotype), and these account for ∼15% of the excitatory neurons in this region. They are different from the neurotensin, neurokinin B, or gastrin-releasing peptide neurons, although many of them contain somatostatin, which is widely expressed among superficial dorsal horn excitatory interneurons. We show that many of these cells respond to noxious thermal and mechanical stimuli and to intradermal injection of pruritogens. Finally, we demonstrate that these cells can also be identified in a knock-in Cre mouse line (Tac1), although our findings suggest that there is an additional population of neurons that transiently express PPTA. This population of substance P-expressing excitatory neurons is likely to play an important role in the transmission of signals that are perceived as pain and itch.

  4. Speech-evoked auditory brainstem responses in children with hearing loss.

    Science.gov (United States)

    Koravand, Amineh; Al Osman, Rida; Rivest, Véronique; Poulin, Catherine

    2017-08-01

    The main objective of the present study was to investigate subcortical auditory processing in children with sensorineural hearing loss. Auditory Brainstem Responses (ABRs) were recorded using click and speech/da/stimuli. Twenty-five children, aged 6-14 years old, participated in the study: 13 with normal hearing acuity and 12 with sensorineural hearing loss. No significant differences were observed for the click-evoked ABRs between normal hearing and hearing-impaired groups. For the speech-evoked ABRs, no significant differences were found for the latencies of the following responses between the two groups: onset (V and A), transition (C), one of the steady-state wave (F), and offset (O). However, the latency of the steady-state waves (D and E) was significantly longer for the hearing-impaired compared to the normal hearing group. Furthermore, the amplitude of the offset wave O and of the envelope frequency response (EFR) of the speech-evoked ABRs was significantly larger for the hearing-impaired compared to the normal hearing group. Results obtained from the speech-evoked ABRs suggest that children with a mild to moderately-severe sensorineural hearing loss have a specific pattern of subcortical auditory processing. Our results show differences for the speech-evoked ABRs in normal hearing children compared to hearing-impaired children. These results add to the body of the literature on how children with hearing loss process speech at the brainstem level. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Behavioral analyses of wind-evoked escape of the cricket, Gryllodes sigillatus.

    Science.gov (United States)

    Kanou, Masamichi; Konishi, Atsuko; Suenaga, Rie

    2006-04-01

    The wind-evoked escape behavior of the cricket Gryllodes sigillatus was investigated using an air puff stimulus. A high velocity air puff elicited the escape behavior in many crickets. The crickets tended to escape away from the stimulus source, but the direction was not accurately oriented 180 degrees from the stimulus. After bilateral cercal ablation, only a few crickets showed wind-evoked escape behavior, and their response rates did not increase even 19 days after ablation. Therefore, information on air motion detected by cercal filiform hairs is essential for triggering wind-evoked behavior. After unilateral cercal ablation, the 81.3% response rate of intact crickets decreased to 16.5%, that is, it decreased to almost 20% that of intact crickets. One week after unilateral cercal ablation, the response rate recovered to more than 60% that of intact crickets. However, the accuracy rate of the escape direction of G. sigillatus showed no change even immediately after the unilateral cercal ablation. Therefore, both cerci are not necessarily required to determine the escape direction. The behavioral characteristics of wind-evoked escape of G. sigillatus are compared with those of another species of cricket, Gryllus bimaculatus. The two species of cricket employ different strategies for wind-evoked escape.

  6. Skinfold thickness affects the isometric knee extension torque evoked by Neuromuscular Electrical Stimulation.

    Science.gov (United States)

    Medeiros, Flávia V A; Vieira, Amilton; Carregaro, Rodrigo L; Bottaro, Martim; Maffiuletti, Nicola A; Durigan, João L Q

    2015-01-01

    Subcutaneous adipose tissue may influence the transmission of electrical stimuli through to the skin, thus affecting both evoked torque and comfort perception associated with neuromuscular electrical stimulation (NMES). This could seriously affect the effectiveness of NMES for either rehabilitation or sports purposes. To investigate the effects of skinfold thickness (SFT) on maximal NMES current intensity, NMES-evoked torque, and NMES-induced discomfort. First, we compared NMES current intensity, NMES-induced discomfort, and NMES-evoked torque between two subgroups of subjects with thicker (n=10; 20.7 mm) vs. thinner (n=10; 29.4 mm) SFT. Second, we correlated SFT to NMES current intensity, NMES-induced discomfort, and NMES-evoked knee extension torque in 20 healthy women. The NMES-evoked torque was normalized to the maximal voluntary contraction (MVC) torque. The discomfort induced by NMES was assessed with a visual analog scale (VAS). NMES-evoked torque was 27.5% lower in subjects with thicker SFT (p=0.01) while maximal current intensity was 24.2% lower in subjects with thinner SFT (p=0.01). A positive correlation was found between current intensity and SFT (r=0.540, p=0.017). A negative correlation was found between NMES-evoked torque and SFT (r=-0.563, p=0.012). No significant correlation was observed between discomfort scores and SFT (rs=0.15, p=0.53). These results suggest that the amount of subcutaneous adipose tissue (as reflected by skinfold thickness) affected NMES current intensity and NMES-evoked torque, but had no effect on discomfort perception. Our findings may help physical therapists to better understand the impact of SFT on NMES and to design more rational stimulation strategies.

  7. Optogenetic stimulation of locus ceruleus neurons augments inhibitory transmission to parasympathetic cardiac vagal neurons via activation of brainstem α1 and β1 receptors.

    Science.gov (United States)

    Wang, Xin; Piñol, Ramón A; Byrne, Peter; Mendelowitz, David

    2014-04-30

    Locus ceruleus (LC) noradrenergic neurons are critical in generating alertness. In addition to inducing cortical arousal, the LC also orchestrates changes in accompanying autonomic system function that compliments increased attention, such as during stress, excitation, and/or exposure to averse or novel stimuli. Although the association between arousal and increased heart rate is well accepted, the neurobiological link between the LC and parasympathetic neurons that control heart rate has not been identified. In this study, we test directly whether activation of noradrenergic neurons in the LC influences brainstem parasympathetic cardiac vagal neurons (CVNs). CVNs were identified in transgenic mice that express channel-rhodopsin-2 (ChR2) in LC tyrosine hydroxylase neurons. Photoactivation evoked a rapid depolarization, increased firing, and excitatory inward currents in ChR2-expressing neurons in the LC. Photostimulation of LC neurons did not alter excitatory currents, but increased inhibitory neurotransmission to CVNs. Optogenetic activation of LC neurons increased the frequency of isolated glycinergic IPSCs by 27 ± 8% (p = 0.003, n = 26) and augmented GABAergic IPSCs in CVNs by 21 ± 5% (p = 0.001, n = 26). Inhibiting α1, but not α2, receptors blocked the evoked responses. Inhibiting β1 receptors prevented the increase in glycinergic, but not GABAergic, IPSCs in CVNs. This study demonstrates LC noradrenergic neurons inhibit the brainstem CVNs that generate parasympathetic activity to the heart. This inhibition of CVNs would increase heart rate and risks associated with tachycardia. The receptors activated within this pathway, α1 and/or β1 receptors, are targets for clinically prescribed antagonists that promote slower, cardioprotective heart rates during heightened vigilant states.

  8. Sex-specific automatic responses to infant cries: TMS reveals greater excitability in females than males in motor evoked potentials

    Directory of Open Access Journals (Sweden)

    Irene eMessina

    2016-01-01

    Full Text Available Neuroimaging reveals that infant cries activate parts of the premotor cortical system. To validate this effect in a more direct way, we used event-related transcranial magnetic stimulation (TMS. Here, we investigated the presence and the time course of modulation of motor cortex excitability in young adults who listened to infant cries. Specifically, we recorded motor evoked potentials (MEPs from the biceps brachii (BB and interosseus dorsalis primus (ID1 muscles as produced by TMS delivered from 0 to 250 ms from sound onset in six steps of 50 ms in 10 females and 10 males. We observed an excitatory modulation of MEPs at 100 ms from the onset of the infant cry specific to females and to the ID1 muscle. We regard this modulation as a response to natural cry sounds because it was delayed, attenuated to stimuli increasingly different from natural cry, and was absent in a separate group of females who listened to non-cry stimuli physically matched to natural infant cries. Furthermore, the 100-ms latency of this modulation is not compatible with a voluntary reaction to the stimulus but suggests an automatic, bottom-up audiomotor association. The brains of adult females appear to be tuned to respond to infant cries with automatic motor excitation. This effect may reflect the greater and longstanding burden on females in caregiving infants.

  9. Effects of sarcosine and N, N-dimethylglycine on NMDA receptor-mediated excitatory field potentials.

    Science.gov (United States)

    Lee, Mei-Yi; Lin, Yi-Ruu; Tu, Yi-Shu; Tseng, Yufeng Jane; Chan, Ming-Huan; Chen, Hwei-Hsien

    2017-02-28

    Sarcosine, a glycine transporter type 1 inhibitor and an N-methyl-D-aspartate (NMDA) receptor co-agonist at the glycine binding site, potentiates NMDA receptor function. Structurally similar to sarcosine, N,N-dimethylglycine (DMG) is also N-methyl glycine-derivative amino acid and commonly used as a dietary supplement. The present study compared the effects of sarcosine and DMG on NMDA receptor-mediated excitatory field potentials (EFPs) in mouse medial prefrontal cortex brain slices using a multi-electrode array system. Glycine, sarcosine and DMG alone did not alter the NMDA receptor-mediated EFPs, but in combination with glutamate, glycine and its N-methyl derivatives significantly increased the frequency and amplitude of EFPs. The enhancing effects of glycine analogs in combination with glutamate on EFPs were remarkably reduced by the glycine binding site antagonist 7-chlorokynurenate (7-CK). However, DMG, but not sarcosine, reduced the frequency and amplitude of EFPs elicited by co-application of glutamate plus glycine. D-cycloserine, a partial agonist at the glycine binding site on NMDA receptors, affected EFPs in a similar manner to DMG. Furthermore, DMG, but not sarcosine, reduced the frequencies and amplitudes of EFPs elicited by glutamate plus D-serine, another endogenous ligand for glycine binding site. These findings suggest that sarcosine acts as a full agonist, yet DMG is a partial agonist at glycine binding site of NMDA receptors. The molecular docking analysis indicated that the interactions of glycine, sarcosine, and DMG to NMDA receptors are highly similar, supporting that the glycine binding site of NMDA receptors is a critical target site for sarcosine and DMG.

  10. Pharmacology of Bradykinin-Evoked Coughing in Guinea Pigs.

    Science.gov (United States)

    Hewitt, Matthew M; Adams, Gregory; Mazzone, Stuart B; Mori, Nanako; Yu, Li; Canning, Brendan J

    2016-06-01

    Bradykinin has been implicated as a mediator of the acute pathophysiological and inflammatory consequences of respiratory tract infections and in exacerbations of chronic diseases such as asthma. Bradykinin may also be a trigger for the coughing associated with these and other conditions. We have thus set out to evaluate the pharmacology of bradykinin-evoked coughing in guinea pigs. When inhaled, bradykinin induced paroxysmal coughing that was abolished by the bradykinin B2 receptor antagonist HOE 140. These cough responses rapidly desensitized, consistent with reports of B2 receptor desensitization. Bradykinin-evoked cough was potentiated by inhibition of both neutral endopeptidase and angiotensin-converting enzyme (with thiorphan and captopril, respectively), but was largely unaffected by muscarinic or thromboxane receptor blockade (atropine and ICI 192605), cyclooxygenase, or nitric oxide synthase inhibition (meclofenamic acid and N(G)-nitro-L-arginine). Calcium influx studies in bronchopulmonary vagal afferent neurons dissociated from vagal sensory ganglia indicated that the tachykinin-containing C-fibers arising from the jugular ganglia mediate bradykinin-evoked coughing. Also implicating the jugular C-fibers was the observation that simultaneous blockade of neurokinin2 (NK2; SR48968) and NK3 (SR142801 or SB223412) receptors nearly abolished the bradykinin-evoked cough responses. The data suggest that bradykinin induces coughing in guinea pigs by activating B2 receptors on bronchopulmonary C-fibers. We speculate that therapeutics targeting the actions of bradykinin may prove useful in the treatment of cough. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  11. Do video games evoke specific types of epileptic seizures?

    Science.gov (United States)

    Piccioli, Marta; Vigevano, Federico; Buttinelli, Carla; Kasteleijn-Nolst Trenité, Dorothée G A

    2005-11-01

    We determined whether epileptic clinical manifestations evoked by playing video games (VG) differ from those evoked by intermittent photic stimulation (IPS) or striped patterns (P). We exposed nine children who had TV- and VG-evoked seizures in daily life to 12 VG after standardized photic stimulation and pattern stimulation. Their EEGs were recorded continuously, analyzed, and then correlated with a video of their behavior. Similar types of clinical signs were seen during VG, P, and IPS, but the signs we observed were more subtle during the VG. Eight patients showed a clear lateralization. A new observation was the lowering of the eyelids to a state of half-closed. Our study suggests that the type of visual stimulus provoking a photoparoxysmal response or seizure is not particularly relevant. The children belonged to different epilepsy groups, and our findings add to the discussion on the boundaries of the epilepsy types.

  12. Awareness during anaesthesia for surgery requiring evoked potential monitoring: A pilot study

    Directory of Open Access Journals (Sweden)

    Pritish J Korula

    2017-01-01

    Full Text Available Background: Evoked potential monitoring such as somatosensory-evoked potential (SSEP or motor-evoked potential (MEP monitoring during surgical procedures in proximity to the spinal cord requires minimising the minimum alveolar concentrations (MACs below the anaesthetic concentrations normally required (1 MAC to prevent interference in amplitude and latency of evoked potentials. This could result in awareness. Our primary objective was to determine the incidence of awareness while administering low MAC inhalational anaesthetics for these unique procedures. The secondary objective was to assess the adequacy of our anaesthetic technique from neurophysiologist′s perspective. Methods: In this prospective observational pilot study, 61 American Society of Anesthesiologists 1 and 2 patients undergoing spinal surgery for whom intraoperative evoked potential monitoring was performed were included; during the maintenance phase, 0.7-0.8 MAC of isoflurane was targeted. We evaluated the intraoperative depth of anaesthesia using a bispectral (BIS index monitor as well as the patients response to surgical stimulus (PRST scoring system. Post-operatively, a modified Bruce questionnaire was used to verify awareness. The adequacy of evoked potential readings was also assessed. Results: Of the 61 patients, no patient had explicit awareness. Intraoperatively, 19 of 61 patients had a BIS value of above sixty at least once, during surgery. There was no correlation with PRST scoring and BIS during surgery. Fifty-four out of 61 patient′s evoked potential readings were deemed ′good′ or ′fair′ for the conduct of electrophysiological monitoring. Conclusions: This pilot study demonstrates that administering low MAC inhalational anaesthetics to facilitate evoked potential monitoring does not result in explicit awareness. However, larger studies are needed to verify this. The conduct of SSEP electrophysiological monitoring was satisfactory with the use of this

  13. Transmitter modulation of spike-evoked calcium transients in arousal related neurons

    DEFF Research Database (Denmark)

    Kohlmeier, Kristi Anne; Leonard, Christopher S

    2006-01-01

    Nitric oxide synthase (NOS)-containing cholinergic neurons in the laterodorsal tegmentum (LDT) influence behavioral and motivational states through their projections to the thalamus, ventral tegmental area and a brainstem 'rapid eye movement (REM)-induction' site. Action potential-evoked intracel......Nitric oxide synthase (NOS)-containing cholinergic neurons in the laterodorsal tegmentum (LDT) influence behavioral and motivational states through their projections to the thalamus, ventral tegmental area and a brainstem 'rapid eye movement (REM)-induction' site. Action potential......-evoked intracellular calcium transients dampen excitability and stimulate NO production in these neurons. In this study, we investigated the action of several arousal-related neurotransmitters and the role of specific calcium channels in these LDT Ca(2+)-transients by simultaneous whole-cell recording and calcium...... of cholinergic LDT neurons and that inhibition of spike-evoked Ca(2+)-transients is a common action of neurotransmitters that also activate GIRK channels in these neurons. Because spike-evoked calcium influx dampens excitability, our findings suggest that these 'inhibitory' transmitters could boost firing rate...

  14. Early life vincristine exposure evokes mechanical pain hypersensitivity in the developing rat.

    Science.gov (United States)

    Schappacher, Katie A; Styczynski, Lauren; Baccei, Mark L

    2017-09-01

    Vincristine (VNC) is commonly used to treat pediatric cancers, including the most prevalent childhood malignancy, acute lymphoblastic leukemia. Although clinical evidence suggests that VNC causes peripheral neuropathy in children, the degree to which pediatric chemotherapeutic regimens influence pain sensitivity throughout life remains unclear, in part because of the lack of an established animal model of chemotherapy-induced neuropathic pain during early life. Therefore, this study investigated the effects of VNC exposure between postnatal days (P) 11 and 21 on mechanical and thermal pain sensitivity in the developing rat. Low doses of VNC (15 or 30 μg/kg) failed to alter nociceptive withdrawal reflexes at any age examined compared with vehicle-injected littermate controls. Meanwhile, high dose VNC (60 μg/kg) evoked mechanical hypersensitivity in both sexes beginning at P26 that persisted until adulthood and included both static and dynamic mechanical allodynia. Hind paw withdrawal latencies to noxious heat and cold were unaffected by high doses of VNC, suggesting a selective effect of neonatal VNC on mechanical pain sensitivity. Gross and fine motor function appeared normal after VNC treatment, although a small decrease in weight gain was observed. The VNC regimen also produced a significant decrease in intraepidermal nerve fiber density in the hind paw skin by P33. Overall, the present results demonstrate that high-dose administration of VNC during the early postnatal period selectively evokes a mechanical hypersensitivity that is slow to emerge during adolescence, providing further evidence that aberrant sensory input during early life can have prolonged consequences for pain processing.

  15. [Evoked potentials N200/P300 disorders and clinical phenotype in Cuban families with paranoid schizophrenia: a family-based association study].

    Science.gov (United States)

    Guerra López, Seidel; Martín Reyes, Migdyrai; Pedroso Rodríguez, María de Los Ángeles; Reyes Berazain, Adnelys; Mendoza Quiñones, Raúl; Bravo Collazo, Tania Martha; Días de Villarvilla, Thais; Machado Cano, María Julia; Bobés León, María Antonieta

    2015-04-01

    N200 and P300 event-related evoked potentials provide sensitive measurements of sensory and cognitive function and have been used to study information processing in patients with schizophrenia and their unaffected first-degree relatives. Reduced amplitude and increased latency of N200 and P300 potentials have been consistently reported in schizophrenia. Thus, event-related evoked potentials abnormalities are promising possible biological markers for genetic vulnerability to schizophrenia. To assess the association of changes in latency, amplitude and topographic distribution of potentials N200 and P300 of patients with paranoid schizophrenia and their healthy first-degree relatives, in families with schizophrenia multiplex. We measured latency and amplitude of the N200 and P300 component of evoked potentials using an auditory odd-ball paradigm in 25 schizophrenic patients (probands) from 60 families multiply affected with paranoid schizophrenia, 23 of their non-schizophrenic first-degree relatives and 25 unrelated healthy controls, through a study of family association. Schizophrenic patients and their relatives showed significant latency prolongation and amplitude reduction of the N200 and P300 waves compared to controls. Left-temporal as compared to right-temporal N200 and P300 were significantly smaller in schizophrenic patients and their non-schizophrenic first-degree relatives than in controls. Our results suggest that event-related evoked potentials abnormalities may serve as markers of genetic vulnerability in schizophrenia. Confirming results of other researchers, this present study suggests that latency prolongation and amplitude reduction of the N200 and P300 waves and an altered topography at temporal sites may be a trait “marker” of paranoid schizophrenia.

  16. Do Puzzle Pieces and Autism Puzzle Piece Logos Evoke Negative Associations?

    Science.gov (United States)

    Gernsbacher, Morton Ann; Raimond, Adam R.; Stevenson, Jennifer L.; Boston, Jilana S.; Harp, Bev

    2018-01-01

    Puzzle pieces have become ubiquitous symbols for autism. However, puzzle-piece imagery stirs debate between those who support and those who object to its use because they believe puzzle-piece imagery evokes negative associations. Our study empirically investigated whether puzzle pieces evoke negative associations in the general public.…

  17. Connectopathy in Autism Spectrum Disorders: A Review of Evidence from Visual Evoked Potentials and Diffusion Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Takao Yamasaki

    2017-11-01

    Full Text Available Individuals with autism spectrum disorder (ASD show superior performance in processing fine details; however, they often exhibit impairments of gestalt face, global motion perception, and visual attention as well as core social deficits. Increasing evidence has suggested that social deficits in ASD arise from abnormal functional and structural connectivities between and within distributed cortical networks that are recruited during social information processing. Because the human visual system is characterized by a set of parallel, hierarchical, multistage network systems, we hypothesized that the altered connectivity of visual networks contributes to social cognition impairment in ASD. In the present review, we focused on studies of altered connectivity of visual and attention networks in ASD using visual evoked potentials (VEPs, event-related potentials (ERPs, and diffusion tensor imaging (DTI. A series of VEP, ERP, and DTI studies conducted in our laboratory have demonstrated complex alterations (impairment and enhancement of visual and attention networks in ASD. Recent data have suggested that the atypical visual perception observed in ASD is caused by altered connectivity within parallel visual pathways and attention networks, thereby contributing to the impaired social communication observed in ASD. Therefore, we conclude that the underlying pathophysiological mechanism of ASD constitutes a “connectopathy.”

  18. Biochemistry of an olfactory purinergic system: dephosphorylation of excitatory nucleotides and uptake of adenosine

    Energy Technology Data Exchange (ETDEWEB)

    Trapido-Rosenthal, H G; Carr, W E; Gleeson, R A

    1987-10-01

    The olfactory organ of the spiny lobster, Panulirus argus, is composed of chemosensory sensilla containing the dendrites of primary chemosensory neurons. Receptors on these dendrites are activated by the nucleotides AMP, ADP, and ATP but not by the nucleoside adenosine. It is shown here that the lobster chemosensory sensilla contain enzymes that dephosphorylate excitatory nucleotides and an uptake system that internalizes the nonexcitatory dephosphorylated product adenosine. The uptake of (/sup 3/H)-adenosine is saturable with increasing concentration, linear with time for up to 3 h, sodium dependent, insensitive to moderate pH changes and has a Km of 7.1 microM and a Vmax of 5.2 fmol/sensillum/min (573 fmol/micrograms of protein/min). Double-label experiments show that sensilla dephosphorylate nucleotides extracellularly; /sup 3/H from adenine-labeled AMP or ATP is internalized, whereas 32P from phosphate-labeled nucleotides is not. The dephosphorylation of AMP is very rapid; /sup 3/H from AMP is internalized at the same rate as /sup 3/H from adenosine. Sensillar 5'-ectonucleotidase activity is inhibited by ADP and the ADP analog alpha, beta-methylene ADP. Collectively, these results indicate that the enzymes and the uptake system whereby chemosensory sensilla of the lobster inactivate excitatory nucleotides and clear adenosine from extracellular spaces are very similar to those present in the internal tissues of vertebrates, where nucleotides have many neuroactive effects.

  19. Robust working memory in an asynchronously spiking neural network realized in neuromorphic VLSI

    Directory of Open Access Journals (Sweden)

    Massimiliano eGiulioni

    2012-02-01

    Full Text Available We demonstrate bistable attractor dynamics in a spiking neural network implemented with neuromorphic VLSI hardware. The on-chip network consists of three interacting populations (two excitatory, one inhibitory of integrate-and-fire (LIF neurons. One excitatory population is distinguished by strong synaptic self-excitation, which sustains meta-stable states of ‘high’ and ‘low’-firing activity. Depending on the overall excitability, transitions to the ‘high’ state may be evoked by external stimulation, or may occur spontaneously due to random activity fluctuations. In the former case, the ‘high’ state retains a working memory of a stimulus until well after its release. In the latter case, ‘high’ states remain stable for seconds, three orders of magnitude longer than the largest time-scale implemented in the circuitry. Evoked and spontaneous transitions form a continuum and may exhibit a wide range of latencies, depending on the strength of external stimulation and of recurrent synaptic excitation. In addition, we investigated corrupted ‘high’ states comprising neurons of both excitatory populations. Within a basin of attraction, the network dynamics corrects such states and re-establishes the prototypical ‘high’ state. We conclude that, with effective theoretical guidance, full-fledged attractor dynamics can be realized with comparatively small populations of neuromorphic hardware neurons.

  20. Robust Working Memory in an Asynchronously Spiking Neural Network Realized with Neuromorphic VLSI.

    Science.gov (United States)

    Giulioni, Massimiliano; Camilleri, Patrick; Mattia, Maurizio; Dante, Vittorio; Braun, Jochen; Del Giudice, Paolo

    2011-01-01

    We demonstrate bistable attractor dynamics in a spiking neural network implemented with neuromorphic VLSI hardware. The on-chip network consists of three interacting populations (two excitatory, one inhibitory) of leaky integrate-and-fire (LIF) neurons. One excitatory population is distinguished by strong synaptic self-excitation, which sustains meta-stable states of "high" and "low"-firing activity. Depending on the overall excitability, transitions to the "high" state may be evoked by external stimulation, or may occur spontaneously due to random activity fluctuations. In the former case, the "high" state retains a "working memory" of a stimulus until well after its release. In the latter case, "high" states remain stable for seconds, three orders of magnitude longer than the largest time-scale implemented in the circuitry. Evoked and spontaneous transitions form a continuum and may exhibit a wide range of latencies, depending on the strength of external stimulation and of recurrent synaptic excitation. In addition, we investigated "corrupted" "high" states comprising neurons of both excitatory populations. Within a "basin of attraction," the network dynamics "corrects" such states and re-establishes the prototypical "high" state. We conclude that, with effective theoretical guidance, full-fledged attractor dynamics can be realized with comparatively small populations of neuromorphic hardware neurons.

  1. Heat pulse excitability of vestibular hair cells and afferent neurons

    Science.gov (United States)

    Brichta, Alan M.; Tabatabaee, Hessam; Boutros, Peter J.; Ahn, JoongHo; Della Santina, Charles C.; Poppi, Lauren A.; Lim, Rebecca

    2016-01-01

    In the present study we combined electrophysiology with optical heat pulse stimuli to examine thermodynamics of membrane electrical excitability in mammalian vestibular hair cells and afferent neurons. We recorded whole cell currents in mammalian type II vestibular hair cells using an excised preparation (mouse) and action potentials (APs) in afferent neurons in vivo (chinchilla) in response to optical heat pulses applied to the crista (ΔT ≈ 0.25°C per pulse). Afferent spike trains evoked by heat pulse stimuli were diverse and included asynchronous inhibition, asynchronous excitation, and/or phase-locked APs synchronized to each infrared heat pulse. Thermal responses of membrane currents responsible for APs in ganglion neurons were strictly excitatory, with Q10 ≈ 2. In contrast, hair cells responded with a mix of excitatory and inhibitory currents. Excitatory hair cell membrane currents included a thermoelectric capacitive current proportional to the rate of temperature rise (dT/dt) and an inward conduction current driven by ΔT. An iberiotoxin-sensitive inhibitory conduction current was also evoked by ΔT, rising in heat pulse excitability in vestibular sensory organs and provide quantitative methods for rational application of optical heat pulses to examine protein biophysics and manipulate cellular excitability. PMID:27226448

  2. Refractory episodic vertigo: role of intratympanic gentamicin and vestibular evoked myogenic potentials,

    Directory of Open Access Journals (Sweden)

    Erika Celis-Aguilar

    Full Text Available Abstract Introduction: Even today, the treatment of intractable vertigo remains a challenge. Vestibular ablation with intratympanic gentamicin stands as a good alternative in the management of refractory vertigo patients. Objective: To control intractable vertigo through complete saccular and horizontal canal vestibular ablation with intratympanic gentamicin treatment. Methods: Patients with refractory episodic vertigo were included. The inclusion criteria were: unilateral ear disease, moderate to profound sensorineural hearing loss, and failure to other treatments. Included patients underwent 0.5-0.8 mL of gentamicin intratympanic application at a 30 mg/mL concentration. Vestibular ablation was confirmed by the absence of response on cervical vestibular evoked myogenic potentials and no response on caloric tests. Audiometry, electronystagmography with iced water, and vestibular evoked myogenic potentials were performed in all patients. Results: Ten patients were included; nine patients with Meniere's disease and one patient with (late onset delayed hydrops. Nine patients showed an absent response on vestibular evoked myogenic potentials and no response on caloric tests. The only patient with low amplitude on cervical vestibular evoked myogenic potentials had vertigo recurrence. Vertigo control was achieved in 90% of the patients. One patient developed hearing loss >30 dB. Conclusions: Cervical vestibular evoked myogenic potentials confirmed vestibular ablation in patients treated with intratympanic gentamicin. High-grade vertigo control was due to complete saccular and horizontal canal ablation (no response to iced water in electronystagmography and no response on cervical vestibular evoked myogenic potentials.

  3. Phantom somatosensory evoked potentials following selective intraneural electrical stimulation in two amputees.

    Science.gov (United States)

    Granata, Giuseppe; Di Iorio, Riccardo; Romanello, Roberto; Iodice, Francesco; Raspopovic, Stanisa; Petrini, Francesco; Strauss, Ivo; Valle, Giacomo; Stieglitz, Thomas; Čvančara, Paul; Andreu, David; Divoux, Jean-Louis; Guiraud, David; Wauters, Loic; Hiairrassary, Arthur; Jensen, Winnie; Micera, Silvestro; Rossini, Paolo Maria

    2018-06-01

    The aim of the paper is to objectively demonstrate that amputees implanted with intraneural interfaces are truly able to feel a sensation in the phantom hand by recording "phantom" somatosensory evoked potentials from the corresponding brain areas. We implanted four transverse intrafascicular multichannel electrodes, available with percutaneous connections to a multichannel electrical stimulator, in the median and ulnar nerves of two left trans-radial amputees. Two channels of the implants that were able to elicit sensations during intraneural nerve stimulation were chosen, in both patients, for recording somatosensory evoked potentials. We recorded reproducible evoked responses by stimulating the median and the ulnar nerves in both cases. Latencies were in accordance with the arrival of somatosensory information to the primary somatosensory cortex. Our results provide evidence that sensations generated by intraneural stimulation are truly perceived by amputees and located in the phantom hand. Moreover, our results strongly suggest that sensations perceived in different parts of the phantom hand result in different evoked responses. Somatosensory evoked potentials obtained by selective intraneural electrical stimulation in amputee patients are a useful tool to provide an objective demonstration of somatosensory feedback in new generation bidirectional prostheses. Copyright © 2018. Published by Elsevier B.V.

  4. An inventory and update of jealousy-evoking partner behaviours in modern society.

    Science.gov (United States)

    Dijkstra, Pieternel; Barelds, Dick P H; Groothof, Hinke A K

    2010-01-01

    The goal of the present study was to identify the most important jealousy-evoking partner behaviours and to examine the extent to which these behaviours evoke jealousy. Based on the literature, a questionnaire was constructed containing 42 jealousy-evoking partner behaviours, including a partner's extra-dyadic involvement with someone else by means of modern communication devices, such as the Internet. A second study examined the extent to which undergraduates and a community sample experienced jealousy in response to these partner behaviours. Results showed that explicit unfaithful behaviours evoked most feelings of jealousy, followed by a partner's emotional or romantic involvement with someone else by means of modern communication devices. In general, older individuals responded with less jealousy in response to a partner's unfaithful and suspicious behaviours. Clinical implications are discussed. (c) 2009 John Wiley & Sons, Ltd.

  5. Evoked Brain Activity and Personnel Performance

    Science.gov (United States)

    1987-10-01

    Shucard and Horn (1972), Galbraith, Gliddon, and Busk (1970), and Callaway (1975), the latter using Navy recruits. Callaway’s own work was reported at...G.C., Gliddon, J.B., & Busk , J. (1970). Visual evoked responses in mentally retarded and nonretarded subjects. American Journal of Mental Deficiency

  6. Cell-specific gain modulation by synaptically released zinc in cortical circuits of audition.

    Science.gov (United States)

    Anderson, Charles T; Kumar, Manoj; Xiong, Shanshan; Tzounopoulos, Thanos

    2017-09-09

    In many excitatory synapses, mobile zinc is found within glutamatergic vesicles and is coreleased with glutamate. Ex vivo studies established that synaptically released (synaptic) zinc inhibits excitatory neurotransmission at lower frequencies of synaptic activity but enhances steady state synaptic responses during higher frequencies of activity. However, it remains unknown how synaptic zinc affects neuronal processing in vivo. Here, we imaged the sound-evoked neuronal activity of the primary auditory cortex in awake mice. We discovered that synaptic zinc enhanced the gain of sound-evoked responses in CaMKII-expressing principal neurons, but it reduced the gain of parvalbumin- and somatostatin-expressing interneurons. This modulation was sound intensity-dependent and, in part, NMDA receptor-independent. By establishing a previously unknown link between synaptic zinc and gain control of auditory cortical processing, our findings advance understanding about cortical synaptic mechanisms and create a new framework for approaching and interpreting the role of the auditory cortex in sound processing.

  7. Laser-evoked coloration in polymers

    International Nuclear Information System (INIS)

    Zheng, H.Y.; Rosseinsky, David; Lim, G.C.

    2005-01-01

    Laser-evoked coloration in polymers has long been a major aim of polymer technology for potential applications in product surface decoration, marking personalised images and logos. However, the coloration results reported so far were mostly attributed to laser-induced thermal-chemical reactions. The laser-irradiated areas are characterized with grooves due to material removal. Furthermore, only single color was laser-induced in any given polymer matrix. To induce multiple colors in a given polymer matrix with no apparent surface material removal is most desirable and challenging and may be achieved through laser-induced photo-chemical reactions. However, little public information is available at present. We report that two colors of red and green have been produced on an initially transparent CPV/PVA samples through UV laser-induced photo-chemical reactions. This is believed the first observation of laser-induced multiple-colors in the given polymer matrix. It is believed that the colorants underwent photo-effected electron transfer with suitable electron donors from the polymers to change from colorless bipyridilium Bipm 2+ to the colored Bipm + species. The discovery may lead to new approaches to the development of laser-evoked multiple coloration in polymers

  8. Rapid and Objective Assessment of Neural Function in Autism Spectrum Disorder Using Transient Visual Evoked Potentials.

    Directory of Open Access Journals (Sweden)

    Paige M Siper

    Full Text Available There is a critical need to identify biomarkers and objective outcome measures that can be used to understand underlying neural mechanisms in autism spectrum disorder (ASD. Visual evoked potentials (VEPs offer a noninvasive technique to evaluate the functional integrity of neural mechanisms, specifically visual pathways, while probing for disease pathophysiology.Transient VEPs (tVEPs were obtained from 96 unmedicated children, including 37 children with ASD, 36 typically developing (TD children, and 23 unaffected siblings (SIBS. A conventional contrast-reversing checkerboard condition was compared to a novel short-duration condition, which was developed to enable objective data collection from severely affected populations who are often excluded from electroencephalographic (EEG studies.Children with ASD showed significantly smaller amplitudes compared to TD children at two of the earliest critical VEP components, P60-N75 and N75-P100. SIBS showed intermediate responses relative to ASD and TD groups. There were no group differences in response latency. Frequency band analyses indicated significantly weaker responses for the ASD group in bands encompassing gamma-wave activity. Ninety-two percent of children with ASD were able to complete the short-duration condition compared to 68% for the standard condition.The current study establishes the utility of a short-duration tVEP test for use in children at varying levels of functioning and describes neural abnormalities in children with idiopathic ASD. Implications for excitatory/inhibitory balance as well as the potential application of VEP for use in clinical trials are discussed.

  9. Brain-stem evoked potentials and noise effects in seagulls.

    Science.gov (United States)

    Counter, S A

    1985-01-01

    Brain-stem auditory evoked potentials (BAEP) recorded from the seagull were large-amplitude, short-latency, vertex-positive deflections which originate in the eighth nerve and several brain-stem nuclei. BAEP waveforms were similar in latency and configurations to that reported for certain other lower vertebrates and some mammals. BAEP recorded at several pure tone frequencies throughout the seagull's auditory spectrum showed an area of heightened auditory sensitivity between 1 and 3 kHz. This range was also found to be the primary bandwidth of the vocalization output of young seagulls. Masking by white noise and pure tones had remarkable effects on several parameters of the BAEP. In general, the tone- and click-induced BAEP were either reduced or obliterated by both pure tone and white noise maskers of specific signal to noise ratios and high intensity levels. The masking effects observed in this study may be related to the manner in which seagulls respond to intense environmental noise. One possible conclusion is that intense environmental noise, such as aircraft engine noise, may severely alter the seagull's localization apparatus and induce sonogenic stress, both of which could cause collisions with low-flying aircraft.

  10. Contribution of presynaptic HCN channels to excitatory inputs of spinal substantia gelatinosa neurons.

    Science.gov (United States)

    Peng, S-C; Wu, J; Zhang, D-Y; Jiang, C-Y; Xie, C-N; Liu, T

    2017-09-01

    Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are pathological pain-associated voltage-gated ion channels. They are widely expressed in central nervous system including spinal lamina II (also named the substantia gelatinosa, SG). Here, we examined the distribution of HCN channels in glutamatergic synaptic terminals as well as their role in the modulation of synaptic transmission in SG neurons from SD rats and glutamic acid decarboxylase-67 (GAD67)-GFP mice. We found that the expression of the HCN channel isoforms was varied in SG. The HCN4 isoform showed the highest level of co-localization with VGLUT2 (23±3%). In 53% (n=21/40 neurons) of the SG neurons examined in SD rats, application of HCN channel blocker, ZD7288 (10μM), decreased the frequency of spontaneous (s) and miniature (m) excitatory postsynaptic currents (EPSCs) by 37±4% and 33±4%, respectively. Consistently, forskolin (FSK) (an activator of adenylate cyclase) significantly increased the frequency of mEPSCs by 225±34%, which could be partially inhibited by ZD7288. Interestingly, the effects of ZD7288 and FSK on sEPSC frequency were replicated in non-GFP-expressing neurons, but not in GFP-expressing GABAergic SG neurons, in GAD67-GFP transgenic C57/BL6 mice. In summary, our results represent a previously unknown cellular mechanism by which presynaptic HCN channels, especially HCN4, regulate the glutamate release from presynaptic terminals that target excitatory, but not inhibitory SG interneurons. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. Refractory episodic vertigo: role of intratympanic gentamicin and vestibular evoked myogenic potentials.

    Science.gov (United States)

    Celis-Aguilar, Erika; Hinojosa-González, Ramon; Vales-Hidalgo, Olivia; Coutinho-Toledo, Heloisa

    Even today, the treatment of intractable vertigo remains a challenge. Vestibular ablation with intratympanic gentamicin stands as a good alternative in the management of refractory vertigo patients. To control intractable vertigo through complete saccular and horizontal canal vestibular ablation with intratympanic gentamicin treatment. Patients with refractory episodic vertigo were included. The inclusion criteria were: unilateral ear disease, moderate to profound sensorineural hearing loss, and failure to other treatments. Included patients underwent 0.5-0.8mL of gentamicin intratympanic application at a 30mg/mL concentration. Vestibular ablation was confirmed by the absence of response on cervical vestibular evoked myogenic potentials and no response on caloric tests. Audiometry, electronystagmography with iced water, and vestibular evoked myogenic potentials were performed in all patients. Ten patients were included; nine patients with Meniere's disease and one patient with (late onset) delayed hydrops. Nine patients showed an absent response on vestibular evoked myogenic potentials and no response on caloric tests. The only patient with low amplitude on cervical vestibular evoked myogenic potentials had vertigo recurrence. Vertigo control was achieved in 90% of the patients. One patient developed hearing loss >30dB. Cervical vestibular evoked myogenic potentials confirmed vestibular ablation in patients treated with intratympanic gentamicin. High-grade vertigo control was due to complete saccular and horizontal canal ablation (no response to iced water in electronystagmography and no response on cervical vestibular evoked myogenic potentials). Copyright © 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  12. A comparison of auditory evoked potentials to acoustic beats and to binaural beats.

    Science.gov (United States)

    Pratt, Hillel; Starr, Arnold; Michalewski, Henry J; Dimitrijevic, Andrew; Bleich, Naomi; Mittelman, Nomi

    2010-04-01

    The purpose of this study was to compare cortical brain responses evoked by amplitude modulated acoustic beats of 3 and 6 Hz in tones of 250 and 1000 Hz with those evoked by their binaural beats counterparts in unmodulated tones to indicate whether the cortical processes involved differ. Event-related potentials (ERPs) were recorded to 3- and 6-Hz acoustic and binaural beats in 2000 ms duration 250 and 1000 Hz tones presented with approximately 1 s intervals. Latency, amplitude and source current density estimates of ERP components to beats-evoked oscillations were determined and compared across beat types, beat frequencies and base (carrier) frequencies. All stimuli evoked tone-onset components followed by oscillations corresponding to the beat frequency, and a subsequent tone-offset complex. Beats-evoked oscillations were higher in amplitude in response to acoustic than to binaural beats, to 250 than to 1000 Hz base frequency and to 3 Hz than to 6 Hz beat frequency. Sources of the beats-evoked oscillations across all stimulus conditions located mostly to left temporal lobe areas. Differences between estimated sources of potentials to acoustic and binaural beats were not significant. The perceptions of binaural beats involve cortical activity that is not different than acoustic beats in distribution and in the effects of beat- and base frequency, indicating similar cortical processing. Copyright 2010 Elsevier B.V. All rights reserved.

  13. Saccadic Alterations in Severe Developmental Dyslexia

    Directory of Open Access Journals (Sweden)

    Stefano Pensiero

    2013-01-01

    Full Text Available It is not sure if persons with dyslexia have ocular motor deficits in addition to their deficits in rapid visual information processing. A 15-year-old boy afflicted by severe dyslexia was submitted to saccadic eye movement recording. Neurological and ophthalmic examinations were normal apart from the presence of an esophoria for near and slightly longer latencies of pattern visual evoked potentials. Subclinical saccadic alterations were present, which could be at the basis of the reading pathology: (1 low velocities (and larger durations of the adducting saccades of the left eye with undershooting and long-lasting postsaccadic onward drift, typical of the internuclear ophthalmoplegia; (2 saccades interrupted in mid-flight and fixation instability, which are present in cases of brainstem premotor disturbances.

  14. Study on change of multi-modally evoked potentials in nasopharyngeal carcinoma patients after radiotherapy

    International Nuclear Information System (INIS)

    Qin Ling; Chen Jiaxin; Zhang Lixiang; Wang Tiejian; Han Min; Lu Xiaoling

    2001-01-01

    Objective: To investigate possible changes of multi-modally evoked potentials in nasopharyngeal carcinoma patients after radiotherapy. Methods: Altogether 48 nasopharyngeal carcinoma patients receiving primary conventional external beam irradiation were examined before and after radiotherapy to determine their brainstem auditory-evoked potential (BAEP), short-latency somatosensory-evoked potential (SLSEP) and pattern reversal visual-evoked potential (PRVEP). Results: In comparison with the conditions before radiotherapy, in different periods after radiotherapy abnormal peak latency and interval latency difference were found in BAEP, SLSEP and PRVEP. Conclusion: Nasopharyngeal carcinoma after radiotherapy may cause abnormal function of nerve conduction in early periods, which can be showed by BAEP, SLSEP, PRVEP, and injury can be timely detected if the three evoked potentials are used together. Thus authors suggest BAEP, SLSEP, PRVEP should be examined in nasopharyngeal carcinoma patients during and after the radiotherapy so as to find early damage in auditory somatosensory and visual conduction pathways

  15. Discovery of the first selective inhibitor of excitatory amino acid transporter subtype 1

    DEFF Research Database (Denmark)

    Jensen, Anders Asbjørn; Erichsen, Mette Navy; Nielsen, Christina Wøhlk

    2009-01-01

    The discovery of the first class of subtype-selective inhibitors of the human excitatory amino acid transporter subtype 1 (EAAT1) and its rat orthologue GLAST is reported. An opening structure-activity relationship of 25 analogues is presented that addresses the influence of substitutions at the 4......- and 7-positions of the parental skeleton 2-amino-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile. The most potent analogue 1o displays high nanomolar inhibitory activity at EAAT1 and a >400-fold selectivity over EAAT2 and EAAT3, making it a highly valuable pharmacological tool....

  16. Index finger somatosensory evoked potentials in blind Braille readers.

    Science.gov (United States)

    Giriyappa, Dayananda; Subrahmanyam, Roopakala Mysore; Rangashetty, Srinivasa; Sharma, Rajeev

    2009-01-01

    Traditionally, vision has been considered the dominant modality in our multi-sensory perception of the surrounding world. Sensory input via non-visual tracts becomes of greater behavioural relevance in totally blind individuals to enable effective interaction with the world around them. These include audition and tactile perceptions, leading to an augmentation in these perceptions when compared with normal sighted individuals. The objective of the present work was to study the index finger somatosensory evoked potentials (SEPs) in totally blind and normal sighted individuals. SEPs were recorded in 15 Braille reading totally blind females and compared with 15 age-matched normal sighted females. Latency and amplitudes of somatosensory evoked potential waveforms (N9, N13, and N20) were measured. Amplitude of N20 SEP (a cortical somatosensory evoked potential) was significantly larger in the totally blind than in normal sighted individuals (p Braille reading right index finger. Totally blind Braille readers have larger N20 amplitude, suggestive of greater somatosensory cortical representation of the Braille reading index finger.

  17. Altered Modulation of Silent Period in Tongue Motor Cortex of Persistent Developmental Stuttering in Relation to Stuttering Severity.

    Science.gov (United States)

    Busan, Pierpaolo; Del Ben, Giovanni; Bernardini, Simona; Natarelli, Giulia; Bencich, Marco; Monti, Fabrizio; Manganotti, Paolo; Battaglini, Piero Paolo

    2016-01-01

    Motor balance in developmental stuttering (DS) was investigated with Transcranial Magnetic Stimulation (TMS), with the aim to define novel neural markers of persistent DS in adulthood. Eleven DS adult males were evaluated with TMS on tongue primary motor cortex, compared to 15 matched fluent speakers, in a "state" condition (i.e. stutterers vs. fluent speakers, no overt stuttering). Motor and silent period thresholds (SPT), recruitment curves, and silent period durations were acquired by recording tongue motor evoked potentials. Tongue silent period duration was increased in DS, especially in the left hemisphere (Pstuttering severity. Pre-TMS electromyography data gave overlapping evidence. Findings suggest the existence of a complex intracortical balance in DS tongue primary motor cortex, with a particular interplay between excitatory and inhibitory mechanisms, also in neural substrates related to silent periods. Findings are discussed with respect to functional and structural impairments in stuttering, and are also proposed as novel neural markers of a stuttering "state" in persistent DS, helping to define more focused treatments (e.g. neuro-modulation).

  18. Newborn hearing screening with transient evoked otoacoustic emissions and automatic auditory brainstem response

    Directory of Open Access Journals (Sweden)

    Renata Mota Mamede de Carvallo

    2008-09-01

    Full Text Available Objective: The aim of the present investigation was to check Transient Evoked Otoacoustic Emissions and Automatic Auditory Brainstem Response tests applied together in regular nurseries and Newborn Intensive Care Units (NICU, as well as to describe and compare the results obtained in both groups. Methods: We tested 150 newborns from regular nurseries and 70 from NICU. Rresults: The newborn hearing screening results using Transient Evoked Otoacoustic Emissions and Automatic Auditory Brainstem Response tests could be applied to all babies. The “pass” result for the group of babies from the nursery was 94.7% using Transient Evoked Otoacoustic Emissions and 96% using Automatic Auditory Brainstem Response. The newborn intensive care unit group obtained 87.1% on Transient Evoked Otoacoustic Emissions and 80% on the Automatic Auditory Brainstem Response, and there was no statistical difference between the procedures when the groups were evaluated individually. However, comparing the groups, Transient Evoked Otoacoustic Emissions were presented in 94.7% of the nursery babies and in 87.1% in the group from the newborn intensive care unit. Considering the Automatic Auditory Brainstem Response, we found 96 and 87%, respectively. Cconclusions: Transient Evoked Otoacoustic Emissions and Automatic Auditory Brainstem Response had similar “pass” and “fail” results when the procedures were applied to neonates from the regular nursery, and the combined tests were more precise to detect hearing impairment in the newborn intensive care unit babies.

  19. Sex differences in the jealousy-evoking nature of a rival's body build

    NARCIS (Netherlands)

    Dijkstra, Pieternel; Buunk, Abraham (Bram)

    This study among 185 college students showed that potential rivals with a relatively low waist-to-hip ratio (WHR) evoked more jealousy in women than in men. In contrast, rivals with a relatively high shoulder-to-hip ratio (SHR) evoked more jealousy in men than in women, particularly when the rival

  20. Enhanced brainstem and cortical evoked response amplitudes: single-trial covariance analysis.

    Science.gov (United States)

    Galbraith, G C

    2001-06-01

    The purpose of the present study was to develop analytic procedures that improve the definition of sensory evoked response components. Such procedures could benefit all recordings but would especially benefit difficult recordings where many trials are contaminated by muscle and movement artifacts. First, cross-correlation and latency adjustment analyses were applied to the human brainstem frequency-following response and cortical auditory evoked response recorded on the same trials. Lagged cross-correlation functions were computed, for each of 17 subjects, between single-trial data and templates consisting of the sinusoid stimulus waveform for the brainstem response and the subject's own smoothed averaged evoked response P2 component for the cortical response. Trials were considered in the analysis only if the maximum correlation-squared (r2) exceeded .5 (negatively correlated trials were thus included). Identical correlation coefficients may be based on signals with quite different amplitudes, but it is possible to assess amplitude by the nonnormalized covariance function. Next, an algorithm is applied in which each trial with negative covariance is matched to a trial with similar, but positive, covariance and these matched-trial pairs are deleted. When an evoked response signal is present in the data, the majority of trials positively correlate with the template. Thus, a residual of positively correlated trials remains after matched covariance trials are deleted. When these residual trials are averaged, the resulting brainstem and cortical responses show greatly enhanced amplitudes. This result supports the utility of this analysis technique in clarifying and assessing evoked response signals.

  1. Developmental changes in electrophysiological properties and a transition from electrical to chemical coupling between excitatory layer 4 neurons in the rat barrel cortex

    Directory of Open Access Journals (Sweden)

    Fliza eValiullina

    2016-01-01

    Full Text Available During development, sensory systems switch from an immature to an adult mode of function along with the emergence of the active cortical states. Here, we used patch-clamp recordings from neocortical slices in vitro to characterize the developmental changes in the basic electrophysiological properties of excitatory L4 neurons and their connectivity before and after the developmental switch, which occurs in the rat barrel cortex in vivo at postnatal day P8. Prior to the switch, L4 neurons had lower resting membrane potentials, higher input resistance, lower membrane capacity, as well as action potentials (APs with smaller amplitudes, longer durations and higher AP thresholds compared to the neurons after the switch. A sustained firing pattern also emerged around the switch. Dual patch-clamp recordings from L4 neurons revealed that recurrent connections between L4 excitatory cells do not exist before and develop rapidly across the switch. In contrast, electrical coupling between these neurons waned around the switch. We suggest that maturation of electrophysiological features, particularly acquisition of a sustained firing pattern, and a transition from the immature electrical to mature chemical synaptic coupling between excitatory L4 neurons, contributes to the developmental switch in the cortical mode of function.

  2. Is Urgent Evoke a Digital Ba?

    DEFF Research Database (Denmark)

    Wichmand, Mette

    2018-01-01

    of such a platform, the World Bank’s online game Urgent Evoke, which has been designed with the pur- pose of engaging citizens in developing innovative solutions for sociopolitical problems like poverty. The analysis is based on Nonaka’s concept of Ba, which means “place” and is described as a platform for advancing...

  3. The excitatory/inhibitory input to orexin/hypocretin neuron soma undergoes day/night reorganization.

    Science.gov (United States)

    Laperchia, Claudia; Imperatore, Roberta; Azeez, Idris A; Del Gallo, Federico; Bertini, Giuseppe; Grassi-Zucconi, Gigliola; Cristino, Luigia; Bentivoglio, Marina

    2017-11-01

    Orexin (OX)/hypocretin-containing neurons are main regulators of wakefulness stability, arousal, and energy homeostasis. Their activity varies in relation to the animal's behavioral state. We here tested whether such variation is subserved by synaptic plasticity phenomena in basal conditions. Mice were sacrificed during day or night, at times when sleep or wake, respectively, predominates, as assessed by electroencephalography in matched mice. Triple immunofluorescence was used to visualize OX-A perikarya and varicosities containing the vesicular glutamate transporter (VGluT)2 or the vesicular GABA transporter (VGAT) combined with synaptophysin (Syn) as a presynaptic marker. Appositions on OX-A + somata were quantitatively analyzed in pairs of sections in epifluorescence and confocal microscopy. The combined total number of glutamatergic (Syn + /VGluT2 + ) and GABAergic (Syn + /VGAT + ) varicosities apposed to OX-A somata was similar during day and night. However, glutamatergic varicosities were significantly more numerous at night, whereas GABAergic varicosities prevailed in the day. Triple immunofluorescence in confocal microscopy was employed to visualize synapse scaffold proteins as postsynaptic markers and confirmed the nighttime prevalence of VGluT2 + together with postsynaptic density protein 95 + excitatory contacts, and daytime prevalence of VGAT + together with gephyrin + inhibitory contacts, while also showing that they formed synapses on OX-A + cell bodies. The findings reveal a daily reorganization of axosomatic synapses in orexinergic neurons, with a switch from a prevalence of excitatory innervation at a time corresponding to wakefulness to a prevalence of inhibitory innervations in the antiphase, at a time corresponding to sleep. This reorganization could represent a key mechanism of plasticity of the orexinergic network in basal conditions.

  4. Differences in context sensitivity for second-learned inhibitory and excitatory stimuli in AAB and ABC designs

    OpenAIRE

    Elgueta, Tito

    2014-01-01

    Bouton (1997) proposed a model to explain Pavlovian conditioning according to which the order of the associations (first-learned or second-learned), not the valence of the associations (inhibitory or excitatory), determines context sensitivity in AAB and ABC renewal designs. As a consequence, Bouton’s model does not predict important differences in context sensitivity between AAB and ABC designs. However, evidence suggests that there are indeed differences in context sensitivity between these...

  5. Evoked Emotions Predict Food Choice

    OpenAIRE

    Dalenberg, Jelle R.; Gutjar, Swetlana; ter Horst, Gert J.; de Graaf, Kees; Renken, Remco J.; Jager, Gerry

    2014-01-01

    In the current study we show that non-verbal food-evoked emotion scores significantly improve food choice prediction over merely liking scores. Previous research has shown that liking measures correlate with choice. However, liking is no strong predictor for food choice in real life environments. Therefore, the focus within recent studies shifted towards using emotion-profiling methods that successfully can discriminate between products that are equally liked. However, it is unclear how well ...

  6. Opiate-like excitatory effects of steroid sulfates and calcium-complexing agents given cerebroventricularly.

    Science.gov (United States)

    LaBella, F S; Havlicek, V; Pinsky, C

    1979-01-12

    Intracerebroventricular administration of 10--20 microgram of steroid-O-sulfates induced hypermotility, agitation, salivation, EEG abnormalities, stereotypies, wet dog shakes and seizures. Equivalent effects resulted from 30--200 microgram morphine sulfate (H2SO4 salt), 50 microgram EGTA or 300--400 microgram of sodium sulfate or phosphate, but not chloride, nitrate or acetate. Non-steroid sulfates, steroid glucuronides and steroid phosphates were inactive. Naloxone, previously found to antagonize the excitatory effects of androsterone sulfate, failed to antagonize those of cortisol sulfate, sodium sulfate or EGTA. These findings suggest a role for extracellular calcium ions and for sulfate derived from circulating steroids in central responses to opiates.

  7. Phencyclidine administration during neurodevelopment alters network activity in prefrontal cortex and hippocampus in adult rats.

    Science.gov (United States)

    Kjaerby, Celia; Hovelsø, Nanna; Dalby, Nils Ole; Sotty, Florence

    2017-08-01

    Symptoms of schizophrenia have been linked to insults during neurodevelopment such as NMDA receptor (NMDAR) antagonist exposure. In animal models, this leads to schizophrenia-like behavioral symptoms as well as molecular and functional changes within hippocampal and prefrontal regions. The aim of this study was to determine how administration of the NMDAR antagonist phencyclidine (PCP) during neurodevelopment affects functional network activity within the hippocampus and medial prefrontal cortex (mPFC). We recorded field potentials in vivo after electrical brain stem stimulation and observed a suppression of evoked theta power in ventral hippocampus, while evoked gamma power in mPFC was enhanced in rats administered with PCP neonatally. In addition, increased gamma synchrony elicited by acute administration of the NMDAR antagonist MK-801 was exaggerated in neonatal PCP animals. These data suggest that NMDAR antagonist exposure during brain development alters functional networks within hippocampus and mPFC possibly contributing to the reported behavioral symptoms of this animal model of schizophrenia. NEW & NOTEWORTHY We show that insults with a NMDA receptor antagonist during neurodevelopment lead to suppressed evoked theta oscillations in ventral hippocampus in adult rats, while evoked gamma oscillations are enhanced and hypersensitive to an acute challenge with a NMDA receptor antagonist in prefrontal cortex. These observations reveal the significance of neurodevelopmental disturbances in the evolvement of schizophrenia-like symptoms and contribute to the understanding of the functional deficits underlying aberrant behavior in this disease. Copyright © 2017 the American Physiological Society.

  8. Effect of peripherally and cortically evoked swallows on jaw reflex responses in anesthetized rabbits.

    Science.gov (United States)

    Suzuki, Taku; Yoshihara, Midori; Sakai, Shogo; Tsuji, Kojun; Nagoya, Kouta; Magara, Jin; Tsujimura, Takanori; Inoue, Makoto

    2018-05-03

    This study aimed to investigate whether the jaw-opening (JOR) and jaw-closing reflexes (JCR) are modulated during not only peripherally, but also centrally, evoked swallowing. Experiments were carried out on 24 adult male Japanese white rabbits. JORs were evoked by trigeminal stimulation at 1 Hz for 30 sec. In the middle 10 sec, either the superior laryngeal nerve (SLN) or cortical swallowing area (Cx) was simultaneously stimulated to evoke swallowing. The peak-to-peak JOR amplitude was reduced during the middle and late 10-sec periods (i.e., during and after SLN or Cx stimulation), and the reduction was dependent on the current intensity of SLN/Cx stimulation: greater SLN/Cx stimulus current resulted in greater JOR inhibition. The reduction rate was significantly greater during Cx stimulation than during SLN stimulation. The amplitude returned to baseline 2 min after 10-sec SLN/Cx stimulation. The effect of co-stimulation of SLN and Cx was significantly greater than that of SLN stimulation alone. There were no significant differences in any parameters of the JCR between conditions. These results clearly showed that JOR responses were significantly suppressed, not only during peripherally evoked swallowing but also during centrally evoked swallowing, and that the inhibitory effect is likely to be larger during centrally compared with peripherally evoked swallowing. The functional implications of these results are discussed. Copyright © 2018. Published by Elsevier B.V.

  9. The Relationship of Visual Evoked Potential Asymmetries to the Performance of Sonar Operators

    Science.gov (United States)

    1981-08-11

    also been related to EP variability. Schizophrenic adults and patients with Korsakoff’s Syndrome have shown higher evoked potential variability than...average evoked response in Korsakoff patients. J. Psychiatry Res. 6: 253-260, 1969. Santoro, T. and D. Fender. Rules for the perception of

  10. Low level postnatal methylmercury exposure in vivo alters developmental forms of short-term synaptic plasticity in the visual cortex of rat

    International Nuclear Information System (INIS)

    Dasari, Sameera; Yuan, Yukun

    2009-01-01

    Methylmercury (MeHg) has been previously shown to affect neurotransmitter release. Short-term synaptic plasticity (STP) is primarily related to changes in the probability of neurotransmitter release. To determine if MeHg affects STP development, we examined STP forms in the visual cortex of rat following in vivo MeHg exposure. Neonatal rats received 0 (0.9% NaCl), 0.75 or 1.5 mg/kg/day MeHg subcutaneously for 15 or 30 days beginning on postnatal day 5, after which visual cortical slices were prepared for field potential recordings. In slices prepared from rats treated with vehicle, field excitatory postsynaptic potentials (fEPSPs) evoked by paired-pulse stimulation at 20-200 ms inter-stimulus intervals showed a depression (PPD) of the second fEPSP (fEPSP2). PPD was also seen in slices prepared from rats after 15 day treatment with 0.75 or 1.5 mg/kg/day MeHg. However, longer duration treatment (30 days) with either dose of MeHg resulted in paired-pulse facilitation (PPF) of fEPSP2 in the majority of slices examined. PPF remained observable in slices prepared from animals in which MeHg exposure had been terminated for 30 days after completion of the initial 30 day MeHg treatment, whereas slices from control animals still showed PPD. MeHg did not cause any frequency- or region-preferential effect on STP. Manipulations of [Ca 2+ ] e or application of the GABA A receptor antagonist bicuculline could alter the strength and polarity of MeHg-induced changes in STP. Thus, these data suggest that low level postnatal MeHg exposure interferes with the developmental transformation of STP in the visual cortex, which is a long-lasting effect.

  11. A new highly selective metabotropic excitatory amino acid agonist: 2-amino-4-(3-hydroxy-5-methylisoxazol-4-yl)butyric acid

    DEFF Research Database (Denmark)

    Bräuner-Osborne, Hans; Sløk, F A; Skjaerbaek, N

    1996-01-01

    The homologous series of acidic amino acids, ranging from aspartic acid (1) to 2-aminosuberic acid (5), and the corresponding series of 3-isoxazolol bioisosteres of these amino acids, ranging from (RS)-2-amino-2-(3-hydroxy-5-methylisoxazol-4-yl)acetic acid (AMAA, 6) to (RS)-2-amino-6-(3-hydroxy-5......-methylisoxazol-4-yl)hexanoic acid (10), were tested as ligands for metabotropic excitatory amino acid receptors (mGlu1 alpha, mGlu2, mGlu4a, and mGlu6). Whereas AMAA (6) and (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propinoic acid (AMPA, 7) are potent and highly selective agonists at N......-methyl-D-aspartic acid (NMDA) and AMPA receptors, respectively, the higher homologue of AMPA (7), (RS)-2-amino-4-(3-hydroxy-5-methylisoxazol-4-yl)butyric acid (homo-AMPA, 8), is inactive at ionotropic excitatory amino acid receptors. Homo-AMPA (8), which is a 3-isoxazolol bioisostere of 2-aminoadipic acid (3), was...

  12. Conduction velocity of the human spinothalamic tract as assessed by laser evoked potentials

    DEFF Research Database (Denmark)

    Cruccu, G.; Iannetti, G. D.; Agostino, R.

    2000-01-01

    To study the conduction velocity of the spinothalamic tract (STT) we delivered CO2 laser pulses, evoking pinprick sensations, to the skin overlying the vertebral spinous processes at different spinal levels from C5 to T10 and recorded evoked potentials (LEPs) in 15 healthy human subjects...

  13. Evidence that 5-hydroxytryptamine3 receptors mediate cytotoxic drug and radiation-evoked emesis

    International Nuclear Information System (INIS)

    Miner, W.D.; Sanger, G.J.; Turner, D.H.

    1987-01-01

    The involvement of 5-hydroxytryptamine (5-HT) 5-HT 3 receptors in the mechanisms of severe emesis evoked by cytotoxic drugs or by total body irradiation have been studied in ferrets. Anti-emetic compounds tested were domperidone (a dopamine antagonist), metoclopramide (a gastric motility stimulant and dopamine antagonist at conventional doses, a 5-HT 3 receptor antagonist at higher doses) and BRL 24924 (a potent gastric motility stimulant and a 5-HT 3 receptor antagonist). Domperidone or metoclopramide prevented apomorphine-evoked emesis, whereas BRL 24924 did not. Similar doses of domperidone did not prevent emesis evoked by cis-platin or by total body irradiation, whereas metoclopramide or BRL 24924 greatly reduced or prevented these types of emesis. Metoclopramide and BRL 24924 also prevented emesis evoked by a combination of doxorubicin and cyclophosphamide. These results are discussed in terms of a fundamental role for 5-HT 3 receptors in the mechanisms mediating severely emetogenic cancer treatment therapies. (author)

  14. Interhemispheric Asymmetries in Visual Evoked Potential Amplitude

    Science.gov (United States)

    1980-06-12

    Layne, 1965) and of patients with Korsakoff’s syndrome (Malerstein and Callaway, 1969) . In the schizophrenics, the high variability is related to poor...communication. Malerstein, A. J., Callaway, E. Two-tone average evoked response in Korsakoff patients. J. Psychiatr. Res. 6: 253-260, 1969. Marsh, G

  15. Visual cortical somatosensory and brainstem auditory evoked potentials following incidental irradiation of the rhombencephalon

    Energy Technology Data Exchange (ETDEWEB)

    Nightingale, S. (Royal Victoria Infirmary, Newcastle upon Tyne (UK)); Schofield, I.S.; Dawes, P.J.D.K. (Newcastle upon Tyne Univ. (UK). Newcastle General Hospital)

    1984-01-01

    Visual, cortical somatosensory and brainstem auditory evoked potentials were recorded before incidental irradiation of the rhombencephalon during radiotherapy in and around the middle ear, and at 11 weeks and eight months after completion of treatment. No patient experienced neurological symptoms during this period. No consistent changes in evoked potentials were found. The failure to demonstrate subclinical radiation-induced demyelination suggests either that the syndrome of early-delayed radiation rhombencephalopathy occurs in an idiosyncratic manner, or that any subclinical lesions are not detectable by serial evoked potential recordings.

  16. Beta-Sulfonamido Functionalized Aspartate Analogs as Excitatory Amino Acid Transporter Inhibitors: Distinct Subtype-Selectivity Profiles Arising from Subtle Structural Differences

    DEFF Research Database (Denmark)

    Hansen, Jacob Christian; Bjørn-Yoshimoto, Walden Emil; Bisballe, Niels

    2016-01-01

    In this study inspired by previous work on 3-substituted Asp analogues, we designed and synthesized a total of 32 β-sulfonamide Asp analogues and characterized their pharmacological properties at the excitatory amino acid transporter subtypes EAAT1, EAAT2, and EAAT3. In addition to several potent...

  17. Contextual Learning Requires Functional Diversity at Excitatory and Inhibitory Synapses onto CA1 Pyramidal Neurons

    Directory of Open Access Journals (Sweden)

    Dai Mitsushima

    2015-01-01

    Full Text Available Although the hippocampus is processing temporal and spatial information in particular context, the encoding rule creating memory is completely unknown. To examine the mechanism, we trained rats on an inhibitory avoidance (IA task, a hippocampus-dependent rapid one-trial contextual learning paradigm. By combining Herpes virus-mediated in vivo gene delivery with in vitro patch-clamp recordings, I reported contextual learning drives GluR1-containing AMPA receptors into CA3-CA1 synapses. The molecular event is required for contextual memory, since bilateral expression of delivery blocker in CA1 successfully blocked IA learning. Moreover, I found a logarithmic correlation between the number of delivery blocking cells and learning performance. Considering that one all-or-none device can process 1-bit of data per clock (Nobert Wiener 1961, the logarithmic correlation may provides evidence that CA1 neurons transmit essential data of contextual information. Further, I recently reported critical role of acetylcholine as an intrinsic trigger of learning-dependent synaptic plasticity. IA training induced ACh release in CA1 that strengthened not only AMPA receptor-mediated excitatory synapses, but also GABAA receptor-mediated inhibitory synapses on each CA1 neuron. More importantly, IA-trained rats showed individually different excitatory and inhibitory synaptic inputs with wide variation on each CA1 neuron. Here I propose a new hypothesis that the diversity of synaptic inputs on CA1 neurons may depict cell-specific outputs processing experienced episodes after training.

  18. Repeated Neck Restraint Stress Bidirectionally Modulates Excitatory Transmission in the Dentate Gyrus and Performance in a Hippocampus-dependent Memory Task.

    Science.gov (United States)

    Spyrka, Jadwiga; Hess, Grzegorz

    2018-05-21

    The consequences of stress depend on characteristics of the stressor, including the duration of exposure, severity, and predictability. Exposure of mice to repeated neck restraint has been shown to bidirectionally modulate the potential for long-term potentiation (LTP) in the dentate gyrus (DG) in a manner dependent on the number of restraint repetitions, but the influence of repeated brief neck restraint on electrophysiology of single DG neurons has not yet been investigated. Here, we aimed at finding the effects of 1, 3, 7, 14, or 21 daily neck restraint sessions lasting 10 min on electrophysiological characteristics of DG granule cells as well as excitatory and inhibitory synaptic inputs to these neurons. While the excitability of DG granule cells and inhibitory synaptic transmission were unchanged, neck restraint decreased the frequency of spontaneous excitatory currents after three repetitions but enhanced it after 14 and 21 repetitions. The consequences of repeated neck restraint on hippocampus-dependent memory were investigated using the object location test (OLT). Neck restraint stress impaired cognitive performance in the OLT after three repetitions but improved it after 14 and 21 repetitions. Mice subjected to three neck restraint sessions displayed an increase in the measures of depressive and anxiety-like behaviors, however, prolongation of the exposure to neck restraint resulted in a gradual decline in the intensity of these measures. These data indicate that stress imposed by an increasing number of repeated neck restraint episodes bidirectionally modulates both excitatory synaptic transmission in the DG and cognitive performance in the object location memory task. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  19. Music-evoked emotions in schizophrenia.

    Science.gov (United States)

    Abe, Daijyu; Arai, Makoto; Itokawa, Masanari

    2017-07-01

    Previous studies have reported that people with schizophrenia have impaired musical abilities. Here we developed a simple music-based assay to assess patient's ability to associate a minor chord with sadness. We further characterize correlations between impaired musical responses and psychiatric symptoms. We exposed participants sequentially to two sets of sound stimuli, first a C-major progression and chord, and second a C-minor progression and chord. Participants were asked which stimulus they associated with sadness, the first set, the second set, or neither. The severity of psychiatric symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS). Study participants were 29 patients diagnosed with schizophrenia and 29 healthy volunteers matched in age, gender and musical background. 37.9% (95% confidence interval [CI]:19.1-56.7) of patients with schizophrenia associated the minor chord set as sad, compared with 97.9% (95%CI: 89.5-103.6) of controls. Four patients were diagnosed with treatment-resistant schizophrenia, and all four failed to associate the minor chord with sadness. Patients who did not recognize minor chords as sad had significantly higher scores on all PANSS subscales. A simple test allows music-evoked emotions to be assessed in schizophrenia patient, and may show potential relationships between music-evoked emotions and psychiatric symptoms. Copyright © 2016. Published by Elsevier B.V.

  20. Right hemispheric dominance of visual phenomena evoked by intracerebral stimulation of the human visual cortex.

    Science.gov (United States)

    Jonas, Jacques; Frismand, Solène; Vignal, Jean-Pierre; Colnat-Coulbois, Sophie; Koessler, Laurent; Vespignani, Hervé; Rossion, Bruno; Maillard, Louis

    2014-07-01

    Electrical brain stimulation can provide important information about the functional organization of the human visual cortex. Here, we report the visual phenomena evoked by a large number (562) of intracerebral electrical stimulations performed at low-intensity with depth electrodes implanted in the occipito-parieto-temporal cortex of 22 epileptic patients. Focal electrical stimulation evoked primarily visual hallucinations with various complexities: simple (spot or blob), intermediary (geometric forms), or complex meaningful shapes (faces); visual illusions and impairments of visual recognition were more rarely observed. With the exception of the most posterior cortical sites, the probability of evoking a visual phenomenon was significantly higher in the right than the left hemisphere. Intermediary and complex hallucinations, illusions, and visual recognition impairments were almost exclusively evoked by stimulation in the right hemisphere. The probability of evoking a visual phenomenon decreased substantially from the occipital pole to the most anterior sites of the temporal lobe, and this decrease was more pronounced in the left hemisphere. The greater sensitivity of the right occipito-parieto-temporal regions to intracerebral electrical stimulation to evoke visual phenomena supports a predominant role of right hemispheric visual areas from perception to recognition of visual forms, regardless of visuospatial and attentional factors. Copyright © 2013 Wiley Periodicals, Inc.

  1. Altered Balance of Receptive Field Excitation and Suppression in Visual Cortex of Amblyopic Macaque Monkeys.

    Science.gov (United States)

    Hallum, Luke E; Shooner, Christopher; Kumbhani, Romesh D; Kelly, Jenna G; García-Marín, Virginia; Majaj, Najib J; Movshon, J Anthony; Kiorpes, Lynne

    2017-08-23

    In amblyopia, a visual disorder caused by abnormal visual experience during development, the amblyopic eye (AE) loses visual sensitivity whereas the fellow eye (FE) is largely unaffected. Binocular vision in amblyopes is often disrupted by interocular suppression. We used 96-electrode arrays to record neurons and neuronal groups in areas V1 and V2 of six female macaque monkeys ( Macaca nemestrina ) made amblyopic by artificial strabismus or anisometropia in early life, as well as two visually normal female controls. To measure suppressive binocular interactions directly, we recorded neuronal responses to dichoptic stimulation. We stimulated both eyes simultaneously with large sinusoidal gratings, controlling their contrast independently with raised-cosine modulators of different orientations and spatial frequencies. We modeled each eye's receptive field at each cortical site using a difference of Gaussian envelopes and derived estimates of the strength of central excitation and surround suppression. We used these estimates to calculate ocular dominance separately for excitation and suppression. Excitatory drive from the FE dominated amblyopic visual cortex, especially in more severe amblyopes, but suppression from both the FE and AEs was prevalent in all animals. This imbalance created strong interocular suppression in deep amblyopes: increasing contrast in the AE decreased responses at binocular cortical sites. These response patterns reveal mechanisms that likely contribute to the interocular suppression that disrupts vision in amblyopes. SIGNIFICANCE STATEMENT Amblyopia is a developmental visual disorder that alters both monocular vision and binocular interaction. Using microelectrode arrays, we examined binocular interaction in primary visual cortex and V2 of six amblyopic macaque monkeys ( Macaca nemestrina ) and two visually normal controls. By stimulating the eyes dichoptically, we showed that, in amblyopic cortex, the binocular combination of signals is

  2. Identification of Chloride Channels CLCN3 and CLCN5 Mediating the Excitatory Cl− Currents Activated by Sphingosine-1-Phosphate in Sensory Neurons

    Science.gov (United States)

    Qi, Yanmei; Mair, Norbert; Kummer, Kai K.; Leitner, Michael G.; Camprubí-Robles, María; Langeslag, Michiel; Kress, Michaela

    2018-01-01

    Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid involved in numerous physiological and pathophysiological processes. We have previously reported a S1P-induced nocifensive response in mice by excitation of sensory neurons via activation of an excitatory chloride current. The underlying molecular mechanism for the S1P-induced chloride conductance remains elusive. In the present study, we identified two CLCN voltage-gated chloride channels, CLCN3 and CLCN5, which mediated a S1P-induced excitatory Cl− current in sensory neurons by combining RNA-seq, adenovirus-based gene silencing and whole-cell electrophysiological voltage-clamp recordings. Downregulation of CLCN3 and CLCN5 channels by adenovirus-mediated delivery of shRNA dramatically reduced S1P-induced Cl− current and membrane depolarization in sensory neurons. The mechanism of S1P-induced activation of the chloride current involved Rho GTPase but not Rho-associated protein kinase. Although S1P-induced potentiation of TRPV1-mediated ionic currents also involved Rho-dependent process, the lack of correlation of the S1P-activated Cl− current and the potentiation of TRPV1 by S1P suggests that CLCN3 and CLCN5 are necessary components for S1P-induced excitatory Cl− currents but not for the amplification of TRPV1-mediated currents in sensory neurons. This study provides a novel mechanistic insight into the importance of bioactive sphingolipids in nociception. PMID:29479306

  3. Identification of Chloride Channels CLCN3 and CLCN5 Mediating the Excitatory Cl− Currents Activated by Sphingosine-1-Phosphate in Sensory Neurons

    Directory of Open Access Journals (Sweden)

    Yanmei Qi

    2018-02-01

    Full Text Available Sphingosine-1-phosphate (S1P is a bioactive sphingolipid involved in numerous physiological and pathophysiological processes. We have previously reported a S1P-induced nocifensive response in mice by excitation of sensory neurons via activation of an excitatory chloride current. The underlying molecular mechanism for the S1P-induced chloride conductance remains elusive. In the present study, we identified two CLCN voltage-gated chloride channels, CLCN3 and CLCN5, which mediated a S1P-induced excitatory Cl− current in sensory neurons by combining RNA-seq, adenovirus-based gene silencing and whole-cell electrophysiological voltage-clamp recordings. Downregulation of CLCN3 and CLCN5 channels by adenovirus-mediated delivery of shRNA dramatically reduced S1P-induced Cl− current and membrane depolarization in sensory neurons. The mechanism of S1P-induced activation of the chloride current involved Rho GTPase but not Rho-associated protein kinase. Although S1P-induced potentiation of TRPV1-mediated ionic currents also involved Rho-dependent process, the lack of correlation of the S1P-activated Cl− current and the potentiation of TRPV1 by S1P suggests that CLCN3 and CLCN5 are necessary components for S1P-induced excitatory Cl− currents but not for the amplification of TRPV1-mediated currents in sensory neurons. This study provides a novel mechanistic insight into the importance of bioactive sphingolipids in nociception.

  4. Temporal processing and long-latency auditory evoked potential in stutterers.

    Science.gov (United States)

    Prestes, Raquel; de Andrade, Adriana Neves; Santos, Renata Beatriz Fernandes; Marangoni, Andrea Tortosa; Schiefer, Ana Maria; Gil, Daniela

    Stuttering is a speech fluency disorder, and may be associated with neuroaudiological factors linked to central auditory processing, including changes in auditory processing skills and temporal resolution. To characterize the temporal processing and long-latency auditory evoked potential in stutterers and to compare them with non-stutterers. The study included 41 right-handed subjects, aged 18-46 years, divided into two groups: stutterers (n=20) and non-stutters (n=21), compared according to age, education, and sex. All subjects were submitted to the duration pattern tests, random gap detection test, and long-latency auditory evoked potential. Individuals who stutter showed poorer performance on Duration Pattern and Random Gap Detection tests when compared with fluent individuals. In the long-latency auditory evoked potential, there was a difference in the latency of N2 and P3 components; stutterers had higher latency values. Stutterers have poor performance in temporal processing and higher latency values for N2 and P3 components. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  5. Temporal processing and long-latency auditory evoked potential in stutterers

    Directory of Open Access Journals (Sweden)

    Raquel Prestes

    Full Text Available Abstract Introduction: Stuttering is a speech fluency disorder, and may be associated with neuroaudiological factors linked to central auditory processing, including changes in auditory processing skills and temporal resolution. Objective: To characterize the temporal processing and long-latency auditory evoked potential in stutterers and to compare them with non-stutterers. Methods: The study included 41 right-handed subjects, aged 18-46 years, divided into two groups: stutterers (n = 20 and non-stutters (n = 21, compared according to age, education, and sex. All subjects were submitted to the duration pattern tests, random gap detection test, and long-latency auditory evoked potential. Results: Individuals who stutter showed poorer performance on Duration Pattern and Random Gap Detection tests when compared with fluent individuals. In the long-latency auditory evoked potential, there was a difference in the latency of N2 and P3 components; stutterers had higher latency values. Conclusion: Stutterers have poor performance in temporal processing and higher latency values for N2 and P3 components.

  6. Pattern visual evoked potentials in malingering.

    Science.gov (United States)

    Nakamura, A; Akio, T; Matsuda, E; Wakami, Y

    2001-03-01

    We previously developed a new method for estimating objective visual acuity by means of pattern visual evoked potentials (PVEP). In this study, this method was applied to the diagnosis of malingering. Six patients ranging in age from 40 to 54 years (mean 47 years) with suspected malingering were evaluated by means of the visual evoked potential test, optokinetic nystagmus (OKN) inhibition test, and the visual field test. In the PVEP study, the stimulus consisted of black and white checkerboards (39', 26', 15', and 9') with a visual angle of 8 degrees, contrast level of 15%, and a frequency of 0.7 Hz. One hundred PVEP responses were averaged per session. Routine ophthalmic examinations were normal in all patients. Five patients had a tubularly constricted visual field, and the remaining patient had a normal visual field. The objective visual acuities of the six patients estimated from PVEP were better than their subjective visual acuities estimated with Landolt rings. Among a variety of psychophysical and electrophysiologic ancillary tests, we consider our PVEP method a useful method for objectively determining visual acuity in a patient with signs of ocular malingering.

  7. Brainstem auditory evoked potentials in horses

    Directory of Open Access Journals (Sweden)

    Juliana Almeida Nogueira da Gama

    2016-04-01

    Full Text Available ABSTRACT: The brainstem auditory evoked potential (BAEP evaluates the integrity of the auditory pathways to the brainstem. The aim of this study was to evoke BAEPs in 21 clinically normal horses. The animals were sedated with detomidine hydrochloride (0.013mg.kg-1 BW. Earphones were inserted and rarefaction clicks at 90 dB and noise masking at 40 dB were used. After performing the test, the latencies of waves (I, II, III, IV, and V and interpeaks(I-III, III-V, and I-V were identified. The mean latencies of the waves were as follows: wave I, 2.4 ms; wave II, 2.24 ms; wave III, 3.61ms; wave IV, 4.61ms; and wave V, 5.49ms. The mean latencies of the interpeaks were as follows: I-III, 1.37ms; III-V, 1.88ms; and I-V, 3.26ms. This is the first study using BAEPs in horses in Brazil, and the observed latencies will be used as normative data for the interpretation of tests performed on horses with changes related to auditory system or neurologic abnormalities.

  8. Clinical and evoked pain, personality traits, and emotional states: can familial confounding explain the associations?

    Science.gov (United States)

    Strachan, Eric; Poeschla, Brian; Dansie, Elizabeth; Succop, Annemarie; Chopko, Laura; Afari, Niloofar

    2015-01-01

    Pain is a complex phenomenon influenced by context and person-specific factors. Affective dimensions of pain involve both enduring personality traits and fleeting emotional states. We examined how personality traits and emotional states are linked with clinical and evoked pain in a twin sample. 99 female twin pairs were evaluated for clinical and evoked pain using the McGill Pain Questionnaire (MPQ) and dolorimetry, and completed the 120-item International Personality Item Pool (IPIP), the Positive and Negative Affect Scale (PANAS), and ratings of stress and mood. Using a co-twin control design we examined a) the relationship of personality traits and emotional states with clinical and evoked pain and b) whether genetics and common environment (i.e. familial factors) may account for the associations. Neuroticism was associated with the sensory component of the MPQ; this relationship was not confounded by familial factors. None of the emotional state measures was associated with the MPQ. PANAS negative affect was associated with lower evoked pressure pain threshold and tolerance; these associations were confounded by familial factors. There were no associations between IPIP traits and evoked pain. A relationship exists between neuroticism and clinical pain that is not confounded by familial factors. There is no similar relationship between negative emotional states and clinical pain. In contrast, the relationship between negative emotional states and evoked pain is strong while the relationship with enduring personality traits is weak. The relationship between negative emotional states and evoked pain appears to be non-causal and due to familial factors. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Visual cortical somatosensory and brainstem auditory evoked potentials following incidental irradiation of the rhombencephalon

    International Nuclear Information System (INIS)

    Nightingale, S.; Schofield, I.S.; Dawes, P.J.D.K.

    1984-01-01

    Visual, cortical somatosensory and brainstem auditory evoked potentials were recorded before incidental irradiation of the rhombencephalon during radiotherapy in and around the middle ear, and at 11 weeks and eight months after completion of treatment. No patient experienced neurological symptoms during this period. No consistent changes in evoked potentials were found. The failure to demonstrate subclinical radiation-induced demyelination suggests either that the syndrome of early-delayed radiation rhombencephalopathy occurs in an idiosyncratic manner, or that any subclinical lesions are not detectable by serial evoked potential recordings. (author)

  10. Proprioceptive evoked potentials in man

    DEFF Research Database (Denmark)

    Arnfred, S; Chen, A C; Eder, Derek N

    2000-01-01

    We studied cerebral evoked potentials on the scalp to the stimulation of the right hand from a change in weight of 400-480 g in ten subjects. Rise-time was 20g/10 ms, Inter Stimulus Interval 2s and stimulus duration was 100 ms. The cerebral activations were a double positive contralateral C3'/P70......). Further studies of the PEP are needed to assess the influence of load manipulations and of muscle contraction and to explore the effect of attentional manipulation....

  11. Differential effect of ketamine and lidocaine on spontaneous and mechanical evoked pain in patients with nerve injury pain

    DEFF Research Database (Denmark)

    Gottrup, Hanne; Bach, Flemming Winther; Juhl, Gitte Irene

    2006-01-01

    ketamine, an N-methyl-D-aspartate receptor antagonist and lidocaine, a sodium channel blocker, on spontaneous pain, brush-evoked pain, and pinprick-evoked pain in patients with nerve injury pain. METHODS: Twenty patients participated in two randomized, double-blinded, placebo-controlled, crossover...... experiments in which they, on four different days, received a 30-minute intravenous infusion of ketamine (0.24 mg/kg), lidocaine (5 mg/kg), or saline. Ongoing pain, pain evoked by brush and repetitive pinprick stimuli, and acetone was measured before, during, and after infusion. RESULTS: Ketamine...... significantly reduced ongoing pain and evoked pain to brush and pinprick, whereas lidocaine only reduced evoked pain to repetitive pinprick stimuli. In individual patients, there was no correlation between the pain-relieving effect of lidocaine and ketamine on ongoing or mechanically evoked pains. CONCLUSIONS...

  12. Dynamic encoding of natural luminance sequences by LGN bursts.

    Directory of Open Access Journals (Sweden)

    Nicholas A Lesica

    2006-07-01

    Full Text Available In the lateral geniculate nucleus (LGN of the thalamus, visual stimulation produces two distinct types of responses known as tonic and burst. Due to the dynamics of the T-type Ca(2+ channels involved in burst generation, the type of response evoked by a particular stimulus depends on the resting membrane potential, which is controlled by a network of modulatory connections from other brain areas. In this study, we use simulated responses to natural scene movies to describe how modulatory and stimulus-driven changes in LGN membrane potential interact to determine the luminance sequences that trigger burst responses. We find that at low resting potentials, when the T channels are de-inactivated and bursts are relatively frequent, an excitatory stimulus transient alone is sufficient to evoke a burst. However, to evoke a burst at high resting potentials, when the T channels are inactivated and bursts are relatively rare, prolonged inhibitory stimulation followed by an excitatory transient is required. We also observe evidence of these effects in vivo, where analysis of experimental recordings demonstrates that the luminance sequences that trigger bursts can vary dramatically with the overall burst percentage of the response. To characterize the functional consequences of the effects of resting potential on burst generation, we simulate LGN responses to different luminance sequences at a range of resting potentials with and without a mechanism for generating bursts. Using analysis based on signal detection theory, we show that bursts enhance detection of specific luminance sequences, ranging from the onset of excitatory sequences at low resting potentials to the offset of inhibitory sequences at high resting potentials. These results suggest a dynamic role for burst responses during visual processing that may change according to behavioral state.

  13. Auditory and visual evoked potentials during hyperoxia

    Science.gov (United States)

    Smith, D. B. D.; Strawbridge, P. J.

    1974-01-01

    Experimental study of the auditory and visual averaged evoked potentials (AEPs) recorded during hyperoxia, and investigation of the effect of hyperoxia on the so-called contingent negative variation (CNV). No effect of hyperoxia was found on the auditory AEP, the visual AEP, or the CNV. Comparisons with previous studies are discussed.

  14. Reversal of Cocaine-Associated Synaptic Plasticity in Medial Prefrontal Cortex Parallels Elimination of Memory Retrieval.

    Science.gov (United States)

    Otis, James M; Mueller, Devin

    2017-09-01

    Addiction is characterized by abnormalities in prefrontal cortex that are thought to allow drug-associated cues to drive compulsive drug seeking and taking. Identification and reversal of these pathologic neuroadaptations are therefore critical for treatment of addiction. Previous studies using rodents reveal that drugs of abuse cause dendritic spine plasticity in prelimbic medial prefrontal cortex (PL-mPFC) pyramidal neurons, a phenomenon that correlates with the strength of drug-associated memories in vivo. Thus, we hypothesized that cocaine-evoked plasticity in PL-mPFC may underlie cocaine-associated memory retrieval, and therefore disruption of this plasticity would prevent retrieval. Indeed, using patch clamp electrophysiology we find that cocaine place conditioning increases excitatory presynaptic and postsynaptic transmission in rat PL-mPFC pyramidal neurons. This was accounted for by increases in excitatory presynaptic release, paired-pulse facilitation, and increased AMPA receptor transmission. Noradrenergic signaling is known to maintain glutamatergic plasticity upon reactivation of modified circuits, and we therefore next determined whether inhibition of noradrenergic signaling during memory reactivation would reverse the cocaine-evoked plasticity and/or disrupt the cocaine-associated memory. We find that administration of the β-adrenergic receptor antagonist propranolol before memory retrieval, but not after (during memory reconsolidation), reverses the cocaine-evoked presynaptic and postsynaptic modifications in PL-mPFC and causes long-lasting memory impairments. Taken together, these data reveal that cocaine-evoked synaptic plasticity in PL-mPFC is reversible in vivo, and suggest a novel strategy that would allow normalization of prefrontal circuitry in addiction.

  15. Actin-Dependent Alterations of Dendritic Spine Morphology in Shankopathies

    Directory of Open Access Journals (Sweden)

    Tasnuva Sarowar

    2016-01-01

    Full Text Available Shank proteins (Shank1, Shank2, and Shank3 act as scaffolding molecules in the postsynaptic density of many excitatory neurons. Mutations in SHANK genes, in particular SHANK2 and SHANK3, lead to autism spectrum disorders (ASD in both human and mouse models. Shank3 proteins are made of several domains—the Shank/ProSAP N-terminal (SPN domain, ankyrin repeats, SH3 domain, PDZ domain, a proline-rich region, and the sterile alpha motif (SAM domain. Via various binding partners of these domains, Shank3 is able to bind and interact with a wide range of proteins including modulators of small GTPases such as RICH2, a RhoGAP protein, and βPIX, a RhoGEF protein for Rac1 and Cdc42, actin binding proteins and actin modulators. Dysregulation of all isoforms of Shank proteins, but especially Shank3, leads to alterations in spine morphogenesis, shape, and activity of the synapse via altering actin dynamics. Therefore, here, we highlight the role of Shank proteins as modulators of small GTPases and, ultimately, actin dynamics, as found in multiple in vitro and in vivo models. The failure to mediate this regulatory role might present a shared mechanism in the pathophysiology of autism-associated mutations, which leads to dysregulation of spine morphogenesis and synaptic signaling.

  16. Abnormal short-latency synaptic plasticity in the motor cortex of subjects with Becker muscular dystrophy: a rTMS study.

    Science.gov (United States)

    Golaszewski, Stefan; Schwenker, Kerstin; Bergmann, Jürgen; Brigo, Francesco; Christova, Monica; Trinka, Eugen; Nardone, Raffaele

    2016-01-01

    We used repetitive transcranial magnetic stimulation (rTMS) to further investigate motor cortex excitability in 13 patients with Becker muscular dystrophy (BMD), six of them with slight mental retardation. RTMS delivered at 5Hz frequency and suprathreshold intensity progressively increases the size of motor evoked potentials (MEPs) in healthy subjects; the rTMS-induced facilitation of MEPs was significantly reduced in the BMD patients mentally retarded or classified as borderline when compared with age-matched control subjects and the BMD patients with normal intelligence. The increase in the duration of the cortical silent period was similar in both patient groups and controls. These findings suggest an altered cortical short-term synaptic plasticity in glutamate-dependent excitatory circuits within the motor cortex in BMD patients with intellectual disabilities. RTMS studies may shed new light on the physiological mechanisms of cortical involvement in dystrophinopathies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Auditory brainstem activity and development evoked by apical versus basal cochlear implant electrode stimulation in children.

    Science.gov (United States)

    Gordon, K A; Papsin, B C; Harrison, R V

    2007-08-01

    The role of apical versus basal cochlear implant electrode stimulation on central auditory development was examined. We hypothesized that, in children with early onset deafness, auditory development evoked by basal electrode stimulation would differ from that evoked more apically. Responses of the auditory nerve and brainstem, evoked by an apical and a basal implant electrode, were measured over the first year of cochlear implant use in 50 children with early onset severe to profound deafness who used hearing aids prior to implantation. Responses at initial stimulation were of larger amplitude and shorter latency when evoked by the apical electrode. No significant effects of residual hearing or age were found on initial response amplitudes or latencies. With implant use, responses evoked by both electrodes showed decreases in wave and interwave latencies reflecting decreased neural conduction time through the brainstem. Apical versus basal differences persisted with implant experience with one exception; eIII-eV interlatency differences decreased with implant use. Acute stimulation shows prolongation of basally versus apically evoked auditory nerve and brainstem responses in children with severe to profound deafness. Interwave latencies reflecting neural conduction along the caudal and rostral portions of the brainstem decreased over the first year of implant use. Differences in neural conduction times evoked by apical versus basal electrode stimulation persisted in the caudal but not rostral brainstem. Activity-dependent changes of the auditory brainstem occur in response to both apical and basal cochlear implant electrode stimulation.

  18. Mapping cell-specific functional connections in the mouse brain using ChR2-evoked hemodynamics (Conference Presentation)

    Science.gov (United States)

    Bauer, Adam Q.; Kraft, Andrew; Baxter, Grant A.; Bruchas, Michael; Lee, Jin-Moo; Culver, Joseph P.

    2017-02-01

    Functional magnetic resonance imaging (fMRI) has transformed our understanding of the brain's functional organization. However, mapping subunits of a functional network using hemoglobin alone presents several disadvantages. Evoked and spontaneous hemodynamic fluctuations reflect ensemble activity from several populations of neurons making it difficult to discern excitatory vs inhibitory network activity. Still, blood-based methods of brain mapping remain powerful because hemoglobin provides endogenous contrast in all mammalian brains. To add greater specificity to hemoglobin assays, we integrated optical intrinsic signal(OIS) imaging with optogenetic stimulation to create an Opto-OIS mapping tool that combines the cell-specificity of optogenetics with label-free, hemoglobin imaging. Before mapping, titrated photostimuli determined which stimulus parameters elicited linear hemodynamic responses in the cortex. Optimized stimuli were then scanned over the left hemisphere to create a set of optogenetically-defined effective connectivity (Opto-EC) maps. For many sites investigated, Opto-EC maps exhibited higher spatial specificity than those determined using spontaneous hemodynamic fluctuations. For example, resting-state functional connectivity (RS-FC) patterns exhibited widespread ipsilateral connectivity while Opto-EC maps contained distinct short- and long-range constellations of ipsilateral connectivity. Further, RS-FC maps were usually symmetric about midline while Opto-EC maps displayed more heterogeneous contralateral homotopic connectivity. Both Opto-EC and RS-FC patterns were compared to mouse connectivity data from the Allen Institute. Unlike RS-FC maps, Thy1-based maps collected in awake, behaving mice closely recapitulated the connectivity structure derived using ex vivo anatomical tracer methods. Opto-OIS mapping could be a powerful tool for understanding cellular and molecular contributions to network dynamics and processing in the mouse brain.

  19. HCN channels segregate stimulation‐evoked movement responses in neocortex and allow for coordinated forelimb movements in rodents

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    Farrell, Jordan S.; Palmer, Laura A.; Singleton, Anna C.; Pittman, Quentin J.; Teskey, G. Campbell

    2016-01-01

    Key points The present study tested whether HCN channels contribute to the organization of motor cortex and to skilled motor behaviour during a forelimb reaching task.Experimental reductions in HCN channel signalling increase the representation of complex multiple forelimb movements in motor cortex as assessed by intracortical microstimulation.Global HCN1KO mice exhibit reduced reaching accuracy and atypical movements during a single‐pellet reaching task relative to wild‐type controls.Acute pharmacological inhibition of HCN channels in forelimb motor cortex decreases reaching accuracy and increases atypical movements during forelimb reaching. Abstract The mechanisms by which distinct movements of a forelimb are generated from the same area of motor cortex have remained elusive. Here we examined a role for HCN channels, given their ability to alter synaptic integration, in the expression of forelimb movement responses during intracortical microstimulation (ICMS) and movements of the forelimb on a skilled reaching task. We used short‐duration high‐resolution ICMS to evoke forelimb movements following pharmacological (ZD7288), experimental (electrically induced cortical seizures) or genetic approaches that we confirmed with whole‐cell patch clamp to substantially reduce I h current. We observed significant increases in the number of multiple movement responses evoked at single sites in motor maps to all three experimental manipulations in rats or mice. Global HCN1 knockout mice were less successful and exhibited atypical movements on a skilled‐motor learning task relative to wild‐type controls. Furthermore, in reaching‐proficient rats, reaching accuracy was reduced and forelimb movements were altered during infusion of ZD7288 within motor cortex. Thus, HCN channels play a critical role in the separation of overlapping movement responses and allow for successful reaching behaviours. These data provide a novel mechanism for the encoding of multiple

  20. Visual perception and frontal lobe in intellectual disabilities: a study with evoked potentials and neuropsychology.

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    Muñoz-Ruata, J; Caro-Martínez, E; Martínez Pérez, L; Borja, M

    2010-12-01

    Perception disorders are frequently observed in persons with intellectual disability (ID) and their influence on cognition has been discussed. The objective of this study is to clarify the mechanisms behind these alterations by analysing the visual event related potentials early component, the N1 wave, which is related to perception alterations in several pathologies. Additionally, the relationship between N1 and neuropsychological visual tests was studied with the aim to understand its functional significance in ID persons. A group of 69 subjects, with etiologically heterogeneous mild ID, performed an odd-ball task of active discrimination of geometric figures. N1a (frontal) and N1b (post-occipital) waves were obtained from the evoked potentials. They also performed several neuropsychological tests. Only component N1a, produced by the target stimulus, showed significant correlations with the visual integration, visual semantic association, visual analogical reasoning tests, Perceptual Reasoning Index (Wechsler Intelligence Scale for Children Fourth Edition) and intelligence quotient. The systematic correlations, produced by the target stimulus in perceptual abilities tasks, with the N1a (frontal) and not with N1b (posterior), suggest that the visual perception process involves frontal participation. These correlations support the idea that the N1a and N1b are not equivalent. The relationship between frontal functions and early stages of visual perception is revised and discussed, as well as the frontal contribution with the neuropsychological tests used. A possible relationship between the frontal activity dysfunction in ID and perceptive problems is suggested. Perceptive alteration observed in persons with ID could indeed be because of altered sensory areas, but also to a failure in the frontal participation of perceptive processes conceived as elaborations inside reverberant circuits of perception-action. © 2010 The Authors. Journal of Intellectual Disability

  1. Do ambient urban odors evoke basic emotions?

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    Sandra Theresia Weber-Glass

    2014-04-01

    Full Text Available Fragrances, such as plant odors, have been shown to evoke autonomic response patterns associated with Ekman’s (Ekman et al., 1983 basic emotions happiness, surprise, anger, fear, sadness and disgust. Inducing positive emotions by odors in highly frequented public spaces could serve to improve the quality of life in urban environments. Thus, the present study evaluated the potency of ambient odors connoted with an urban environment to evoke basic emotions on an autonomic and cognitive response level. Synthetic mixtures representing the odors of disinfectant, candles / bees wax, summer air, burnt smell, vomit and musty smell as well as odorless water as a control were presented five times in random order to 30 healthy, non-smoking human subjects with intact sense of smell. Skin temperature, skin conductance, breathing rate, forearm muscle activity, blink rate and heart rate were recorded simultaneously. Subjects rated the odors in terms of pleasantness, intensity and familiarity and gave verbal labels to each odor as well as cognitive associations with the basic emotions. The results showed that the amplitude of the skin conductance response varied as a function of odor presentation. Burnt smell and vomit elicited significantly higher electrodermal responses than summer air. Also, a negative correlation was revealed between the amplitude of the skin conductance response and hedonic odor valence indicating that the magnitude of the electrodermal response increased with odor unpleasantness. The analysis of the cognitive associations between odors and basic emotions showed that candles / bees wax and summer air were specifically associated with happiness whereas burnt smell and vomit were uniquely associated with disgust. Our findings suggest that city odors may evoke specific cognitive associations of basic emotions and that autonomic activity elicited by such odors is related to odor hedonics.

  2. Evoked Electromyographically Controlled Electrical Stimulation

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    Mitsuhiro Hayashibe

    2016-07-01

    Full Text Available Time-variant muscle responses under electrical stimulation (ES are often problematic for all the applications of neuroprosthetic muscle control. This situation limits the range of ES usage in relevant areas, mainly due to muscle fatigue and also to changes in stimulation electrode contact conditions, especially in transcutaneous ES. Surface electrodes are still the most widely used in noninvasive applications.Electrical field variations caused by changes in the stimulation contact condition markedly affect the resulting total muscle activation levels. Fatigue phenomena under functional electrical stimulation (FES are also well known source of time-varying characteristics coming from muscle response under ES. Therefore it is essential to monitor the actual muscle state and assess the expected muscle response by ES so as to improve the current ES system in favour of adaptive muscle-response-aware FES control. To deal with this issue, we have been studying a novel control technique using evoked electromyography (eEMG signals to compensate for these muscle time-variances under ES for stable neuroprosthetic muscle control. In this perspective article, I overview the background of this topic and highlight important points to be aware of when using ES to induce the desired muscle activation regardless of the time-variance. I also demonstrate how to deal with the common critical problem of ES to move toward robust neuroprosthetic muscle control with the Evoked Electromyographically Controlled Electrical Stimulation paradigm.

  3. Controlling a stream of paranoia evoking events in a virtual reality environment.

    Science.gov (United States)

    Isnanda, Reza Giga; Brinkman, Willem-Paul; Veling, Wim; van der Gaag, Mark; Neerincx, Mark

    2014-01-01

    Although virtual reality exposure has been reported as a method to induce paranoid thought, little is known about mechanisms to control specific virtual stressors. This paper reports on a study that examines the effect of controlling the stream of potential paranoia evoking events in a virtual restaurant world. A 2-by-2 experiment with a non-clinical group (n = 24) was conducted with as two within-subject factors: (1) the cycle time (short/long) for when the computer considers activation of a paranoia evoking event and (2) the probability that a paranoia-evoking event (low/high) would be triggered at the completion of a cycle. The results showed a significant main effect for the probability factor and two-way interaction effect with the cycle time factor on the number of paranoid comments participants made and their self-reported anxiety.

  4. Interaural difference values of vestibular evoked myogenic.

    Directory of Open Access Journals (Sweden)

    Marziyeh Moallemi

    2015-01-01

    Full Text Available Migraine is a neurologic disease, which often is associated with a unilateral headache. Vestibular abnormalities are common in migraine. Vestibular evoked myogenic potentials (VEMPs assess otolith function in particular functional integrity of the saccule and the inferior vestibular nerve. We used VEMP to evaluate if the migraine headache can affect VEMP asymmetry parameters. A total of 25 patients with migraine (22 females and 3 males who were diagnosed according to the criteria of IHS-1988 were enrolled in this cross-sectional study. Control group consisted of 26 healthy participants (18 female and 8 male, without neurotological symptoms and history of migraine. The short tone burst (95 dB nHL, 500 Hz was presented to ears. VEMP was recorded with surface electromyography over the contracted ipsilateral sternocleidomastoid (SCM muscle. Although current results showed that the amplitude ratio is greater in migraine patients than normal group, there was no statistical difference between two groups in mean asymmetry parameters of VEMP. Asymmetry measurements in vestibular evoked myogenic potentials probably are not indicators of unilateral deficient in saccular pathways of migraine patients.

  5. Associative learning in humans--conditioning of sensory-evoked brain activity.

    Science.gov (United States)

    Skrandies, W; Jedynak, A

    2000-01-01

    A classical conditioning paradigm was employed in two experiments performed on 35 human volunteers. In nine subjects, the presentation of Landolt rings (conditioned stimuli, CS + ) was paired with an electric stimulus (unconditioned stimuli, UCS) applied to the left median nerve. Neutral visual control stimuli were full circles (CS -) that were not paired with the UCS. The skin conductance response (SCR) was determined in a time interval of 5 s after onset of the visual stimuli, and it was measured in the acquisition and test phase. Associative learning was reflected by a SCR occurring selectively with CS +. The same experiment was repeated with another group of 26 adults while electroencephalogram (EEG) was recorded from 30 electrodes. For each subject, mean evoked potentials were computed. In 13 of the subjects, a conditioning paradigm was followed while the other subjects served as the control group (non-contingent stimulation). There were somatosensory and visual brain activity evoked by the stimuli. Conditioned components were identified by computing cross-correlation between evoked somatosensory components and the averaged EEG. In the visual evoked brain activity, three components with mean latencies of 105.4, 183.2, and 360.3 ms were analyzed. Somatosensory stimuli were followed by major components that occurred at mean latencies of 48.8, 132.5, 219.7, 294.8, and 374.2 ms latency after the shock. All components were analyzed in terms of latency, field strength, and topographic characteristics, and were compared between groups and experimental conditions. Both visual and somatosensory brain activity was significantly affected by classical conditioning. Our data illustrate how associative learning affects the topography of brain electrical activity elicited by presentation of conditioned visual stimuli.

  6. ATM and ATR play complementary roles in the behavior of excitatory and inhibitory vesicle populations.

    Science.gov (United States)

    Cheng, Aifang; Zhao, Teng; Tse, Kai-Hei; Chow, Hei-Man; Cui, Yong; Jiang, Liwen; Du, Shengwang; Loy, Michael M T; Herrup, Karl

    2018-01-09

    ATM (ataxia-telangiectasia mutated) and ATR (ATM and Rad3-related) are large PI3 kinases whose human mutations result in complex syndromes that include a compromised DNA damage response (DDR) and prominent nervous system phenotypes. Both proteins are nuclear-localized in keeping with their DDR functions, yet both are also found in cytoplasm, including on neuronal synaptic vesicles. In ATM- or ATR-deficient neurons, spontaneous vesicle release is reduced, but a drop in ATM or ATR level also slows FM4-64 dye uptake. In keeping with this, both proteins bind to AP-2 complex components as well as to clathrin, suggesting roles in endocytosis and vesicle recycling. The two proteins play complementary roles in the DDR; ATM is engaged in the repair of double-strand breaks, while ATR deals mainly with single-strand damage. Unexpectedly, this complementarity extends to these proteins' synaptic function as well. Superresolution microscopy and coimmunoprecipitation reveal that ATM associates exclusively with excitatory (VGLUT1 + ) vesicles, while ATR associates only with inhibitory (VGAT + ) vesicles. The levels of ATM and ATR respond to each other; when ATM is deficient, ATR levels rise, and vice versa. Finally, blocking NMDA, but not GABA, receptors causes ATM levels to rise while ATR levels respond to GABA, but not NMDA, receptor blockade. Taken together, our data suggest that ATM and ATR are part of the cellular "infrastructure" that maintains the excitatory/inhibitory balance of the nervous system. This idea has important implications for the human diseases resulting from their genetic deficiency.

  7. Resting-state hemodynamics are spatiotemporally coupled to synchronized and symmetric neural activity in excitatory neurons

    Science.gov (United States)

    Ma, Ying; Shaik, Mohammed A.; Kozberg, Mariel G.; Portes, Jacob P.; Timerman, Dmitriy

    2016-01-01

    Brain hemodynamics serve as a proxy for neural activity in a range of noninvasive neuroimaging techniques including functional magnetic resonance imaging (fMRI). In resting-state fMRI, hemodynamic fluctuations have been found to exhibit patterns of bilateral synchrony, with correlated regions inferred to have functional connectivity. However, the relationship between resting-state hemodynamics and underlying neural activity has not been well established, making the neural underpinnings of functional connectivity networks unclear. In this study, neural activity and hemodynamics were recorded simultaneously over the bilateral cortex of awake and anesthetized Thy1-GCaMP mice using wide-field optical mapping. Neural activity was visualized via selective expression of the calcium-sensitive fluorophore GCaMP in layer 2/3 and 5 excitatory neurons. Characteristic patterns of resting-state hemodynamics were accompanied by more rapidly changing bilateral patterns of resting-state neural activity. Spatiotemporal hemodynamics could be modeled by convolving this neural activity with hemodynamic response functions derived through both deconvolution and gamma-variate fitting. Simultaneous imaging and electrophysiology confirmed that Thy1-GCaMP signals are well-predicted by multiunit activity. Neurovascular coupling between resting-state neural activity and hemodynamics was robust and fast in awake animals, whereas coupling in urethane-anesthetized animals was slower, and in some cases included lower-frequency (resting-state hemodynamics in the awake and anesthetized brain are coupled to underlying patterns of excitatory neural activity. The patterns of bilaterally-symmetric spontaneous neural activity revealed by wide-field Thy1-GCaMP imaging may depict the neural foundation of functional connectivity networks detected in resting-state fMRI. PMID:27974609

  8. Evidence that 5-hydroxytryptamine/sub 3/ receptors mediate cytotoxic drug and radiation-evoked emesis

    Energy Technology Data Exchange (ETDEWEB)

    Miner, W.D.; Sanger, G.J.; Turner, D.H.

    1987-08-01

    The involvement of 5-hydroxytryptamine (5-HT) 5-HT/sub 3/ receptors in the mechanisms of severe emesis evoked by cytotoxic drugs or by total body irradiation have been studied in ferrets. Anti-emetic compounds tested were domperidone (a dopamine antagonist), metoclopramide (a gastric motility stimulant and dopamine antagonist at conventional doses, a 5-HT/sub 3/ receptor antagonist at higher doses) and BRL 24924 (a potent gastric motility stimulant and a 5-HT/sub 3/ receptor antagonist). Domperidone or metoclopramide prevented apomorphine-evoked emesis, whereas BRL 24924 did not. Similar doses of domperidone did not prevent emesis evoked by cis-platin or by total body irradiation, whereas metoclopramide or BRL 24924 greatly reduced or prevented these types of emesis. Metoclopramide and BRL 24924 also prevented emesis evoked by a combination of doxorubicin and cyclophosphamide. These results are discussed in terms of a fundamental role for 5-HT/sub 3/ receptors in the mechanisms mediating severely emetogenic cancer treatment therapies.

  9. Loss of Local Astrocyte Support Disrupts Action Potential Propagation and Glutamate Release Synchrony from Unmyelinated Hippocampal Axon Terminals In Vitro.

    Science.gov (United States)

    Sobieski, Courtney; Jiang, Xiaoping; Crawford, Devon C; Mennerick, Steven

    2015-08-05

    Neuron-astrocyte interactions are critical for proper CNS development and function. Astrocytes secrete factors that are pivotal for synaptic development and function, neuronal metabolism, and neuronal survival. Our understanding of this relationship, however, remains incomplete due to technical hurdles that have prevented the removal of astrocytes from neuronal circuits without changing other important conditions. Here we overcame this obstacle by growing solitary rat hippocampal neurons on microcultures that were comprised of either an astrocyte bed (+astrocyte) or a collagen bed (-astrocyte) within the same culture dish. -Astrocyte autaptic evoked EPSCs, but not IPSCs, displayed an altered temporal profile, which included increased synaptic delay, increased time to peak, and severe glutamate release asynchrony, distinct from previously described quantal asynchrony. Although we observed minimal alteration of the somatically recorded action potential waveform, action potential propagation was altered. We observed a longer latency between somatic initiation and arrival at distal locations, which likely explains asynchronous EPSC peaks, and we observed broadening of the axonal spike, which likely underlies changes to evoked EPSC onset. No apparent changes in axon structure were observed, suggesting altered axonal excitability. In conclusion, we propose that local astrocyte support has an unappreciated role in maintaining glutamate release synchrony by disturbing axonal signal propagation. Certain glial cell types (oligodendrocytes, Schwann cells) facilitate the propagation of neuronal electrical signals, but a role for astrocytes has not been identified despite many other functions of astrocytes in supporting and modulating neuronal signaling. Under identical global conditions, we cultured neurons with or without local astrocyte support. Without local astrocytes, glutamate transmission was desynchronized by an alteration of the waveform and arrival time of axonal

  10. Nutritional State-Dependent Ghrelin Activation of Vasopressin Neurons via Retrograde Trans-Neuronal–Glial Stimulation of Excitatory GABA Circuits

    Science.gov (United States)

    Haam, Juhee; Halmos, Katalin C.; Di, Shi

    2014-01-01

    Behavioral and physiological coupling between energy balance and fluid homeostasis is critical for survival. The orexigenic hormone ghrelin has been shown to stimulate the secretion of the osmoregulatory hormone vasopressin (VP), linking nutritional status to the control of blood osmolality, although the mechanism of this systemic crosstalk is unknown. Here, we show using electrophysiological recordings and calcium imaging in rat brain slices that ghrelin stimulates VP neurons in the hypothalamic paraventricular nucleus (PVN) in a nutritional state-dependent manner by activating an excitatory GABAergic synaptic input via a retrograde neuronal–glial circuit. In slices from fasted rats, ghrelin activation of a postsynaptic ghrelin receptor, the growth hormone secretagogue receptor type 1a (GHS-R1a), in VP neurons caused the dendritic release of VP, which stimulated astrocytes to release the gliotransmitter adenosine triphosphate (ATP). ATP activation of P2X receptors excited presynaptic GABA neurons to increase GABA release, which was excitatory to the VP neurons. This trans-neuronal–glial retrograde circuit activated by ghrelin provides an alternative means of stimulation of VP release and represents a novel mechanism of neuronal control by local neuronal–glial circuits. It also provides a potential cellular mechanism for the physiological integration of energy and fluid homeostasis. PMID:24790191

  11. Up-Regulation of the Excitatory Amino Acid Transporters EAAT1 and EAAT2 by Mammalian Target of Rapamycin

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    Abeer Abousaab

    2016-11-01

    Full Text Available Background: The excitatory amino-acid transporters EAAT1 and EAAT2 clear glutamate from the synaptic cleft and thus terminate neuronal excitation. The carriers are subject to regulation by various kinases. The EAAT3 isoform is regulated by mammalian target of rapamycin (mTOR. The present study thus explored whether mTOR influences transport by EAAT1 and/or EAAT2. Methods: cRNA encoding wild type EAAT1 (SLC1A3 or EAAT2 (SLC1A2 was injected into Xenopus oocytes without or with additional injection of cRNA encoding mTOR. Dual electrode voltage clamp was performed in order to determine electrogenic glutamate transport (IEAAT. EAAT2 protein abundance was determined utilizing chemiluminescence. Results: Appreciable IEAAT was observed in EAAT1 or EAAT2 expressing but not in water injected oocytes. IEAAT was significantly increased by coexpression of mTOR. Coexpression of mTOR increased significantly the maximal IEAAT in EAAT1 or EAAT2 expressing oocytes, without significantly modifying affinity of the carriers. Moreover, coexpression of mTOR increased significantly EAAT2 protein abundance in the cell membrane. Conclusions: The kinase mTOR up-regulates the excitatory amino acid transporters EAAT1 and EAAT2.

  12. Comparison of burrowing and stimuli-evoked pain behaviors as end-points in rat models of inflammatory pain and peripheral neuropathic pain

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    Arjun eMuralidharan

    2016-05-01

    Full Text Available Establishment and validation of ethologically-relevant, non-evoked behavioral end-points as surrogate measures of spontaneous pain in rodent pain models has been proposed as a means to improve preclinical to clinical research translation in the pain field. Here, we compared the utility of burrowing behavior with hypersensitivity to applied mechanical stimuli for pain assessment in rat models of chronic inflammatory and peripheral neuropathic pain. Briefly, groups of male Sprague-Dawley rats were habituated to the burrowing environment and trained over a 5-day period. Rats that burrowed ≤450g of gravel on any two days of the individual training phase were excluded from the study. The remaining rats received either a unilateral intraplantar injection of Freund’s complete adjuvant (FCA or saline, or underwent unilateral chronic constriction injury (CCI of the sciatic nerve- or sham-surgery. Baseline burrowing behavior and evoked pain behaviors were assessed prior to model induction, and twice-weekly until study completion on day 14. For FCA- and CCI-rats, but not the corresponding groups of sham-rats, evoked mechanical hypersensitivity developed in a temporal manner in the ipsilateral hindpaws. Although burrowing behavior also decreased in a temporal manner for both FCA- and CCI-rats, there was considerable inter-animal variability. By contrast, mechanical hyperalgesia and mechanical allodynia in the ipsilateral hindpaws of FCA- and CCI-rats respectively, exhibited minimal inter-animal variability. Our data collectively show that burrowing behavior is altered in rodent models of chronic inflammatory pain and peripheral neuropathic pain. However, large group sizes are needed to ensure studies are adequately powered due to considerable inter-animal variability.

  13. Locally excitatory, globally inhibitory oscillator networks: theory and application to scene segmentation

    Science.gov (United States)

    Wang, DeLiang; Terman, David

    1995-01-01

    A novel class of locally excitatory, globally inhibitory oscillator networks (LEGION) is proposed and investigated analytically and by computer simulation. The model of each oscillator corresponds to a standard relaxation oscillator with two time scales. The network exhibits a mechanism of selective gating, whereby an oscillator jumping up to its active phase rapidly recruits the oscillators stimulated by the same pattern, while preventing other oscillators from jumping up. We show analytically that with the selective gating mechanism the network rapidly achieves both synchronization within blocks of oscillators that are stimulated by connected regions and desynchronization between different blocks. Computer simulations demonstrate LEGION's promising ability for segmenting multiple input patterns in real time. This model lays a physical foundation for the oscillatory correlation theory of feature binding, and may provide an effective computational framework for scene segmentation and figure/ground segregation.

  14. Musical Brains. A study of evoked musical sensations without external auditory stimuli. Preliminary report of three cases

    International Nuclear Information System (INIS)

    Goycoolea, Marcos V; Mena, Ismael; Neubauer, Sonia G; Levy, Raquel G.; Fernandez Grez, Margarita; Berger, Claudia G

    2006-01-01

    Background: There are individuals, usually musicians, who are seemingly able to evoke musical sensations without external auditory stimuli. However, to date there is no available evidence to determine if it is feasible to have musical sensations without using external sensory receptors nor if there is a biological substrate to these sensations. Study design: Two single photon emission computerized tomography (SPECT) evaluations with [99mTc]-HMPAO were conducted in each of three female musicians. One was done under basal conditions (without evoking) and the other one while evoking these sensations. Results: In the NeuroSPECT studies of the musicians who were tested while evoking a musical composition, there was a significant increase in perfusion above the normal mean in the right and left hemispheres in Brodmann's areas 9 and 8 (frontal executive area) and in areas 40 on the left side (auditory center). However, under basal conditions there was no hyper perfusion of areas 9, 8, 39 and 40. In one case hyper perfusion was found under basal conditions in area 45, however it was less than when she was evoking. Conclusions: These findings are suggestive of a biological substrate to the process of evoking musical sensations (au)

  15. Training Excitatory-Inhibitory Recurrent Neural Networks for Cognitive Tasks: A Simple and Flexible Framework.

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    H Francis Song

    2016-02-01

    Full Text Available The ability to simultaneously record from large numbers of neurons in behaving animals has ushered in a new era for the study of the neural circuit mechanisms underlying cognitive functions. One promising approach to uncovering the dynamical and computational principles governing population responses is to analyze model recurrent neural networks (RNNs that have been optimized to perform the same tasks as behaving animals. Because the optimization of network parameters specifies the desired output but not the manner in which to achieve this output, "trained" networks serve as a source of mechanistic hypotheses and a testing ground for data analyses that link neural computation to behavior. Complete access to the activity and connectivity of the circuit, and the ability to manipulate them arbitrarily, make trained networks a convenient proxy for biological circuits and a valuable platform for theoretical investigation. However, existing RNNs lack basic biological features such as the distinction between excitatory and inhibitory units (Dale's principle, which are essential if RNNs are to provide insights into the operation of biological circuits. Moreover, trained networks can achieve the same behavioral performance but differ substantially in their structure and dynamics, highlighting the need for a simple and flexible framework for the exploratory training of RNNs. Here, we describe a framework for gradient descent-based training of excitatory-inhibitory RNNs that can incorporate a variety of biological knowledge. We provide an implementation based on the machine learning library Theano, whose automatic differentiation capabilities facilitate modifications and extensions. We validate this framework by applying it to well-known experimental paradigms such as perceptual decision-making, context-dependent integration, multisensory integration, parametric working memory, and motor sequence generation. Our results demonstrate the wide range of neural

  16. Training Excitatory-Inhibitory Recurrent Neural Networks for Cognitive Tasks: A Simple and Flexible Framework

    Science.gov (United States)

    Wang, Xiao-Jing

    2016-01-01

    The ability to simultaneously record from large numbers of neurons in behaving animals has ushered in a new era for the study of the neural circuit mechanisms underlying cognitive functions. One promising approach to uncovering the dynamical and computational principles governing population responses is to analyze model recurrent neural networks (RNNs) that have been optimized to perform the same tasks as behaving animals. Because the optimization of network parameters specifies the desired output but not the manner in which to achieve this output, “trained” networks serve as a source of mechanistic hypotheses and a testing ground for data analyses that link neural computation to behavior. Complete access to the activity and connectivity of the circuit, and the ability to manipulate them arbitrarily, make trained networks a convenient proxy for biological circuits and a valuable platform for theoretical investigation. However, existing RNNs lack basic biological features such as the distinction between excitatory and inhibitory units (Dale’s principle), which are essential if RNNs are to provide insights into the operation of biological circuits. Moreover, trained networks can achieve the same behavioral performance but differ substantially in their structure and dynamics, highlighting the need for a simple and flexible framework for the exploratory training of RNNs. Here, we describe a framework for gradient descent-based training of excitatory-inhibitory RNNs that can incorporate a variety of biological knowledge. We provide an implementation based on the machine learning library Theano, whose automatic differentiation capabilities facilitate modifications and extensions. We validate this framework by applying it to well-known experimental paradigms such as perceptual decision-making, context-dependent integration, multisensory integration, parametric working memory, and motor sequence generation. Our results demonstrate the wide range of neural activity

  17. Serotonin increases synaptic activity in olfactory bulb glomeruli.

    Science.gov (United States)

    Brill, Julia; Shao, Zuoyi; Puche, Adam C; Wachowiak, Matt; Shipley, Michael T

    2016-03-01

    Serotoninergic fibers densely innervate olfactory bulb glomeruli, the first sites of synaptic integration in the olfactory system. Acting through 5HT2A receptors, serotonin (5HT) directly excites external tufted cells (ETCs), key excitatory glomerular neurons, and depolarizes some mitral cells (MCs), the olfactory bulb's main output neurons. We further investigated 5HT action on MCs and determined its effects on the two major classes of glomerular interneurons: GABAergic/dopaminergic short axon cells (SACs) and GABAergic periglomerular cells (PGCs). In SACs, 5HT evoked a depolarizing current mediated by 5HT2C receptors but did not significantly impact spike rate. 5HT had no measurable direct effect in PGCs. Serotonin increased spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) in PGCs and SACs. Increased sEPSCs were mediated by 5HT2A receptors, suggesting that they are primarily due to enhanced excitatory drive from ETCs. Increased sIPSCs resulted from elevated excitatory drive onto GABAergic interneurons and augmented GABA release from SACs. Serotonin-mediated GABA release from SACs was action potential independent and significantly increased miniature IPSC frequency in glomerular neurons. When focally applied to a glomerulus, 5HT increased MC spontaneous firing greater than twofold but did not increase olfactory nerve-evoked responses. Taken together, 5HT modulates glomerular network activity in several ways: 1) it increases ETC-mediated feed-forward excitation onto MCs, SACs, and PGCs; 2) it increases inhibition of glomerular interneurons; 3) it directly triggers action potential-independent GABA release from SACs; and 4) these network actions increase spontaneous MC firing without enhancing responses to suprathreshold sensory input. This may enhance MC sensitivity while maintaining dynamic range. Copyright © 2016 the American Physiological Society.

  18. Nostalgia-Evoked Inspiration: Mediating Mechanisms and Motivational Implications.

    Science.gov (United States)

    Stephan, Elena; Sedikides, Constantine; Wildschut, Tim; Cheung, Wing-Yee; Routledge, Clay; Arndt, Jamie

    2015-10-01

    Six studies examined the nostalgia-inspiration link and its motivational implications. In Study 1, nostalgia proneness was positively associated with inspiration frequency and intensity. In Studies 2 and 3, the recollection of nostalgic (vs. ordinary) experiences increased both general inspiration and specific inspiration to engage in exploratory activities. In Study 4, serial mediational analyses supported a model in which nostalgia increases social connectedness, which subsequently fosters self-esteem, which then boosts inspiration. In Study 5, a rigorous evaluation of this serial mediational model (with a novel nostalgia induction controlling for positive affect) reinforced the idea that nostalgia-elicited social connectedness increases self-esteem, which then heightens inspiration. Study 6 extended the serial mediational model by demonstrating that nostalgia-evoked inspiration predicts goal pursuit (intentions to pursue an important goal). Nostalgia spawns inspiration via social connectedness and attendant self-esteem. In turn, nostalgia-evoked inspiration bolsters motivation. © 2015 by the Society for Personality and Social Psychology, Inc.

  19. 5-HT2A receptor deficiency alters the metabolic and transcriptional, but not the behavioral, consequences of chronic unpredictable stress

    Directory of Open Access Journals (Sweden)

    Minal Jaggar

    2017-12-01

    Full Text Available Chronic stress enhances risk for psychiatric disorders, and in animal models is known to evoke depression-like behavior accompanied by perturbed neurohormonal, metabolic, neuroarchitectural and transcriptional changes. Serotonergic neurotransmission, including serotonin2A (5-HT2A receptors, have been implicated in mediating specific aspects of stress-induced responses. Here we investigated the influence of chronic unpredictable stress (CUS on depression-like behavior, serum metabolic measures, and gene expression in stress-associated neurocircuitry of the prefrontal cortex (PFC and hippocampus in 5-HT2A receptor knockout (5-HT2A−/− and wild-type mice of both sexes. While 5-HT2A−/− male and female mice exhibited a baseline reduced anxiety-like state, this did not alter the onset or severity of behavioral despair during and at the cessation of CUS, indicating that these mice can develop stress-evoked depressive behavior. Analysis of metabolic parameters in serum revealed a CUS-evoked dyslipidemia, which was abrogated in 5-HT2A−/− female mice with a hyperlipidemic baseline phenotype. 5-HT2A−/− male mice in contrast did not exhibit such a baseline shift in their serum lipid profile. Specific stress-responsive genes (Crh, Crhr1, Nr3c1, and Nr3c2, trophic factors (Bdnf, Igf1 and immediate early genes (IEGs (Arc, Fos, Fosb, Egr1-4 in the PFC and hippocampus were altered in 5-HT2A−/− mice both under baseline and CUS conditions. Our results support a role for the 5-HT2A receptor in specific metabolic and transcriptional, but not behavioral, consequences of CUS, and highlight that the contribution of the 5-HT2A receptor to stress-evoked changes is sexually dimorphic. Keywords: 5-HT2A−/− mice, Prefrontal cortex, Hippocampus, Gene expression, Sexual dimorphism, Despair

  20. Fetal MEG evoked response latency from beamformer with random field theory.

    Science.gov (United States)

    McCubbin, J; Vrba, J; Murphy, P; Temple, J; Eswaran, H; Lowery, C L; Preissl, H

    2010-01-01

    Analysis of fetal magnetoencephalographic brain recordings is restricted by low signal to noise ratio (SNR) and non-stationarity of the sources. Beamformer techniques have been applied to improve SNR of fetal evoked responses. However, until now the effect of non-stationarity was not taken into account in detail, because the detection of evoked responses is in most cases determined by averaging a large number of trials. We applied a windowing technique to improve the stationarity of the data by using short time segments recorded during a flash-evoked study. In addition, we implemented a random field theory approach for more stringent control of false-positives in the statistical parametric map of the search volume for the beamformer. The search volume was based on detailed individual fetal/maternal biometrics from ultrasound scans and fetal heart localization. Average power over a sliding window within the averaged evoked response against a randomized average background power was used as the test z-statistic. The significance threshold was set at 10% over all members of a contiguous cluster of voxels. There was at least one significant response for 62% of fetal and 95% of newborn recordings with gestational age (GA) between 28 and 45 weeks from 29 subjects. We found that the latency was either substantially unchanged or decreased with increasing GA for most subjects, with a nominal rate of about -11 ms/week. These findings support the anticipated neurophysiological development, provide validation for the beamformer model search as a methodology, and may lead to a clinical test for fetal cognitive development.

  1. Plasticity of Hippocampal Excitatory-Inhibitory Balance: Missing the Synaptic Control in the Epileptic Brain

    Directory of Open Access Journals (Sweden)

    Christian Bonansco

    2016-01-01

    Full Text Available Synaptic plasticity is the capacity generated by experience to modify the neural function and, thereby, adapt our behaviour. Long-term plasticity of glutamatergic and GABAergic transmission occurs in a concerted manner, finely adjusting the excitatory-inhibitory (E/I balance. Imbalances of E/I function are related to several neurological diseases including epilepsy. Several evidences have demonstrated that astrocytes are able to control the synaptic plasticity, with astrocytes being active partners in synaptic physiology and E/I balance. Here, we revise molecular evidences showing the epileptic stage as an abnormal form of long-term brain plasticity and propose the possible participation of astrocytes to the abnormal increase of glutamatergic and decrease of GABAergic neurotransmission in epileptic networks.

  2. Interactions of MK-801 with glutamate-, glutamine- and methamphetamine-evoked release of [3H]dopamine from striatal slices

    International Nuclear Information System (INIS)

    Bowyer, J.F.; Scallet, A.C.; Holson, R.R.; Lipe, G.W.; Slikker, W. Jr.; Ali, S.F.

    1991-01-01

    The interactions of MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine], glutamate and glutamine with methamphetamine (METH)-evoked release of [ 3 H]dopamine were assessed in vitro to determine whether MK-801 inhibition of METH neurotoxicity might be mediated presynaptically, and to evaluate the effects of glutamatergic stimulation on METH-evoked dopamine release. MK-801 inhibition of glutamate- or METH-evoked dopamine release might reduce synaptic dopamine levels during METH exposure and decrease the formation of 6-hydroxydopamine or other related neurotoxins. Without Mg 2+ present, 40 microM and 1 mM glutamate evoked a N-methyl-D-aspartate receptor-mediated [ 3 H]dopamine and [ 3 H]metabolite (tritium) release of 3 to 6 and 12 to 16% of total tritium stores, respectively, from striatal slices. With 1.50 mM Mg 2+ present, 10 mM glutamate alone or in combination with the dopamine uptake blocker nomifensine released only 2.1 or 4.2%, respectively, of total tritium stores, and release was only partially dependent on N-methyl-D-aspartate-type glutamate receptors. With or without 1.50 mM Mg 2+ present, 0.5 or 5 microM METH evoked a substantial release of tritium (5-8 or 12-21% of total stores, respectively). METH-evoked dopamine release was not affected by 5 microM MK-801 but METH-evoked release was additive with glutamate-evoked release. Without Mg 2+ present, 1 mM glutamine increased glutamate release and induced the release of [ 3 H]dopamine and metabolites. Both 0.5 and 5 microM METH also increased tritium release with 1 mM glutamine present. When striatal slices were exposed to 5 microM METH this glutamine-evoked release of glutamate was increased more than 50%

  3. Influence of detomidine and buprenorphine on motor-evoked potentials in horses.

    Science.gov (United States)

    Nollet, H; Van Ham, L; Gasthuys, F; Dewulf, J; Vanderstraeten, G; Deprez, P

    2003-04-26

    Horses need to be sedated before they are investigated by transcranial magnetic stimulation because of the mild discomfort induced by the evoked muscle contraction and the noise of stimulation. This paper describes the influence of a combination of detomidine (10 microg/kg bodyweight) and a low dose of buprenorphine (2.4 microg/kg) on the onset latency and peak-to-peak amplitude of magnetic motor-evoked potentials in normal horses. There were no significant differences between measurements of these parameters made before the horses were sedated and measurements made 10 and 30 minutes after the drugs were administered.

  4. From Nose to Memory: The Involuntary Nature of Odor-evoked Autobiographical Memories in Alzheimer's Disease.

    Science.gov (United States)

    El Haj, Mohamad; Gandolphe, Marie Charlotte; Gallouj, Karim; Kapogiannis, Dimitrios; Antoine, Pascal

    2017-12-25

    Research suggests that odors may serve as a potent cue for autobiographical retrieval. We tested this hypothesis in Alzheimer's disease (AD) and investigated whether odor-evoked autobiographical memory is an involuntary process that shares similarities with music-evoked autobiographical memory. Participants with mild AD and controls were asked to retrieve 2 personal memories after odor exposure, after music exposure, and in an odor-and music-free condition. AD participants showed better specificity, emotional experience, mental time travel, and retrieval time after odor and music exposure than in the control condition. Similar beneficial effects of odor and music exposure were observed for autobiographical characteristics (i.e., specificity, emotional experience, and mental time travel), except for retrieval time which was more improved after odor than after music exposure. Interestingly, regression analyses suggested executive involvement in memories evoked in the control condition but not in those evoked after music or odor exposure. These findings suggest the involuntary nature of odor-evoked autobiographical memory in AD. They also suggest that olfactory cuing could serve as a useful and ecologically valid tool to stimulate autobiographical memory, at least in the mild stage of the disease. © The Author(s) 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Newborn hearing screening with transient evoked otoacoustic emissions and automatic auditory brainstem response

    OpenAIRE

    Renata Mota Mamede de Carvallo; Carla Gentile Matas; Isabela de Souza Jardim

    2008-01-01

    Objective: The aim of the present investigation was to check Transient Evoked Otoacoustic Emissions and Automatic Auditory Brainstem Response tests applied together in regular nurseries and Newborn Intensive Care Units (NICU), as well as to describe and compare the results obtained in both groups. Methods: We tested 150 newborns from regular nurseries and 70 from NICU. Rresults: The newborn hearing screening results using Transient Evoked Otoacoustic Emissions and Automatic Auditory Brainstem...

  6. Somatodendritic and excitatory postsynaptic distribution of neuron-type dystrophin isoform, Dp40, in hippocampal neurons

    Energy Technology Data Exchange (ETDEWEB)

    Fujimoto, Takahiro; Itoh, Kyoko, E-mail: kxi14@koto.kpu-m.ac.jp; Yaoi, Takeshi; Fushiki, Shinji

    2014-09-12

    Highlights: • Identification of dystrophin (Dp) shortest isoform, Dp40, is a neuron-type Dp. • Dp40 expression is temporally and differentially regulated in comparison to Dp71. • Somatodendritic and nuclear localization of Dp40. • Dp40 is localized to excitatory postsynapses. • Dp40 might play roles in dendritic and synaptic functions. - Abstract: The Duchenne muscular dystrophy (DMD) gene produces multiple dystrophin (Dp) products due to the presence of several promoters. We previously reported the existence of a novel short isoform of Dp, Dp40, in adult mouse brain. However, the exact biochemical expression profile and cytological distribution of the Dp40 protein remain unknown. In this study, we generated a polyclonal antibody against the NH{sub 2}-terminal region of the Dp40 and identified the expression profile of Dp40 in the mouse brain. Through an analysis using embryonic and postnatal mouse cerebrums, we found that Dp40 emerged from the early neonatal stages until adulthood, whereas Dp71, an another Dp short isoform, was highly detected in both prenatal and postnatal cerebrums. Intriguingly, relative expressions of Dp40 and Dp71 were prominent in cultured dissociated neurons and non-neuronal cells derived from mouse hippocampus, respectively. Furthermore, the immunocytological distribution of Dp40 was analyzed in dissociated cultured neurons, revealing that Dp40 is detected in the soma and its dendrites, but not in the axon. It is worthy to note that Dp40 is localized along the subplasmalemmal region of the dendritic shafts, as well as at excitatory postsynaptic sites. Thus, Dp40 was identified as a neuron-type Dp possibly involving dendritic and synaptic functions.

  7. Somatodendritic and excitatory postsynaptic distribution of neuron-type dystrophin isoform, Dp40, in hippocampal neurons

    International Nuclear Information System (INIS)

    Fujimoto, Takahiro; Itoh, Kyoko; Yaoi, Takeshi; Fushiki, Shinji

    2014-01-01

    Highlights: • Identification of dystrophin (Dp) shortest isoform, Dp40, is a neuron-type Dp. • Dp40 expression is temporally and differentially regulated in comparison to Dp71. • Somatodendritic and nuclear localization of Dp40. • Dp40 is localized to excitatory postsynapses. • Dp40 might play roles in dendritic and synaptic functions. - Abstract: The Duchenne muscular dystrophy (DMD) gene produces multiple dystrophin (Dp) products due to the presence of several promoters. We previously reported the existence of a novel short isoform of Dp, Dp40, in adult mouse brain. However, the exact biochemical expression profile and cytological distribution of the Dp40 protein remain unknown. In this study, we generated a polyclonal antibody against the NH 2 -terminal region of the Dp40 and identified the expression profile of Dp40 in the mouse brain. Through an analysis using embryonic and postnatal mouse cerebrums, we found that Dp40 emerged from the early neonatal stages until adulthood, whereas Dp71, an another Dp short isoform, was highly detected in both prenatal and postnatal cerebrums. Intriguingly, relative expressions of Dp40 and Dp71 were prominent in cultured dissociated neurons and non-neuronal cells derived from mouse hippocampus, respectively. Furthermore, the immunocytological distribution of Dp40 was analyzed in dissociated cultured neurons, revealing that Dp40 is detected in the soma and its dendrites, but not in the axon. It is worthy to note that Dp40 is localized along the subplasmalemmal region of the dendritic shafts, as well as at excitatory postsynaptic sites. Thus, Dp40 was identified as a neuron-type Dp possibly involving dendritic and synaptic functions

  8. Kindling-induced potentiation of excitatory and inhibitory inputs to hippocampal dentate granule cells. II. Effects of the NMDA antagonist MK-801.

    LENUS (Irish Health Repository)

    Robinson, G B

    1991-10-18

    The effect of the non-competitive N-methyl-D-aspartate antagonist MK-801 on the early development of kindling-induced potentiation was examined in the rabbit hippocampal dentate gyrus. MK-801 (0.5 mg\\/kg) was administered 2 h before each daily kindling stimulation was applied to the perforant path. This treatment continued for the first 10 days of kindling. MK-801 depressed the growth of the afterdischarge duration and suppressed development of behavioral seizures. MK-801 did not block kindling-induced potentiation of either the perforant path-dentate granule cell population spike or excitatory postsynaptic potential. Random impulse train stimulation and non-linear systems analytic techniques were used to examine kindling-induced potentiation of presumed GABAergic recurrent inhibitory circuits. Both the magnitude and duration of kindling-induced response inhibition, to the second of each pair of impulses within the train, were reduced in rabbits pretreated with MK-801. These results suggest that MK-801 differentially affects kindling-induced potentiation of excitatory and inhibitory circuits within the rabbit hippocampal dentate gyrus.

  9. Speech Evoked Auditory Brainstem Response in Stuttering

    Directory of Open Access Journals (Sweden)

    Ali Akbar Tahaei

    2014-01-01

    Full Text Available Auditory processing deficits have been hypothesized as an underlying mechanism for stuttering. Previous studies have demonstrated abnormal responses in subjects with persistent developmental stuttering (PDS at the higher level of the central auditory system using speech stimuli. Recently, the potential usefulness of speech evoked auditory brainstem responses in central auditory processing disorders has been emphasized. The current study used the speech evoked ABR to investigate the hypothesis that subjects with PDS have specific auditory perceptual dysfunction. Objectives. To determine whether brainstem responses to speech stimuli differ between PDS subjects and normal fluent speakers. Methods. Twenty-five subjects with PDS participated in this study. The speech-ABRs were elicited by the 5-formant synthesized syllable/da/, with duration of 40 ms. Results. There were significant group differences for the onset and offset transient peaks. Subjects with PDS had longer latencies for the onset and offset peaks relative to the control group. Conclusions. Subjects with PDS showed a deficient neural timing in the early stages of the auditory pathway consistent with temporal processing deficits and their abnormal timing may underlie to their disfluency.

  10. Visual Evoked Response in Children Subjected to Prenatal Maternal ...

    African Journals Online (AJOL)

    neural conduction, or arousal level. S. Afr. Med. J., 48 ... pression treatment in either development or IQ, whether ... children in brain function at an electrophysiological level, ..... Perry, N. W. and Childers, D. G. (1969): The Human Visual Evoked.

  11. Gender differences in rival characteristics that evoke jealousy in response to emotional versus sexual infidelity

    NARCIS (Netherlands)

    Buunk, Abraham (Bram); Dijkstra, Pieternel

    2004-01-01

    Previous research has shown that in men jealousy is evoked more by a rival's status-related characteristics than in women, whereas in women jealousy is evoked more by a rival's physical attractiveness than in men. The present study examined whether the occurrence of this gender difference depends

  12. Abdominal acupuncture reduces laser-evoked potentials in healthy subjects

    DEFF Research Database (Denmark)

    Pazzaglia, C.; Liguori, S.; Minciotti, I.

    2015-01-01

    Objective: Acupuncture is known to reduce clinical pain, although the exact mechanism is unknown. The aim of the current study was to investigate the effect of acupuncture on laser-evoked potential amplitudes and laser pain perception. Methods: In order to evaluate whether abdominal acupuncture...... is able to modify pain perception, 10 healthy subjects underwent a protocol in which laser-evoked potentials (LEPs) and laser pain perception were collected before the test (baseline), during abdominal acupuncture, and 15. min after needle removal. The same subjects also underwent a similar protocol...... in which, however, sham acupuncture without any needle penetration was used. Results: During real acupuncture, both N1 and N2/P2 amplitudes were reduced, as compared to baseline (p . < 0.01). The reduction lasted up to 15. min after needle removal. Furthermore, laser pain perception was reduced during...

  13. Coordination of eye and head components of movements evoked by stimulation of the paramedian pontine reticular formation

    Science.gov (United States)

    Barton, Ellen J.; Sparks, David L.

    2013-01-01

    Constant frequency microstimulation of the paramedian pontine reticular formation (PPRF) in head-restrained monkeys evokes a constant velocity eye movement. Since the PPRF receives significant projections from structures that control coordinated eye-head movements, we asked whether stimulation of the pontine reticular formation in the head-unrestrained animal generates a combined eye-head movement or only an eye movement. Microstimulation of most sites yielded a constant-velocity gaze shift executed as a coordinated eye-head movement, although eye-only movements were evoked from some sites. The eye and head contributions to the stimulation-evoked movements varied across stimulation sites and were drastically different from the lawful relationship observed for visually-guided gaze shifts. These results indicate that the microstimulation activated elements that issued movement commands to the extraocular and, for most sites, neck motoneurons. In addition, the stimulation-evoked changes in gaze were similar in the head-restrained and head-unrestrained conditions despite the assortment of eye and head contributions, suggesting that the vestibuloocular reflex (VOR) gain must be near unity during the coordinated eye-head movements evoked by stimulation of the PPRF. These findings contrast the attenuation of VOR gain associated with visually-guided gaze shifts and suggest that the vestibulo-ocular pathway processes volitional and PPRF stimulation-evoked gaze shifts differently. PMID:18458891

  14. Role of Ca+2 and other second messengers in excitatory amino acid receptor mediated neurodegeneration: clinical perspectives

    DEFF Research Database (Denmark)

    Schousboe, A; Belhage, B; Frandsen, A

    1997-01-01

    Neurodegeneration associated with neurological disorders such as epilepsy, Huntington's Chorea, Alzheimer's disease, and olivoponto cerebellar atrophy or with energy failure such as ischemia, hypoxia, and hypoglycemia proceeds subsequent to overexposure of neurons to excitatory amino acids of which...... glutamate and aspartate may be quantitatively the most important. The toxic action of glutamate and aspartate is mediated through activation of glutamate receptors of the N-methyl-D-aspartate (NMDA) and non-NMDA subtypes. Antagonists for these receptors can act as neuroprotectants both in in vitro model...

  15. Different Stimulation Frequencies Alter Synchronous Fluctuations in Motor Evoked Potential Amplitude of Intrinsic Hand Muscles—a TMS Study

    Science.gov (United States)

    Sale, Martin V.; Rogasch, Nigel C.; Nordstrom, Michael A.

    2016-01-01

    The amplitude of motor-evoked potentials (MEPs) elicited with transcranial magnetic stimulation (TMS) varies from trial-to-trial. Synchronous oscillations in cortical neuronal excitability contribute to this variability, however it is not known how different frequencies of stimulation influence MEP variability, and whether these oscillations are rhythmic or aperiodic. We stimulated the motor cortex with TMS at different regular (i.e., rhythmic) rates, and compared this with pseudo-random (aperiodic) timing. In 18 subjects, TMS was applied at three regular frequencies (0.05 Hz, 0.2 Hz, 1 Hz) and one aperiodic frequency (mean 0.2 Hz). MEPs (n = 50) were recorded from three intrinsic hand muscles of the left hand with different functional and anatomical relations. MEP amplitude correlation was highest for the functionally related muscle pair, less for the anatomically related muscle pair and least for the functionally- and anatomically-unrelated muscle pair. MEP correlations were greatest with 1 Hz, and least for stimulation at 0.05 Hz. Corticospinal neuron synchrony is higher with shorter TMS intervals. Further, corticospinal neuron synchrony is similar irrespective of whether the stimulation is periodic or aperiodic. These findings suggest TMS frequency is a crucial consideration for studies using TMS to probe correlated activity between muscle pairs. PMID:27014031

  16. Absence of both auditory evoked potentials and auditory percepts dependent on timing cues.

    Science.gov (United States)

    Starr, A; McPherson, D; Patterson, J; Don, M; Luxford, W; Shannon, R; Sininger, Y; Tonakawa, L; Waring, M

    1991-06-01

    An 11-yr-old girl had an absence of sensory components of auditory evoked potentials (brainstem, middle and long-latency) to click and tone burst stimuli that she could clearly hear. Psychoacoustic tests revealed a marked impairment of those auditory perceptions dependent on temporal cues, that is, lateralization of binaural clicks, change of binaural masked threshold with changes in signal phase, binaural beats, detection of paired monaural clicks, monaural detection of a silent gap in a sound, and monaural threshold elevation for short duration tones. In contrast, auditory functions reflecting intensity or frequency discriminations (difference limens) were only minimally impaired. Pure tone audiometry showed a moderate (50 dB) bilateral hearing loss with a disproportionate severe loss of word intelligibility. Those auditory evoked potentials that were preserved included (1) cochlear microphonics reflecting hair cell activity; (2) cortical sustained potentials reflecting processing of slowly changing signals; and (3) long-latency cognitive components (P300, processing negativity) reflecting endogenous auditory cognitive processes. Both the evoked potential and perceptual deficits are attributed to changes in temporal encoding of acoustic signals perhaps occurring at the synapse between hair cell and eighth nerve dendrites. The results from this patient are discussed in relation to previously published cases with absent auditory evoked potentials and preserved hearing.

  17. Methodologic aspects of acetylcholine-evoked relaxation of rabbit aorta

    DEFF Research Database (Denmark)

    Larsen, Kirsten Vendelbo; Nedergaard, Ove A.

    1999-01-01

    The acetylcholine-evoked relaxation of rabbit isolated thoracic aorta precontracted by phenylephrine was studied. Phenylephrine caused a steady contraction that was maintained for 6 h. In the presence of calcium disodium ethylenediaminetetraacetate (EDTA) and ascorbic acid the contraction decreased...

  18. A transgenic mouse line for molecular genetic analysis of excitatory glutamatergic neurons

    DEFF Research Database (Denmark)

    Borgius, Lotta; Restrepo, C. Ernesto; Leao, Richardson N.

    2010-01-01

    Excitatory glutamatergic neurons are part of most of the neuronal circuits in the mammalian nervous system. We have used BAC-technology to generate a BAC-Vglut2::Cre mouse line where Cre expression is driven by the vesicular glutamate transporter 2 (Vglut2) promotor. This BAC-Vglut2::Cre mouse line...... showed specific expression of Cre in Vglut2 positive cells in the spinal cord with no ectopic expression in GABAergic or glycinergic neurons. This mouse line also showed specific Cre expression in Vglut2 positive structures in the brain such as thalamus, hypothalamus, superior colliculi, inferior...... colliculi and deep cerebellar nuclei together with nuclei in the midbrain and hindbrain. Cre-mediated recombination was restricted to Cre expressing cells in the spinal cord and brain and occurred as early as E 12.5. Known Vglut2 positive neurons showed normal electrophysiological properties in the BAC...

  19. Measures of spontaneous and movement-evoked pain are associated with disability in patients with whiplash injuries.

    Science.gov (United States)

    Mankovsky-Arnold, Tsipora; Wideman, Timothy H; Larivière, Christian; Sullivan, Michael J L

    2014-09-01

    This study examined the degree to which measures of spontaneous and movement-evoked pain accounted for shared or unique variance in functional disability associated with whiplash injury. The study also addressed the role of fear of movement as a mediator or moderator of the relation between different indices of pain and functional disability. Measures of spontaneous pain, single-point movement-evoked pain, repetition-induced summation of activity-related pain (RISP), and fear of movement and disability were obtained on a sample of 142 individuals who had sustained whiplash injuries. Participants' pain ratings, provided after lifting a weighted canister, were used as the index of single-point movement-evoked pain. RISP was computed as the increase in pain reported by participants over successive lifts of 18 weighted canisters. Measures of functional disability included physical lift tolerance and self-reported disability. Hierarchical regression analyses revealed that measures of single-point movement-evoked pain and RISP accounted for significant unique variance in self-reported disability, beyond the variance accounted for by the measure of spontaneous pain. Only RISP accounted for significant unique variance in lift tolerance. The results suggest that measures of movement-evoked pain represent a disability-relevant dimension of pain that is not captured by measures of spontaneous pain. The clinical and conceptual implications of the findings are discussed. This study examined the degree to which measures of spontaneous and movement-evoked pain accounted for shared or unique variance in functional disability associated with whiplash injury. The findings suggest that approaches to the clinical evaluation of pain would benefit from the inclusion of measures of movement-evoked pain. Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.

  20. Torque decrease during submaximal evoked contractions of the quadriceps muscle is linked not only to muscle fatigue.

    Science.gov (United States)

    Matkowski, Boris; Lepers, Romuald; Martin, Alain

    2015-05-01

    The aim of this study was to analyze the neuromuscular mechanisms involved in the torque decrease induced by submaximal electromyostimulation (EMS) of the quadriceps muscle. It was hypothesized that torque decrease after EMS would reflect the fatigability of the activated motor units (MUs), but also a reduction in the number of MUs recruited as a result of changes in axonal excitability threshold. Two experiments were performed on 20 men to analyze 1) the supramaximal twitch superimposed and evoked at rest during EMS (Experiment 1, n = 9) and 2) the twitch response and torque-frequency relation of the MUs activated by EMS (Experiment 2, n = 11). Torque loss was assessed by 15 EMS-evoked contractions (50 Hz; 6 s on/6 s off), elicited at a constant intensity that evoked 20% of the maximal voluntary contraction (MVC) torque. The same stimulation intensity delivered over the muscles was used to induce the torque-frequency relation and the single electrical pulse evoked after each EMS contraction (Experiment 2). In Experiment 1, supramaximal twitch was induced by femoral nerve stimulation. Torque decreased by ~60% during EMS-evoked contractions and by only ~18% during MVCs. This was accompanied by a rightward shift of the torque-frequency relation of MUs activated and an increase of the ratio between the superimposed and posttetanic maximal twitch evoked during EMS contraction. These findings suggest that the torque decrease observed during submaximal EMS-evoked contractions involved muscular mechanisms but also a reduction in the number of MUs recruited due to changes in axonal excitability. Copyright © 2015 the American Physiological Society.

  1. The mast cell degranulator compound 48/80 directly activates neurons.

    Directory of Open Access Journals (Sweden)

    Michael Schemann

    Full Text Available BACKGROUND: Compound 48/80 is widely used in animal and tissue models as a "selective" mast cell activator. With this study we demonstrate that compound 48/80 also directly activates enteric neurons and visceral afferents. METHODOLOGY/PRINCIPAL FINDINGS: We used in vivo recordings from extrinsic intestinal afferents together with Ca(++ imaging from primary cultures of DRG and nodose neurons. Enteric neuronal activation was examined by Ca(++ and voltage sensitive dye imaging in isolated gut preparations and primary cultures of enteric neurons. Intraluminal application of compound 48/80 evoked marked afferent firing which desensitized on subsequent administration. In egg albumen-sensitized animals, intraluminal antigen evoked a similar pattern of afferent activation which also desensitized on subsequent exposure to antigen. In cross-desensitization experiments prior administration of compound 48/80 failed to influence the mast cell mediated response. Application of 1 and 10 µg/ml compound 48/80 evoked spike discharge and Ca(++ transients in enteric neurons. The same nerve activating effect was observed in primary cultures of DRG and nodose ganglion cells. Enteric neuron cultures were devoid of mast cells confirmed by negative staining for c-kit or toluidine blue. In addition, in cultured enteric neurons the excitatory action of compound 48/80 was preserved in the presence of histamine H(1 and H(2 antagonists. The mast cell stabilizer cromolyn attenuated compound 48/80 and nicotine evoked Ca(++ transients in mast cell-free enteric neuron cultures. CONCLUSIONS/SIGNIFICANCE: The results showed direct excitatory action of compound 48/80 on enteric neurons and visceral afferents. Therefore, functional changes measured in tissue or animal models may involve a mast cell independent effect of compound 48/80 and cromolyn.

  2. Serial recording of median nerve stimulated subcortical somatosensory evoked potentials (SEPs) in developing brain death.

    Science.gov (United States)

    Buchner, H; Ferbert, A; Hacke, W

    1988-01-01

    Subcortical somatosensory evoked potentials (SEPs) to median nerve stimulation were recorded serially in 35 patients during the evolution towards brain death and in brain death. Neuropathological alterations of the central nervous system down to the C1/C2 spinal cord segment in brain death are well known. SEP components supposed to be generated above this level should be lost in brain death, while components generated below should not be altered. Erb's point, scalp and neck potentials were recorded at C3/4, or over the spinous process C7, using an Fz reference. In 10 patients additional montages, including spinous process C2-Fz, a non-cephalic reference (Fz-contralateral shoulder) and a posterior to anterior neck montage (spinous process C7-jugulum) were used. The cephalic referenced N9 and N11 peaks remained unchanged until brain death. N9 and N11 decreased in parallel in amplitude and increased in latency after systemic effects like hypoxia or hypothermia occurred. The cephalic referenced 'N14' decreased in amplitude and increased in latency after the clinical brain death syndrome was observed, while N13 in the posterior to anterior neck montage remained unchanged. The alteration of 'N14' went parallel to the decrease of the P14 amplitude. The subcortical SEPs in the cephalic referenced lead are supposed to be a peak composed by a horizontally orientated dorsal horn generated N13 and a rostrally orientated P14 arising at the level of the foramen magnum. The deterioration of the non-cephalic referenced P14 and of its cephalic referenced reflection 'N14' seems to provide an additional objective criterion for the diagnosis of brain death.

  3. Evoked responses to sinusoidally modulated sound in unanaesthetized dogs

    NARCIS (Netherlands)

    Tielen, A.M.; Kamp, A.; Lopes da Silva, F.H.; Reneau, J.P.; Storm van Leeuwen, W.

    1. 1. Responses evoked by sinusoidally amplitude-modulated sound in unanaesthetized dogs have been recorded from inferior colliculus and from auditory cortex structures by means of chronically indwelling stainless steel wire electrodes. 2. 2. Harmonic analysis of the average responses demonstrated

  4. Anabolic steroids alter the physiological activity of aggression circuits in the lateral anterior hypothalamus.

    Science.gov (United States)

    Morrison, T R; Sikes, R W; Melloni, R H

    2016-02-19

    Syrian hamsters exposed to anabolic/androgenic steroids (AAS) during adolescence consistently show increased aggressive behavior across studies. Although the behavioral and anatomical profiles of AAS-induced alterations have been well characterized, there is a lack of data describing physiological changes that accompany these alterations. For instance, behavioral pharmacology and neuroanatomical studies show that AAS-induced changes in the vasopressin (AVP) neural system within the latero-anterior hypothalamus (LAH) interact with the serotonin (5HT) and dopamine (DA) systems to modulate aggression. To characterize the electrophysiological profile of the AAS aggression circuit, we recorded LAH neurons in adolescent male hamsters in vivo and microiontophoretically applied agonists and antagonists of aggressive behavior. The interspike interval (ISI) of neurons from AAS-treated animals correlated positively with aggressive behaviors, and adolescent AAS exposure altered parameters of activity in regular firing neurons while also changing the proportion of neuron types (i.e., bursting, regular, irregular). AAS-treated animals had more responsive neurons that were excited by AVP application, while cells from control animals showed the opposite effect and were predominantly inhibited by AVP. Both DA D2 antagonists and 5HT increased the firing frequency of AVP-responsive cells from AAS animals and dual application of AVP and D2 antagonists doubled the excitatory effect of AVP or D2 antagonist administration alone. These data suggest that multiple DA circuits in the LAH modulate AAS-induced aggressive responding. More broadly, these data show that multiple neurochemical interactions at the neurophysiological level are altered by adolescent AAS exposure. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. Multi-channel motor evoked potential monitoring during anterior cervical discectomy and fusion

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    Dong-Gun Kim

    Full Text Available Objectives: Anterior cervical discectomy and fusion (ACDF surgery is the most common surgical procedure for the cervical spine with low complication rate. Despite the potential prognostic benefit, intraoperative neurophysiological monitoring (IONM, a method for detecting impending neurological compromise, is not routinely used in ACDF surgery. The present study aimed to identify the potential benefits of monitoring multi-channel motor evoked potentials (MEPs during ACDF surgery. Methods: We retrospectively reviewed 200 consecutive patients who received IONM with multi-channel MEPs and somatosensory evoked potentials (SSEPs. On average, 9.2 muscles per patient were evaluated under MEP monitoring. Results: The rate of MEP change during surgery in the multi-level ACDF group was significantly higher than the single-level group. Two patients from the single-level ACDF group (1.7% and four patients from the multi-level ACDF group (4.9% experienced post-operative motor deficits. Multi-channel MEPs monitoring during single and multi-level ACDF surgery demonstrated higher sensitivity, specificity, positive predictive and negative predictive value than SSEP monitoring. Conclusions: Multi-channel MEP monitoring might be beneficial for the detection of segmental injury as well as long tract injury during single- and multi-level ACDF surgery. Significance: This is first large scale study to identify the usefulness of multi-channel MEPs in monitoring ACDF surgery. Keywords: Disc disease, Somatosensory evoked potentials, Intraoperative neurophysiological monitoring, Motor evoked potentials, Anterior cervical discectomy and fusion

  6. Sensory-specific associations stored in the lateral amygdala allow for selective alteration of fear memories.

    Science.gov (United States)

    Díaz-Mataix, Lorenzo; Debiec, Jacek; LeDoux, Joseph E; Doyère, Valérie

    2011-06-29

    Consolidated long-term fear memories become labile and can be disrupted after being reactivated by the presentation of the unconditioned stimulus (US). Whether this is due to an alteration of the conditioned stimulus (CS) representation in the lateral amygdala (LA) is not known. Here, we show in rats that fear memory reactivation through presentation of the aversive US, like CS presentation, triggers a process which, when disrupted, results in a selective depotentiation of CS-evoked neural responses in the LA in correlation with a selective suppression of CS-elicited fear memory. Thus, an aversive US triggers the reconsolidation of its associated predictor representation in LA. This new finding suggests that sensory-specific associations are stored in the lateral amygdala, allowing for their selective alteration by either element of the association.

  7. Guanfacine potentiates the activation of prefrontal cortex evoked by warning signals.

    Science.gov (United States)

    Clerkin, Suzanne M; Schulz, Kurt P; Halperin, Jeffrey M; Newcorn, Jeffrey H; Ivanov, Iliyan; Tang, Cheuk Y; Fan, Jin

    2009-08-15

    Warning signals evoke an alert state of readiness that prepares for a rapid response by priming a thalamo-frontal-striatal network that includes the dorsolateral prefrontal cortex (DLPFC). Animal models indicate that noradrenergic input is essential for this stimulus-driven activation of DLPFC, but the precise mechanisms involved have not been determined. We tested the role that postsynaptic alpha(2A) adrenoceptors play in the activation of DLPFC evoked by warning cues using a placebo-controlled challenge with the alpha(2A) agonist guanfacine. Sixteen healthy young adults were scanned twice with event-related functional magnetic resonance imaging (fMRI), while performing a simple cued reaction time (RT) task following administration of a single dose of oral guanfacine (1 mg) and placebo in counterbalanced order. The RT task temporally segregates the neural effects of warning cues and motor responses and minimizes mnemonic demands. Warning cues produced a marked reduction in RT accompanied by significant activation in a distributed thalamo-frontal-striatal network, including bilateral DLPFC. Guanfacine selectively increased the cue-evoked activation of the left DLPFC and right anterior cerebellum, although this increase was not accompanied by further reductions in RT. The effects of guanfacine on DLPFC activation were specifically associated with the warning cue and were not seen for visual- or target-related activation. Guanfacine produced marked increases in the cue-evoked activation of DLPFC that correspond to the well-described actions of postsynaptic alpha(2) adrenoceptor stimulation. The current procedures provide an opportunity to test postsynaptic alpha(2A) adrenoceptor function in the prefrontal cortex in the pathophysiology of several psychiatric disorders.

  8. [Effects of sevoflurane and propofol on evoked potentials during neurosurgical anesthesia].

    Science.gov (United States)

    Nakagawa, Itsuo; Hidaka, Syozo; Okada, Hironori; Kubo, Takashi; Okamura, Kenta; Kato, Takahiro

    2006-06-01

    The effect of anesthetics on somatosensory evoked potential (SEP) and auditory brain stem response (ABR) has been a subject of intense reseach over the last two decades. In fact, volatile anesthetics have been repeatedly shown to decrease cortical amplitude in a dose-dependent fashion but the information regarding the effect of propofol is incomplete. The purpose of this study was to compare the effects of sevoflurane and propofol on evoked potentials during comparable depth of anesthesia guided by bispectral index (BIS). Forty four patients scheduled for neurosurgery were studied. Anesthesia was maintained with intravenous propofol using target controlled infusion (TCI). We measured the change of amplitude and latency of SEP(N20-P25), ABR (V wave) and visual evoked potential (VEP: P100) at three sets of sevoflurane (0%, 1%, 2%) or propofol concentrations (effect site concentration of 1.5, 2.0, 3.0 microug x ml(-1)). BIS monitor was used to measure relative depth of hypnosis. With increasing concentrations of sevoflurane (0, 1% and 2%), SEP showed dose-related reduction in its amplitude, ABR produced less marked changes and VEP showed a significant reduction at 1%. VEP at the propofol concentration of 3.0 microg x ml(-1) was decreased significantly compared with the amplitude at 1.5 microg x ml(-1) concentration. No significant change was observed with SEP and ABR during the change of propofol dosages. BIS values were almost the same with each anesthetics. VEP was most strongly affected with anesthetics, and ABR showed less marked influence of sevoflurane and propofol. Propofol based TIVA technique would induce less change in evoked potentials than sevoflurane.

  9. Methylenetetrahydrofolate reductase deficiency alters levels of glutamate and γ-aminobutyric acid in brain tissue

    Directory of Open Access Journals (Sweden)

    N.M. Jadavji

    2015-06-01

    Full Text Available Methylenetetrahydrofolate reductase (MTHFR is an enzyme key regulator in folate metabolism. Deficiencies in MTHFR result in increased levels of homocysteine, which leads to reduced levels of S-adenosylmethionine (SAM. In the brain, SAM donates methyl groups to catechol-O-methyltransferase (COMT, which is involved in neurotransmitter analysis. Using the MTHFR-deficient mouse model the purpose of this study was to investigate levels of monoamine neurotransmitters and amino acid levels in brain tissue. MTHFR deficiency affected levels of both glutamate and γ-aminobutyric acid in within the cerebellum and hippocampus. Mthfr−/− mice had reduced levels of glutamate in the amygdala and γ-aminobutyric acid in the thalamus. The excitatory mechanisms of homocysteine through activation of the N-methyl-d-aspartate receptor in brain tissue might alter levels of glutamate and γ-aminobutyric acid.

  10. Mechanism of Transport Modulation by an Extracellular Loop in an Archaeal Excitatory Amino Acid Transporter (EAAT) Homolog*

    Science.gov (United States)

    Mulligan, Christopher; Mindell, Joseph A.

    2013-01-01

    Secondary transporters in the excitatory amino acid transporter family terminate glutamatergic synaptic transmission by catalyzing Na+-dependent removal of glutamate from the synaptic cleft. Recent structural studies of the aspartate-specific archaeal homolog, GltPh, suggest that transport is achieved by a rigid body, piston-like movement of the transport domain, which houses the substrate-binding site, between the extracellular and cytoplasmic sides of the membrane. This transport domain is connected to an immobile scaffold by three loops, one of which, the 3–4 loop (3L4), undergoes substrate-sensitive conformational change. Proteolytic cleavage of the 3L4 was found to abolish transport activity indicating an essential function for this loop in the transport mechanism. Here, we demonstrate that despite the presence of fully cleaved 3L4, GltPh is still able to sample conformations relevant for transport. Optimized reconstitution conditions reveal that fully cleaved GltPh retains some transport activity. Analysis of the kinetics and temperature dependence of transport accompanied by direct measurements of substrate binding reveal that this decreased transport activity is not due to alteration of the substrate binding characteristics but is caused by the significantly reduced turnover rate. By measuring solute counterflow activity and cross-link formation rates, we demonstrate that cleaving 3L4 severely and specifically compromises one or more steps contributing to the movement of the substrate-loaded transport domain between the outward- and inward-facing conformational states, sparing the equivalent step(s) during the movement of the empty transport domain. These results reveal a hitherto unknown role for the 3L4 in modulating an essential step in the transport process. PMID:24155238

  11. Theta Burst Stimulation of the Cerebellum Modifies the TMS-Evoked N100 Potential, a Marker of GABA Inhibition.

    Directory of Open Access Journals (Sweden)

    Allanah Harrington

    Full Text Available Theta burst stimulation (TBS of the cerebellum, a potential therapy for neurological disease, can modulate corticospinal excitability via the dentato-thalamo-cortical pathway, but it is uncertain whether its effects are mediated via inhibitory or facilitatory networks. The aim of this study was to investigate the effects of 30Hz cerebellar TBS on the N100 waveform of the TMS-evoked potential (TEP, a marker of intracortical GABAB-mediated inhibition. 16 healthy participants (aged 18-30 years; 13 right handed and 3 left handed received 30Hz intermittent TBS (iTBS, continuous TBS (cTBS or sham stimulation over the right cerebellum, in three separate sessions. The first 8 participants received TBS at a stimulus intensity of 80% of active motor threshold (AMT, while the remainder received 90% of AMT. Motor evoked potentials (MEP and TEP were recorded before and after each treatment, by stimulating the first dorsal interosseus area of the left motor cortex. Analysis of the 13 right handed participants showed that iTBS at 90% of AMT increased the N100 amplitude compared to sham and cTBS, without significantly altering MEP amplitude. cTBS at 80% of active motor threshold decreased the N100 amplitude and cTBS overall reduced resting MEP amplitude. The study demonstrates effects of 30Hz cerebellar TBS on inhibitory cortical networks that may be useful for treatment of neurological conditions associated with dysfunctional intracortical inhibition.

  12. Norepinephrine induces pathway-specific long-lasting potentiation and depression in the hippocampal dentate gyrus.

    Science.gov (United States)

    Dahl, D; Sarvey, J M

    1989-01-01

    The study presented here indicates that norepinephrine (NE) selectively induces long-lasting modifications of synaptically mediated responses in the dentate gyrus of the rat hippocampal slice. A low concentration of NE (1.0 microM; in the presence of 50 microM phentolamine, an alpha-adrenergic antagonist) or a 1.0 microM concentration of the specific beta-adrenergic agonist isoproterenol induced long-lasting pathway-specific alterations of granule cell electrophysiological responses. Excitatory postsynaptic potentials and population spikes evoked by stimulation of the medial perforant pathway (PP) were potentiated for more than 45 min. In contrast, responses to lateral PP stimulation were depressed for the same period. Both potentiation and depression were blocked by the beta-adrenergic antagonist propranolol (1.0 microM). These results indicate that NE can act differentially on projections to the dentate gyrus arising in the entorhinal cortex. Such selective persistent modifications of cortical circuits may be involved in processes in the mammalian brain underlying attention, learning, and memory. PMID:2734319

  13. Mapping pathological phenotypes in a mouse model of CDKL5 disorder.

    Directory of Open Access Journals (Sweden)

    Elena Amendola

    Full Text Available Mutations in cyclin-dependent kinase-like 5 (CDKL5 cause early-onset epileptic encephalopathy, a neurodevelopmental disorder with similarities to Rett Syndrome. Here we describe the physiological, molecular, and behavioral phenotyping of a Cdkl5 conditional knockout mouse model of CDKL5 disorder. Behavioral analysis of constitutive Cdkl5 knockout mice revealed key features of the human disorder, including limb clasping, hypoactivity, and abnormal eye tracking. Anatomical, physiological, and molecular analysis of the knockout uncovered potential pathological substrates of the disorder, including reduced dendritic arborization of cortical neurons, abnormal electroencephalograph (EEG responses to convulsant treatment, decreased visual evoked responses (VEPs, and alterations in the Akt/rpS6 signaling pathway. Selective knockout of Cdkl5 in excitatory and inhibitory forebrain neurons allowed us to map the behavioral features of the disorder to separable cell-types. These findings identify physiological and molecular deficits in specific forebrain neuron populations as possible pathological substrates in CDKL5 disorder.

  14. Mapping pathological phenotypes in a mouse model of CDKL5 disorder.

    Science.gov (United States)

    Amendola, Elena; Zhan, Yang; Mattucci, Camilla; Castroflorio, Enrico; Calcagno, Eleonora; Fuchs, Claudia; Lonetti, Giuseppina; Silingardi, Davide; Vyssotski, Alexei L; Farley, Dominika; Ciani, Elisabetta; Pizzorusso, Tommaso; Giustetto, Maurizio; Gross, Cornelius T

    2014-01-01

    Mutations in cyclin-dependent kinase-like 5 (CDKL5) cause early-onset epileptic encephalopathy, a neurodevelopmental disorder with similarities to Rett Syndrome. Here we describe the physiological, molecular, and behavioral phenotyping of a Cdkl5 conditional knockout mouse model of CDKL5 disorder. Behavioral analysis of constitutive Cdkl5 knockout mice revealed key features of the human disorder, including limb clasping, hypoactivity, and abnormal eye tracking. Anatomical, physiological, and molecular analysis of the knockout uncovered potential pathological substrates of the disorder, including reduced dendritic arborization of cortical neurons, abnormal electroencephalograph (EEG) responses to convulsant treatment, decreased visual evoked responses (VEPs), and alterations in the Akt/rpS6 signaling pathway. Selective knockout of Cdkl5 in excitatory and inhibitory forebrain neurons allowed us to map the behavioral features of the disorder to separable cell-types. These findings identify physiological and molecular deficits in specific forebrain neuron populations as possible pathological substrates in CDKL5 disorder.

  15. Cortical modulation of short-latency TMS-evoked potentials

    Directory of Open Access Journals (Sweden)

    Domenica eVeniero

    2013-01-01

    Full Text Available Transcranial magnetic stimulation - electroencephalogram (TMS-EEG co-registration offers the opportunity to test reactivity of brain areas across distinct conditions through TMS-evoked potentials (TEPs. Several TEPs have been described, their functional meaning being largely unknown. In particular, short-latency potentials peaking at 5 (P5 and 8 (N8 ms after the TMS pulse have been recently described, but because of their huge amplitude, the problem of whether their origin is cortical or not has been opened. To gain information about these components, we employed a protocol that modulates primary motor cortex excitability (MI through an exclusively cortical phenomena: low frequency stimulation of premotor area (PMC. TMS was applied simultaneously with EEG recording from 70 electrodes. Amplitude of TEPs evoked by 200 single-pulses TMS delivered over MI at 110% of resting motor threshold was measured before and after applying 900 TMS conditioning stimuli to left premotor cortex with 1 Hz repetition rate. Single subject analyses showed reduction in TEPs amplitude after PMC conditioning in a sample of participants and increase in TEPs amplitude in two subjects. No effects were found on corticospinal excitability as recorded by motor evoked potentials (MEPs. Furthermore, correlation analysis showed an inverse relation between the effects of the conditioning protocol on P5-N8 complex amplitude and MEPs amplitude. Because the effects of the used protocol have been ascribed to a cortical interaction between premotor area and MI, we suggest that despite the sign of P5-N8 amplitude modulation is not consistent across participant, this modulation could indicate, at least in part, their cortical origin. We conclude that with an accurate experimental procedure early-latency components can be used to evaluate the reactivity of the stimulated cortex.

  16. The roles of superficial amygdala and auditory cortex in music-evoked fear and joy.

    Science.gov (United States)

    Koelsch, Stefan; Skouras, Stavros; Fritz, Thomas; Herrera, Perfecto; Bonhage, Corinna; Küssner, Mats B; Jacobs, Arthur M

    2013-11-01

    This study investigates neural correlates of music-evoked fear and joy with fMRI. Studies on neural correlates of music-evoked fear are scant, and there are only a few studies on neural correlates of joy in general. Eighteen individuals listened to excerpts of fear-evoking, joy-evoking, as well as neutral music and rated their own emotional state in terms of valence, arousal, fear, and joy. Results show that BOLD signal intensity increased during joy, and decreased during fear (compared to the neutral condition) in bilateral auditory cortex (AC) and bilateral superficial amygdala (SF). In the right primary somatosensory cortex (area 3b) BOLD signals increased during exposure to fear-evoking music. While emotion-specific activity in AC increased with increasing duration of each trial, SF responded phasically in the beginning of the stimulus, and then SF activity declined. Psychophysiological Interaction (PPI) analysis revealed extensive emotion-specific functional connectivity of AC with insula, cingulate cortex, as well as with visual, and parietal attentional structures. These findings show that the auditory cortex functions as a central hub of an affective-attentional network that is more extensive than previously believed. PPI analyses also showed functional connectivity of SF with AC during the joy condition, taken to reflect that SF is sensitive to social signals with positive valence. During fear music, SF showed functional connectivity with visual cortex and area 7 of the superior parietal lobule, taken to reflect increased visual alertness and an involuntary shift of attention during the perception of auditory signals of danger. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. High-frequency stimulation-induced peptide release synchronizes arcuate kisspeptin neurons and excites GnRH neurons

    Science.gov (United States)

    Qiu, Jian; Nestor, Casey C; Zhang, Chunguang; Padilla, Stephanie L; Palmiter, Richard D

    2016-01-01

    Kisspeptin (Kiss1) and neurokinin B (NKB) neurocircuits are essential for pubertal development and fertility. Kisspeptin neurons in the hypothalamic arcuate nucleus (Kiss1ARH) co-express Kiss1, NKB, dynorphin and glutamate and are postulated to provide an episodic, excitatory drive to gonadotropin-releasing hormone 1 (GnRH) neurons, the synaptic mechanisms of which are unknown. We characterized the cellular basis for synchronized Kiss1ARH neuronal activity using optogenetics, whole-cell electrophysiology, molecular pharmacology and single cell RT-PCR in mice. High-frequency photostimulation of Kiss1ARH neurons evoked local release of excitatory (NKB) and inhibitory (dynorphin) neuropeptides, which were found to synchronize the Kiss1ARH neuronal firing. The light-evoked synchronous activity caused robust excitation of GnRH neurons by a synaptic mechanism that also involved glutamatergic input to preoptic Kiss1 neurons from Kiss1ARH neurons. We propose that Kiss1ARH neurons play a dual role of driving episodic secretion of GnRH through the differential release of peptide and amino acid neurotransmitters to coordinate reproductive function. DOI: http://dx.doi.org/10.7554/eLife.16246.001 PMID:27549338

  18. The effect of digital signage on shoppers’ behavior: the role of the evoked experience

    OpenAIRE

    Dennis, Charles; Brakus, J. Joško; Gupta, Suraksha; Alamanos, Eleftherios

    2014-01-01

    This paper investigates the role of digital signage as experience provider in retail spaces. The findings of a survey-based field experiment demonstrate that digital signage content high on sensory cues evokes affective experience and strengthens customers' experiential processing route. In contrast, digital signage messages high on “features and benefits” information evoke intellectual experience and strengthen customers' deliberative processing route. The affective experience is more strong...

  19. Perceptual learning of acoustic noise generates memory-evoked potentials.

    Science.gov (United States)

    Andrillon, Thomas; Kouider, Sid; Agus, Trevor; Pressnitzer, Daniel

    2015-11-02

    Experience continuously imprints on the brain at all stages of life. The traces it leaves behind can produce perceptual learning [1], which drives adaptive behavior to previously encountered stimuli. Recently, it has been shown that even random noise, a type of sound devoid of acoustic structure, can trigger fast and robust perceptual learning after repeated exposure [2]. Here, by combining psychophysics, electroencephalography (EEG), and modeling, we show that the perceptual learning of noise is associated with evoked potentials, without any salient physical discontinuity or obvious acoustic landmark in the sound. Rather, the potentials appeared whenever a memory trace was observed behaviorally. Such memory-evoked potentials were characterized by early latencies and auditory topographies, consistent with a sensory origin. Furthermore, they were generated even on conditions of diverted attention. The EEG waveforms could be modeled as standard evoked responses to auditory events (N1-P2) [3], triggered by idiosyncratic perceptual features acquired through learning. Thus, we argue that the learning of noise is accompanied by the rapid formation of sharp neural selectivity to arbitrary and complex acoustic patterns, within sensory regions. Such a mechanism bridges the gap between the short-term and longer-term plasticity observed in the learning of noise [2, 4-6]. It could also be key to the processing of natural sounds within auditory cortices [7], suggesting that the neural code for sound source identification will be shaped by experience as well as by acoustics. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Alterity In/Of Happiness: Reflecting on the radical possibilities of unruly bodies

    Directory of Open Access Journals (Sweden)

    E. Chandler

    2013-11-01

    Full Text Available This paper examines how fat and disabled subjects may be taught to appear as happy through biopedagogies in order to manage shame and disgust evoked by their unruly, non-conforming bodies. We begin by articulating what we mean by “biopedagogies”. We then unpack how the requirement to be happy feeds directly into a neoliberal agenda, which demands we must take care of ourselves both economically and emotionally in order to be considered good citizens. We explore how, in the midst of the requirement to be happy while living in bodies not recognised as inhabitable, we create and find moments of alterity in/of happiness. Through analysing art by disabled and fat activists and artists, we examine how disabled and fat people find happiness in difference, rather than in spite of it while at the same time, hanging on to rage and dull pain within this alterity of happiness.

  1. A Parallel World for the World Bank: A Case Study of Urgent: Evoke, An Educational Alternate Reality Game

    Directory of Open Access Journals (Sweden)

    David I. Waddington

    2013-01-01

    Full Text Available In 2010, the World Bank launched Urgent: Evoke, an alternate reality game. Conceived in response to the demands of African universities, the game was designed to promote the World Bank Institute’s vision of positive global change through social innovation, and made substantial use of Web 2.0 tools such as blogs, personal profiles, and social networks. This article offers a case study of Urgent: Evoke, divided into four sections: first, the potential to use video games as citizenship education tools is discussed; second, the unique game genre (alternate reality games into which Evoke falls is explained and some possible uses of this genre in higher education are examined; third, the functioning of the Evoke game world is explained; and fourth, the results of the Evoke educational project are assessed. The case study concludes with some commentary on Evoke’s ideological message, which those less sympathetic to capitalism may view as problematic.

  2. Repeated injections of piracetam improve spatial learning and increase the stimulation of inositol phospholipid hydrolysis by excitatory amino acids in aged rats

    NARCIS (Netherlands)

    Canonico, P. L.; Aronica, E.; Aleppo, G.; Casabona, G.; Copani, A.; Favit, A.; Nicoletti, F.; Scapagnini, U.

    1991-01-01

    Repeated injections of piracetam (400 mg/kg, i.p. once a day for 15 days) to 16-month old rats led to an improved performance on an 8-arm radial maze, used as a test for spatial learning. This effect was accompanied by a greater ability of excitatory amino acids (ibotenate and glutamate) to

  3. Dynamic properties of sensory stimulation evoked responses in mouse cerebellar granule cell layer and molecular layer.

    Science.gov (United States)

    Bing, Yan-Hua; Zhang, Guang-Jian; Sun, Lei; Chu, Chun-Ping; Qiu, De-Lai

    2015-01-12

    Sensory information coming from climbing fiber and mossy fiber-granule cell pathways, generates motor-related outputs according to internal rules of integration and computation in the cerebellar cortex. However, the dynamic properties of sensory information processing in mouse cerebellar cortex are less understood. Here, we studied the dynamic properties of sensory stimulation-evoked responses in the cerebellar granule cell layer (GCL) and molecular layer (ML) by electrophysiological recordings method. Our data showed that air-puff stimulation (5-10 ms in duration) of the ipsilateral whisker pad evoked single-peak responses in the GCL and ML; whereas a duration of stimulation ≥30 ms in GCL and ≥60 ms in ML, evoked double-peak responses that corresponded with stimulation-on and -off responses via mossy fiber pathway. The highest frequency of stimulation train for evoking GCL responses was 33 Hz. In contrast, the highest frequency of stimulation train for evoking ML responses was 4 Hz. These results indicate that the cerebellar granule cells transfer the high-fidelity sensory information from mossy fibers, which is cut-off by molecular layer interneurons (MLIs). Our results suggest that the MLIs network acts as a low-pass filter during the processing of high-frequency sensory information. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. An Excitatory Neural Assembly Encodes Short-Term Memory in the Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Yonglu Tian

    2018-02-01

    Full Text Available Short-term memory (STM is crucial for animals to hold information for a small period of time. Persistent or recurrent neural activity, together with neural oscillations, is known to encode the STM at the cellular level. However, the coding mechanisms at the microcircuitry level remain a mystery. Here, we performed two-photon imaging on behaving mice to monitor the activity of neuronal microcircuitry. We discovered a neuronal subpopulation in the medial prefrontal cortex (mPFC that exhibited emergent properties in a context-dependent manner underlying a STM-like behavior paradigm. These neuronal subpopulations exclusively comprise excitatory neurons and mainly represent a group of neurons with stronger functional connections. Microcircuitry plasticity was maintained for minutes and was absent in an animal model of Alzheimer’s disease (AD. Thus, these results point to a functional coding mechanism that relies on the emergent behavior of a functionally defined neuronal assembly to encode STM.

  5. A Cyfip2-Dependent Excitatory Interneuron Pathway Establishes the Innate Startle Threshold.

    Science.gov (United States)

    Marsden, Kurt C; Jain, Roshan A; Wolman, Marc A; Echeverry, Fabio A; Nelson, Jessica C; Hayer, Katharina E; Miltenberg, Ben; Pereda, Alberto E; Granato, Michael

    2018-04-17

    Sensory experiences dynamically modify whether animals respond to a given stimulus, but it is unclear how innate behavioral thresholds are established. Here, we identify molecular and circuit-level mechanisms underlying the innate threshold of the zebrafish startle response. From a forward genetic screen, we isolated five mutant lines with reduced innate startle thresholds. Using whole-genome sequencing, we identify the causative mutation for one line to be in the fragile X mental retardation protein (FMRP)-interacting protein cyfip2. We show that cyfip2 acts independently of FMRP and that reactivation of cyfip2 restores the baseline threshold after phenotype onset. Finally, we show that cyfip2 regulates the innate startle threshold by reducing neural activity in a small group of excitatory hindbrain interneurons. Thus, we identify a selective set of genes critical to establishing an innate behavioral threshold and uncover a circuit-level role for cyfip2 in this process. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  6. A comparison of auditory evoked potentials to acoustic beats and to binaural beats

    OpenAIRE

    Pratt, H; Starr, A; Michalewski, HJ; Dimitrijevic, A; Bleich, N; Mittelman, N

    2010-01-01

    The purpose of this study was to compare cortical brain responses evoked by amplitude modulated acoustic beats of 3 and 6 Hz in tones of 250 and 1000 Hz with those evoked by their binaural beats counterparts in unmodulated tones to indicate whether the cortical processes involved differ. Event-related potentials (ERPs) were recorded to 3- and 6-Hz acoustic and binaural beats in 2000 ms duration 250 and 1000 Hz tones presented with approximately 1 s intervals. Latency, amplitude and source cur...

  7. Transmitter-controlled properties of α-motoneurones causing long-lasting motor discharge to brief excitatory inputs

    DEFF Research Database (Denmark)

    Hounsgaard, J.; Hultborn, H.; Kiehn, O.

    1986-01-01

    Brief sensory inputs to intact conscious subjects commonly trigger complex long-lasting motor responses, in which higher cerebral mechanisms, or even voluntary action, may be integrative parts. However, long-lasting motor discharge following brief afferent stimulation is also observed in reduced ...... flipflops, which are set at one of two levels by short excitatory or inhibitory inputs. However, when the whole motoneuronal pool is considered, many different levels can be maintained by recruitment of new units.......Brief sensory inputs to intact conscious subjects commonly trigger complex long-lasting motor responses, in which higher cerebral mechanisms, or even voluntary action, may be integrative parts. However, long-lasting motor discharge following brief afferent stimulation is also observed in reduced...

  8. Effects of monomethylarsonic and monomethylarsonous acid on evoked synaptic potentials in hippocampal slices of adult and young rats

    International Nuclear Information System (INIS)

    Krueger, Katharina; Straub, Heidrun; Hirner, Alfred V.; Hippler, Joerg; Binding, Norbert; Musshoff, Ulrich

    2009-01-01

    Arsenite and its metabolites, dimethylarsinic or dimethylarsinous acid, have previously been shown to disturb synaptic transmission in hippocampal slices of rats (Krueger, K., Gruner, J., Madeja, M., Hartmann, L.M., Hirner, A.V., Binding, N., Muβhoff, U., 2006a. Blockade and enhancement of glutamate receptor responses in Xenopus oocytes by methylated arsenicals. Arch. Toxicol. 80, 492-501, Krueger, K., Straub, H., Binding, N., Muβhoff, U., 2006b. Effects of arsenite on long-term potentiation in hippocampal slices from adult and young rats. Toxicol. Lett. 165, 167-173, Krueger, K., Repges, H., Hippler, J., Hartmann, L.M., Hirner, A.V., Straub, H., Binding, N., Muβhoff, U., 2007. Effects of dimethylarsinic and dimethylarsinous acid on evoked synaptic potentials in hippocampal slices of young and adult rats. Toxicol. Appl. Pharmacol. 225, 40-46). The present experiments investigate, whether the important arsenic metabolites monomethylarsonic acid (MMA V ) and monomethylarsonous acid (MMA III ) also influence the synaptic functions of the hippocampus. In hippocampal slices of young (14-21 days-old) and adult (2-4 months-old) rats, evoked synaptic field potentials from the Schaffer collateral-CA1 synapse were measured under control conditions and during and after 30 and 60 min of application of the arsenic compounds. MMA V had no effect on the synapse functions neither in slices of adult nor in those from young rats. However, MMA III strongly influenced the synaptic transmission: it totally depressed the amplitudes of fEPSPs at concentrations of 50 μmol/l (adult rats) and 25 μmol/l (young rats) and LTP amplitudes at concentrations of 25 μmol/l (adult rats) and 10 μmol/l (young rats), respectively. In contrast, application of 1 μmol/l MMA III led to an enhancement of the LTP amplitude in young rats, which is interpretable by an enhancing effect on NMDA receptors and a lack of the blocking effect on AMPA receptors at this concentration (Krueger, K., Gruner, J

  9. Occipital lobe lesions result in a displacement of magnetoencephalography visual evoked field dipoles.

    Science.gov (United States)

    Pang, Elizabeth W; Chu, Bill H W; Otsubo, Hiroshi

    2014-10-01

    The pattern-reversal visual evoked potential measured electrically from scalp electrodes is known to be decreased, or absent, in patients with occipital lobe lesions. We questioned whether the measurement and source analysis of the neuromagnetic visual evoked field (VEF) might offer additional information regarding visual cortex relative to the occipital lesion. We retrospectively examined 12 children (6-18 years) with occipital lesions on MRI, who underwent magnetoencephalography and ophthalmology as part of their presurgical assessment. Binocular half-field pattern-reversal VEFs were obtained in a 151-channel whole-head magnetoencephalography. Data were averaged and dipole source analyses were performed for each half-field stimulation. A significant lateral shift (P occipital lesions. Magnetoencephalography may be useful as a screening test of visual function in young patients. We discuss potential explanations for this lateral shift and emphasize the utility of adding the magnetoencephalography pattern-reversal visual evoked field protocol to the neurologic work-up.

  10. Excitatory strength of expressive faces: effects of happy and fear expressions and context on the extinction of a conditioned fear response.

    Science.gov (United States)

    Lanzetta, J T; Orr, S P

    1986-01-01

    In a recent study, Orr and Lanzetta (1984) showed that the excitatory properties of fear facial expressions previously described (Lanzetta & Orr, 1981; Orr & Lanzetta, 1980) do not depend on associative mechanisms; even in the absence of reinforcement, fear faces intensify the emotional reaction to a previously conditioned stimulus and disrupt extinction of an acquired fear response. In conjunction with the findings on acquisition, the failure to obtain extinction suggests that fear faces have some of the functional properties of "prepared" (fear-relevant) stimuli. In the present study we compared the magnitude of conditioned fear responses to happy and fear faces when a potent danger signal, the shock electrodes, are attached or unattached. If fear faces are functionally analogous to prepared stimuli, then, even in the absence of veridical support for an expectation of shock, they should retain excitatory strength, whereas happy faces should not. The results are consistent with this view of fear expressions. In the absence of reinforcement, and with shock electrodes removed, conditioned fear responses and basal levels of arousal were of greater magnitude for the fear-face condition than for the happy-face condition.

  11. Evoked traveling alpha waves predict visual-semantic categorization-speed

    Science.gov (United States)

    Fellinger, Robert; Gruber, Walter; Zauner, Andrea; Freunberger, Roman; Klimesch, Wolfgang

    2012-01-01

    In the present study we have tested the hypothesis that evoked traveling alpha waves are behaviorally significant. The results of a visual-semantic categorization task show that three early ERP components including the P1–N1 complex had a dominant frequency characteristic in the alpha range and behaved like traveling waves do. They exhibited a traveling direction from midline occipital to right lateral parietal sites. Phase analyses revealed that this traveling behavior of ERP components could be explained by phase-delays in the alpha but not theta and beta frequency range. Most importantly, we found that the speed of the traveling alpha wave was significantly and negatively correlated with reaction time indicating that slow traveling speed was associated with fast picture-categorization. We conclude that evoked alpha oscillations are functionally associated with early access to visual-semantic information and generate – or at least modulate – the early waveforms of the visual ERP. PMID:22100769

  12. Synaptic Homeostasis and Allostasis in the Dentate Gyrus Caused by Inflammatory and Neuropathic Pain Conditions

    Directory of Open Access Journals (Sweden)

    Rui-Rui Wang

    2018-01-01

    Full Text Available It has been generally accepted that pain can cause imbalance between excitation and inhibition (homeostasis at the synaptic level. However, it remains poorly understood how this imbalance (allostasis develops in the CNS under different pain conditions. Here, we analyzed the changes in both excitatory and inhibitory synaptic transmission and modulation of the dentate gyrus (DG under two pain conditions with different etiology and duration. First, it was revealed that the functions of the input-output (I/O curves for evoked excitatory postsynaptic currents (eEPSCs following the perforant path (PP stimulation were gained under both acute inflammatory and chronic neuropathic pain conditions relative to the controls. However, the functions of I/O curves for the PP-evoked inhibitory postsynaptic currents (eIPSCs differed between the two conditions, namely it was greatly gained under inflammatory condition, but was reduced under neuropathic condition in reverse. Second, both the frequency and amplitude of miniature IPSCs (mIPSCs were increased under inflammatory condition, however a decrease in frequency of mIPSCs was observed under neuropathic condition. Finally, the spike discharge of the DG granule cells in response to current injection was significantly increased by neuropathic pain condition, however, no different change was found between inflammatory pain condition and the control. These results provide another line of evidence showing homeostatic and allostatic modulation of excitatory synaptic transmission by inhibitory controls under different pathological pain conditions, hence implicating use of different therapeutic approaches to maintain the homeostasis between excitation and inhibition while treating different conditions of pathological pain.

  13. Analysis of Spontaneous and Nerve-Evoked Calcium Transients in Intact Extraocular Muscles in Vitro

    Science.gov (United States)

    Feng, Cheng-Yuan; Hennig, Grant W.; Corrigan, Robert D.; Smith, Terence K.; von Bartheld, Christopher S.

    2012-01-01

    Extraocular muscles (EOMs) have unique calcium handling properties, yet little is known about the dynamics of calcium events underlying ultrafast and tonic contractions in myofibers of intact EOMs. Superior oblique EOMs of juvenile chickens were dissected with their nerve attached, maintained in oxygenated Krebs buffer, and loaded with fluo-4. Spontaneous and nerve stimulation-evoked calcium transients were recorded and, following calcium imaging, some EOMs were double-labeled with rhodamine-conjugated alpha-bungarotoxin (rhBTX) to identify EOM myofiber types. EOMs showed two main types of spontaneous calcium transients, one slow type (calcium waves with 1/2max duration of 2–12 s, velocity of 25–50 μm/s) and two fast “flash-like” types (Type 1, 30–90 ms; Type 2, 90–150 ms 1/2max duration). Single pulse nerve stimulation evoked fast calcium transients identical to the fast (Type 1) calcium transients. Calcium waves were accompanied by a local myofiber contraction that followed the calcium transient wavefront. The magnitude of calcium-wave induced myofiber contraction far exceeded those of movement induced by nerve stimulation and associated fast calcium transients. Tetrodotoxin eliminated nerve-evoked transients, but not spontaneous transients. Alpha-bungarotoxin eliminated both spontaneous and nerve-evoked fast calcium transients, but not calcium waves, and caffeine increased wave activity. Calcium waves were observed in myofibers lacking spontaneous or evoked fast transients, suggestive of multiply-innervated myofibers, and this was confirmed by double-labeling with rhBTX. We propose that the abundant spontaneous calcium transients and calcium waves with localized contractions that do not depend on innervation may contribute to intrinsic generation of tonic functions of EOMs. PMID:22579493

  14. Thermoreceptive innervation of human glabrous and hairy skin: a contact heat evoked potential analysis.

    Science.gov (United States)

    Granovsky, Yelena; Matre, Dagfinn; Sokolik, Alexander; Lorenz, Jürgen; Casey, Kenneth L

    2005-06-01

    The human palm has a lower heat detection threshold and a higher heat pain threshold than hairy skin. Neurophysiological studies of monkeys suggest that glabrous skin has fewer low threshold heat nociceptors (AMH type 2) than hairy skin. Accordingly, we used a temperature-controlled contact heat evoked potential (CHEP) stimulator to excite selectively heat receptors with C fibers or Adelta-innervated AMH type 2 receptors in humans. On the dorsal hand, 51 degrees C stimulation produced painful pinprick sensations and 41 degrees C stimuli evoked warmth. On the glabrous thenar, 41 degrees C stimulation produced mild warmth and 51 degrees C evoked strong but painless heat sensations. We used CHEP responses to estimate the conduction velocities (CV) of peripheral fibers mediating these sensations. On hairy skin, 41 degrees C stimuli evoked an ultra-late potential (mean, SD; N wave latency: 455 (118) ms) mediated by C fibers (CV by regression analysis: 1.28 m/s, N=15) whereas 51 degrees C stimuli evoked a late potential (N latency: 267 (33) ms) mediated by Adelta afferents (CV by within-subject analysis: 12.9 m/s, N=6). In contrast, thenar responses to 41 and 51 degrees C were mediated by C fibers (average N wave latencies 485 (100) and 433 (73) ms, respectively; CVs 0.95-1.35 m/s by regression analysis, N=15; average CV=1.7 (0.41) m/s calculated from distal glabrous and proximal hairy skin stimulation, N=6). The exploratory range of the human and monkey palm is enhanced by the abundance of low threshold, C-innervated heat receptors and the paucity of low threshold AMH type 2 heat nociceptors.

  15. Abnormal cortical synaptic transmission in CaV2.1 knockin mice with the S218L missense mutation which causes a severe familial hemiplegic migraine syndrome in humans

    Science.gov (United States)

    Vecchia, Dania; Tottene, Angelita; van den Maagdenberg, Arn M.J.M.; Pietrobon, Daniela

    2015-01-01

    Familial hemiplegic migraine type 1 (FHM1) is caused by gain-of-function mutations in CaV2.1 (P/Q-type) Ca2+ channels. Knockin (KI) mice carrying the FHM1 R192Q missense mutation show enhanced cortical excitatory synaptic transmission at pyramidal cell synapses but unaltered cortical inhibitory neurotransmission at fast-spiking interneuron synapses. Enhanced cortical glutamate release was shown to cause the facilitation of cortical spreading depression (CSD) in R192Q KI mice. It, however, remains unknown how other FHM1 mutations affect cortical synaptic transmission. Here, we studied neurotransmission in cortical neurons in microculture from KI mice carrying the S218L mutation, which causes a severe FHM syndrome in humans and an allele-dosage dependent facilitation of experimental CSD in KI mice, which is larger than that caused by the R192Q mutation. We show gain-of-function of excitatory neurotransmission, due to increased action-potential evoked Ca2+ influx and increased probability of glutamate release at pyramidal cell synapses, but unaltered inhibitory neurotransmission at multipolar interneuron synapses in S218L KI mice. In contrast with the larger gain-of-function of neuronal CaV2.1 current in homozygous than heterozygous S218L KI mice, the gain-of-function of evoked glutamate release, the paired-pulse ratio and the Ca2+ dependence of the excitatory postsynaptic current were similar in homozygous and heterozygous S218L KI mice, suggesting compensatory changes in the homozygous mice. Furthermore, we reveal a unique feature of S218L KI cortical synapses which is the presence of a fraction of mutant CaV2.1 channels being open at resting potential. Our data suggest that, while the gain-of-function of evoked glutamate release may explain the facilitation of CSD in heterozygous S218L KI mice, the further facilitation of CSD in homozygous S218L KI mice is due to other CaV2.1-dependent mechanisms, that likely include Ca2+ influx at voltages sub-threshold for action

  16. A new structural class of subtype-selective inhibitor of cloned excitatory amino acid transporter, EAAT2

    DEFF Research Database (Denmark)

    Bräuner-Osborne, Hans; Hermit, M B; Nielsen, B

    2000-01-01

    We have studied the pharmacological effects of (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) and the enantiomers of (RS)-2-amino-3-(3-hydroxy-1,2, 5-thiadiazol-4-yl)propionic acid (TDPA) on cloned human excitatory amino acid transporter subtypes 1, 2 and 3 (EAAT1......-3) expressed in Cos-7 cells. Whereas AMPA and (R)-TDPA were both inactive as inhibitors of [3H]-(R)-aspartic acid uptake on all three EAAT subtypes, (S)-TDPA was shown to selectively inhibit uptake by EAAT2 with a potency equal to that of the endogenous ligand (S)-glutamic acid. (S)-TDPA thus represents a new...

  17. Impact of weak excitatory synapses on chaotic transients in a diffusively coupled Morris-Lecar neuronal network

    Energy Technology Data Exchange (ETDEWEB)

    Lafranceschina, Jacopo, E-mail: jlafranceschina@alaska.edu; Wackerbauer, Renate, E-mail: rawackerbauer@alaska.edu [Department of Physics, University of Alaska, Fairbanks, Alaska 99775-5920 (United States)

    2015-01-15

    Spatiotemporal chaos collapses to either a rest state or a propagating pulse solution in a ring network of diffusively coupled, excitable Morris-Lecar neurons. Weak excitatory synapses can increase the Lyapunov exponent, expedite the collapse, and promote the collapse to the rest state rather than the pulse state. A single traveling pulse solution may no longer be asymptotic for certain combinations of network topology and (weak) coupling strengths, and initiate spatiotemporal chaos. Multiple pulses can cause chaos initiation due to diffusive and synaptic pulse-pulse interaction. In the presence of chaos initiation, intermittent spatiotemporal chaos exists until typically a collapse to the rest state.

  18. Impact of weak excitatory synapses on chaotic transients in a diffusively coupled Morris-Lecar neuronal network

    International Nuclear Information System (INIS)

    Lafranceschina, Jacopo; Wackerbauer, Renate

    2015-01-01

    Spatiotemporal chaos collapses to either a rest state or a propagating pulse solution in a ring network of diffusively coupled, excitable Morris-Lecar neurons. Weak excitatory synapses can increase the Lyapunov exponent, expedite the collapse, and promote the collapse to the rest state rather than the pulse state. A single traveling pulse solution may no longer be asymptotic for certain combinations of network topology and (weak) coupling strengths, and initiate spatiotemporal chaos. Multiple pulses can cause chaos initiation due to diffusive and synaptic pulse-pulse interaction. In the presence of chaos initiation, intermittent spatiotemporal chaos exists until typically a collapse to the rest state

  19. The 170ms Response to Faces as Measured by MEG (M170 Is Consistently Altered in Congenital Prosopagnosia.

    Directory of Open Access Journals (Sweden)

    Andreas Lueschow

    Full Text Available Modularity of face processing is still a controversial issue. Congenital prosopagnosia (cPA, a selective and lifelong impairment in familiar face recognition without evidence of an acquired cerebral lesion, offers a unique opportunity to support this fundamental hypothesis. However, in spite of the pronounced behavioural impairment, identification of a functionally relevant neural alteration in congenital prosopagnosia by electrophysiogical methods has not been achieved so far. Here we show that persons with congenital prosopagnosia can be distinguished as a group from unimpaired persons using magnetoencephalography. Early face-selective MEG-responses in the range of 140 to 200ms (the M170 showed prolonged latency and decreased amplitude whereas responses to another category (houses were indistinguishable between subjects with congenital prosopagnosia and unimpaired controls. Latency and amplitude of face-selective EEG responses (the N170 which were simultaneously recorded were statistically indistinguishable between subjects with cPA and healthy controls which resolves heterogeneous and partly conflicting results from existing studies. The complementary analysis of categorical differences (evoked activity to faces minus evoked activity to houses revealed that the early part of the 170ms response to faces is altered in subjects with cPA. This finding can be adequately explained in a common framework of holistic and part-based face processing. Whereas a significant brain-behaviour correlation of face recognition performance and the size of the M170 amplitude is found in controls a corresponding correlation is not seen in subjects with cPA. This indicates functional relevance of the alteration found for the 170ms response to faces in cPA and pinpoints the impairment of face processing to early perceptual stages.

  20. Direct electrical stimulation of human cortex evokes high gamma activity that predicts conscious somatosensory perception

    Science.gov (United States)

    Muller, Leah; Rolston, John D.; Fox, Neal P.; Knowlton, Robert; Rao, Vikram R.; Chang, Edward F.

    2018-04-01

    Objective. Direct electrical stimulation (DES) is a clinical gold standard for human brain mapping and readily evokes conscious percepts, yet the neurophysiological changes underlying these percepts are not well understood. Approach. To determine the neural correlates of DES, we stimulated the somatosensory cortex of ten human participants at frequency-amplitude combinations that both elicited and failed to elicit conscious percepts, meanwhile recording neural activity directly surrounding the stimulation site. We then compared the neural activity of perceived trials to that of non-perceived trials. Main results. We found that stimulation evokes distributed high gamma activity, which correlates with conscious perception better than stimulation parameters themselves. Significance. Our findings suggest that high gamma activity is a reliable biomarker for perception evoked by both natural and electrical stimuli.

  1. Evoked responses of the superior olive to amplitude-modulated signals.

    Science.gov (United States)

    Andreeva, N G; Lang, T T

    1977-01-01

    Evoked potentials of some auditory centers of Rhinolophidae bats to amplitude-modulated signals were studied. A synchronization response was found in the cochlear nuclei (with respect to the fast component of the response) and in the superior olivary complex (with respect to both fast and slow components of the response) within the range of frequency modulation from 50 to 2000 Hz. In the inferior colliculus a synchronized response was recorded at modulation frequencies below 150 Hz, but in the medial geniculate bodies no such response was found. Evoked responses of the superior olivary complex were investigated in detail. The lowest frequencies of synchronization were recorded within the carrier frequency range of 15-30 and 80-86 kHz. The amplitude of the synchronized response is a function of the frequency and coefficient of modulation and also of the angle of stimulus presentation.

  2. Role played by acid-sensitive ion channels in evoking the exercise pressor reflex.

    Science.gov (United States)

    Hayes, Shawn G; McCord, Jennifer L; Rainier, Jon; Liu, Zhuqing; Kaufman, Marc P

    2008-10-01

    The exercise pressor reflex arises from contracting skeletal muscle and is believed to play a role in evoking the cardiovascular responses to static exercise, effects that include increases in arterial pressure and heart rate. This reflex is believed to be evoked by the metabolic and mechanical stimulation of thin fiber muscle afferents. Lactic acid is known to be an important metabolic stimulus evoking the reflex. Until recently, the only antagonist for acid-sensitive ion channels (ASICs), the receptors to lactic acid, was amiloride, a substance that is also a potent antagonist for both epithelial sodium channels as well as voltage-gated sodium channels. Recently, a second compound, A-317567, has been shown to be an effective and selective antagonist to ASICs in vitro. Consequently, we measured the pressor responses to the static contraction of the triceps surae muscles in decerebrate cats before and after a popliteal arterial injection of A-317567 (10 mM solution; 0.5 ml). We found that this ASIC antagonist significantly attenuated by half (Pacid injection into the popliteal artery. In contrast, A-317567 had no effect on the pressor responses to tendon stretch, a pure mechanical stimulus, and to a popliteal arterial injection of capsaicin, which stimulated transient receptor potential vanilloid type 1 channels. We conclude that ASICs on thin fiber muscle afferents play a substantial role in evoking the metabolic component of the exercise pressor reflex.

  3. Intrasexual competition at work : Sex differences in the jealousy-evoking effect of rival characteristics in work settings

    NARCIS (Netherlands)

    Buunk, Abraham P.; 't Goor, Joel Aan; Solano, Alejandro C.

    Sex differences in jealousy-evoking rival characteristics in the relationship with a supervisor at work were examined in a community sample of 188 individuals from Argentina. Among men, the rivals' social dominance and communal attributes evoked the most jealousy, followed by physical dominance.

  4. Different stimulation frequencies alter synchronous fluctuations in motor evoked potential amplitude of intrinsic hand muscles – a TMS study.

    Directory of Open Access Journals (Sweden)

    Martin Victor Sale

    2016-03-01

    Full Text Available The amplitude of motor-evoked potentials (MEPs elicited with transcranial magnetic stimulation (TMS varies from trial-to-trial. Synchronous oscillations in cortical neuronal excitability contribute to this variability, however it is not known how different frequencies of stimulation influence MEP variability, and whether these oscillations are rhythmic or aperiodic. We stimulated the motor cortex with TMS at different regular (i.e., rhythmic rates, and compared this with pseudo-random (aperiodic timing. In 18 subjects, TMS was applied at three regular frequencies (0.05 Hz, 0.2 Hz, 1 Hz and one aperiodic frequency (mean 0.2 Hz. MEPs (n = 50 were recorded from three intrinsic hand muscles of the left hand with different functional and anatomical relations. MEP amplitude correlation was highest for the functionally related muscle pair, less for the anatomically related muscle pair and least for the functionally- and anatomically-unrelated muscle pair. MEP correlations were greatest with 1 Hz, and least for stimulation at 0.05 Hz. Corticospinal neuron synchrony is higher with shorter TMS intervals. Further, corticospinal neuron synchrony is similar irrespective of whether the stimulation is periodic or aperiodic. These findings suggest TMS frequency is a crucial consideration for studies using TMS to probe correlated activity between muscle pairs.

  5. The role of Magnetic Resonance Imaging and Visual Evoked ...

    African Journals Online (AJOL)

    Introduction: To report our experience in management of patients with optic neuritis. The effects of brain magnetic resonance imaging and visual evoked potential on management were investigated. Methods: This is a four years clinical trial that included patients presenting with first attack of optic neuritis older than 16 years ...

  6. Visual impairment in FOXG1-mutated individuals and mice.

    Science.gov (United States)

    Boggio, E M; Pancrazi, L; Gennaro, M; Lo Rizzo, C; Mari, F; Meloni, I; Ariani, F; Panighini, A; Novelli, E; Biagioni, M; Strettoi, E; Hayek, J; Rufa, A; Pizzorusso, T; Renieri, A; Costa, M

    2016-06-02

    The Forkead Box G1 (FOXG1 in humans, Foxg1 in mice) gene encodes for a DNA-binding transcription factor, essential for the development of the telencephalon in mammalian forebrain. Mutations in FOXG1 have been reported to be involved in the onset of Rett Syndrome, for which sequence alterations of MECP2 and CDKL5 are known. While visual alterations are not classical hallmarks of Rett syndrome, an increasing body of evidence shows visual impairment in patients and in MeCP2 and CDKL5 animal models. Herein we focused on the functional role of FOXG1 in the visual system of animal models (Foxg1(+/Cre) mice) and of a cohort of subjects carrying FOXG1 mutations or deletions. Visual physiology of Foxg1(+/Cre) mice was assessed by visually evoked potentials, which revealed a significant reduction in response amplitude and visual acuity with respect to wild-type littermates. Morphological investigation showed abnormalities in the organization of excitatory/inhibitory circuits in the visual cortex. No alterations were observed in retinal structure. By examining a cohort of FOXG1-mutated individuals with a panel of neuro-ophthalmological assessments, we found that all of them exhibited visual alterations compatible with high-level visual dysfunctions. In conclusion our data show that Foxg1 haploinsufficiency results in an impairment of mouse and human visual cortical function. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Prior Expectations Evoke Stimulus Templates in the Primary Visual Cortex

    NARCIS (Netherlands)

    Kok, P.; Failing, F.M.; de Lange, F.P.

    2014-01-01

    Exposure to rhythmic stimulation results in facilitated responses to events that appear in-phase with the rhythm and modulation of anticipatory and target-evoked brain activity, presumably reflecting "exogenous," unintentional temporal expectations. However, the extent to which this effect is

  8. Multimodal evoked potentials follow up in multiple sclerosis patients under fingolimod therapy

    DEFF Research Database (Denmark)

    Iodice, R; Carotenuto, A; Dubbioso, R

    2016-01-01

    related to EDSS at baseline (t=-1), while MEP and total EP sum score were related to EDSS at all time points. CONCLUSION: Fingolimod is able to improve visual and somatosensory evoked potential in RR-MS patients even if clinical disability scale remains stable. VEP and SEP could give eloquent information...... patients examined 12months prior to initiation of fingolimod (t=-1), at treatment initiation (t=0) and 1year later (t=+1) were compared. Each EP (VEP, MEP, SEP) and EP sum score, a global evoked potential score as the sum score of the each EP score was evaluated and correlated with Expanded Disability...

  9. Serotonin, dopamine and noradrenaline adjust actions of myelinated afferents via modulation of presynaptic inhibition in the mouse spinal cord.

    Directory of Open Access Journals (Sweden)

    David L García-Ramírez

    Full Text Available Gain control of primary afferent neurotransmission at their intraspinal terminals occurs by several mechanisms including primary afferent depolarization (PAD. PAD produces presynaptic inhibition via a reduction in transmitter release. While it is known that descending monoaminergic pathways complexly regulate sensory processing, the extent these actions include modulation of afferent-evoked PAD remains uncertain. We investigated the effects of serotonin (5HT, dopamine (DA and noradrenaline (NA on afferent transmission and PAD. Responses were evoked by stimulation of myelinated hindlimb cutaneous and muscle afferents in the isolated neonatal mouse spinal cord. Monosynaptic responses were examined in the deep dorsal horn either as population excitatory synaptic responses (recorded as extracellular field potentials; EFPs or intracellular excitatory postsynaptic currents (EPSCs. The magnitude of PAD generated intraspinally was estimated from electrotonically back-propagating dorsal root potentials (DRPs recorded on lumbar dorsal roots. 5HT depressed the DRP by 76%. Monosynaptic actions were similarly depressed by 5HT (EFPs 54%; EPSCs 75% but with a slower time course. This suggests that depression of monosynaptic EFPs and DRPs occurs by independent mechanisms. DA and NA had similar depressant actions on DRPs but weaker effects on EFPs. IC50 values for DRP depression were 0.6, 0.8 and 1.0 µM for 5HT, DA and NA, respectively. Depression of DRPs by monoamines was nearly-identical in both muscle and cutaneous afferent-evoked responses, supporting a global modulation of the multimodal afferents stimulated. 5HT, DA and NA produced no change in the compound antidromic potentials evoked by intraspinal microstimulation indicating that depression of the DRP is unrelated to direct changes in the excitability of intraspinal afferent fibers, but due to metabotropic receptor activation. In summary, both myelinated afferent-evoked DRPs and monosynaptic

  10. Effect of mechanical tactile noise on amplitude of visual evoked potentials: multisensory stochastic resonance.

    Science.gov (United States)

    Méndez-Balbuena, Ignacio; Huidobro, Nayeli; Silva, Mayte; Flores, Amira; Trenado, Carlos; Quintanar, Luis; Arias-Carrión, Oscar; Kristeva, Rumyana; Manjarrez, Elias

    2015-10-01

    The present investigation documents the electrophysiological occurrence of multisensory stochastic resonance in the human visual pathway elicited by tactile noise. We define multisensory stochastic resonance of brain evoked potentials as the phenomenon in which an intermediate level of input noise of one sensory modality enhances the brain evoked response of another sensory modality. Here we examined this phenomenon in visual evoked potentials (VEPs) modulated by the addition of tactile noise. Specifically, we examined whether a particular level of mechanical Gaussian noise applied to the index finger can improve the amplitude of the VEP. We compared the amplitude of the positive P100 VEP component between zero noise (ZN), optimal noise (ON), and high mechanical noise (HN). The data disclosed an inverted U-like graph for all the subjects, thus demonstrating the occurrence of a multisensory stochastic resonance in the P100 VEP. Copyright © 2015 the American Physiological Society.

  11. Probing for improved potency and in vivo bioavailability of excitatory amino acid transporter subtype 1 inhibitors UCPH-101 and UCPH-102: Design, synthesis and pharmacological evaluation of substituted 7-biphenyl analogs

    DEFF Research Database (Denmark)

    Erichsen, Mette Norman; Hansen, J; Artacho Ruiz, Jose

    2014-01-01

    Uptake of the major excitatory neurotransmitter in the CNS, (S)-glutamate, is mediated by a family of excitatory amino acid transporters (EAAT). Previously we have explored the structure-activity relationship (SAR) of a series of EAAT1 selective inhibitors, leading to the development of the potent...... were designed, synthesized and characterized pharmacologically at EAAT1-3 in a [(3)H]-D-aspartate uptake assay. Most notably, the potent EAAT1 inhibition displayed of UCPH-101 and UCPH-102 was retained in analog 1d in which the napht-1-yl group in the 7-position of UCPH-102 has been replaced by an o...

  12. High fructose corn syrup induces metabolic dysregulation and altered dopamine signaling in the absence of obesity.

    Science.gov (United States)

    Meyers, Allison M; Mourra, Devry; Beeler, Jeff A

    2017-01-01

    The contribution of high fructose corn syrup (HFCS) to metabolic disorder and obesity, independent of high fat, energy-rich diets, is controversial. While high-fat diets are widely accepted as a rodent model of diet-induced obesity (DIO) and metabolic disorder, the value of HFCS alone as a rodent model of DIO is unclear. Impaired dopamine function is associated with obesity and high fat diet, but the effect of HFCS on the dopamine system has not been investigated. The objective of this study was to test the effect of HFCS on weight gain, glucose regulation, and evoked dopamine release using fast-scan cyclic voltammetry. Mice (C57BL/6) received either water or 10% HFCS solution in combination with ad libitum chow for 15 weeks. HFCS consumption with chow diet did not induce weight gain compared to water, chow-only controls but did induce glucose dysregulation and reduced evoked dopamine release in the dorsolateral striatum. These data show that HFCS can contribute to metabolic disorder and altered dopamine function independent of weight gain and high-fat diets.

  13. High fructose corn syrup induces metabolic dysregulation and altered dopamine signaling in the absence of obesity.

    Directory of Open Access Journals (Sweden)

    Allison M Meyers

    Full Text Available The contribution of high fructose corn syrup (HFCS to metabolic disorder and obesity, independent of high fat, energy-rich diets, is controversial. While high-fat diets are widely accepted as a rodent model of diet-induced obesity (DIO and metabolic disorder, the value of HFCS alone as a rodent model of DIO is unclear. Impaired dopamine function is associated with obesity and high fat diet, but the effect of HFCS on the dopamine system has not been investigated. The objective of this study was to test the effect of HFCS on weight gain, glucose regulation, and evoked dopamine release using fast-scan cyclic voltammetry. Mice (C57BL/6 received either water or 10% HFCS solution in combination with ad libitum chow for 15 weeks. HFCS consumption with chow diet did not induce weight gain compared to water, chow-only controls but did induce glucose dysregulation and reduced evoked dopamine release in the dorsolateral striatum. These data show that HFCS can contribute to metabolic disorder and altered dopamine function independent of weight gain and high-fat diets.

  14. DC-Evoked Modulation of Excitability of Myelinated Nerve Fibers and Their Terminal Branches; Differences in Sustained Effects of DC.

    Science.gov (United States)

    Kaczmarek, Dominik; Jankowska, Elzbieta

    2018-03-15

    Direct current (DC) evokes long-lasting changes in neuronal networks both presynaptically and postsynaptically and different mechanisms were proposed to be involved in them. Different mechanisms were also suggested to account for the different dynamics of presynaptic DC actions on myelinated nerve fibers stimulated before they entered the spinal gray matter and on their terminal branches. The aim of the present study was to examine whether these different dynamics might be related to differences in the involvement of K + channels. To this end, we compared effects of the K + channel blocker 4-amino-pyridine (4-AP) on DC-evoked changes in the excitability of afferent fibers stimulated within the dorsal columns (epidurally) and within their projection areas in the dorsal horn and motor nuclei (intraspinally). 4-AP was applied systemically in deeply anesthetized rats. DC-evoked increases in the excitability of epidurally stimulated afferent nerve fibers, and increases in field potentials evoked by these fibers, were not affected by 4-AP. In contrast, sustained decreases rather than increases in the excitability of intraspinally stimulated terminal nerve branches were evoked by local application of DC in conjunction with 4-AP. The study leads to the conclusion that 4-AP-sensitive K + channels contribute to the sustained DC-evoked post-polarization increases in the excitability at the level of terminal branches of nerve fibers but not of the nodes of Ranvier nor within the juxta-paranodal regions where other mechanisms would be involved in inducing the sustained DC-evoked changes. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. Torque and mechanomyogram relationships during electrically-evoked isometric quadriceps contractions in persons with spinal cord injury.

    Science.gov (United States)

    Ibitoye, Morufu Olusola; Hamzaid, Nur Azah; Hasnan, Nazirah; Abdul Wahab, Ahmad Khairi; Islam, Md Anamul; Kean, Victor S P; Davis, Glen M

    2016-08-01

    The interaction between muscle contractions and joint loading produces torques necessary for movements during activities of daily living. However, during neuromuscular electrical stimulation (NMES)-evoked contractions in persons with spinal cord injury (SCI), a simple and reliable proxy of torque at the muscle level has been minimally investigated. Thus, the purpose of this study was to investigate the relationships between muscle mechanomyographic (MMG) characteristics and NMES-evoked isometric quadriceps torques in persons with motor complete SCI. Six SCI participants with lesion levels below C4 [(mean (SD) age, 39.2 (7.9) year; stature, 1.71 (0.05) m; and body mass, 69.3 (12.9) kg)] performed randomly ordered NMES-evoked isometric leg muscle contractions at 30°, 60° and 90° knee flexion angles on an isokinetic dynamometer. MMG signals were detected by an accelerometer-based vibromyographic sensor placed over the belly of rectus femoris muscle. The relationship between MMG root mean square (MMG-RMS) and NMES-evoked torque revealed a very high association (R(2)=0.91 at 30°; R(2)=0.98 at 60°; and R(2)=0.97 at 90° knee angles; Ptorque, between 0.65 and 0.79 for MMG-RMS, and from 0.67 to 0.73 for MMG-PTP. Their standard error of measurements (SEM) ranged between 10.1% and 31.6% (of mean values) for torque, MMG-RMS and MMG-PTP. The MMG peak frequency (MMG-PF) of 30Hz approximated the stimulation frequency, indicating NMES-evoked motor unit firing rate. The results demonstrated knee angle differences in the MMG-RMS versus NMES-isometric torque relationship, but a similar torque related pattern for MMG-PF. These findings suggested that MMG was well associated with torque production, reliably tracking the motor unit recruitment pattern during NMES-evoked muscle contractions. The strong positive relationship between MMG signal and NMES-evoked torque production suggested that the MMG might be deployed as a direct proxy for muscle torque or fatigue measurement during

  16. Intermediate Latency-Evoked Potentials of Multimodal Cortical Vestibular Areas: Galvanic Stimulation

    Directory of Open Access Journals (Sweden)

    Stefan Kammermeier

    2017-11-01

    Full Text Available IntroductionHuman multimodal vestibular cortical regions are bilaterally anterior insulae and posterior opercula, where characteristic vestibular-related cortical potentials were previously reported under acoustic otolith stimulation. Galvanic vestibular stimulation likely influences semicircular canals preferentially. Galvanic stimulation was compared to previously established data under acoustic stimulation.Methods14 healthy right-handed subjects, who were also included in the previous acoustic potential study, showed normal acoustic and galvanic vestibular-evoked myogenic potentials. They received 2,000 galvanic binaural bipolar stimuli for each side during EEG recording.ResultsVestibular cortical potentials were found in all 14 subjects and in the pooled data of all subjects (“grand average” bilaterally. Anterior insula and posterior operculum were activated exclusively under galvanic stimulation at 25, 35, 50, and 80 ms; frontal regions at 30 and 45 ms. Potentials at 70 ms in frontal regions and at 110 ms at all of the involved regions could also be recorded; these events were also found using acoustic stimulation in our previous study.ConclusionGalvanic semicircular canal stimulation evokes specific potentials in addition to those also found with acoustic otolith stimulation in identically located regions of the vestibular cortex. Vestibular cortical regions activate differently by galvanic and acoustic input at the peripheral sensory level.SignificanceDifferential effects in vestibular cortical-evoked potentials may see clinical use in specific vertigo disorders.

  17. Automatic classification of visual evoked potentials based on wavelet decomposition

    Science.gov (United States)

    Stasiakiewicz, Paweł; Dobrowolski, Andrzej P.; Tomczykiewicz, Kazimierz

    2017-04-01

    Diagnosis of part of the visual system, that is responsible for conducting compound action potential, is generally based on visual evoked potentials generated as a result of stimulation of the eye by external light source. The condition of patient's visual path is assessed by set of parameters that describe the time domain characteristic extremes called waves. The decision process is compound therefore diagnosis significantly depends on experience of a doctor. The authors developed a procedure - based on wavelet decomposition and linear discriminant analysis - that ensures automatic classification of visual evoked potentials. The algorithm enables to assign individual case to normal or pathological class. The proposed classifier has a 96,4% sensitivity at 10,4% probability of false alarm in a group of 220 cases and area under curve ROC equals to 0,96 which, from the medical point of view, is a very good result.

  18. Neurophysiological mechanisms of bradykinin-evoked mucosal chloride secretion in guinea pig small intestine.

    Science.gov (United States)

    Qu, Mei-Hua; Ji, Wan-Sheng; Zhao, Ting-Kun; Fang, Chun-Yan; Mao, Shu-Mei; Gao, Zhi-Qin

    2016-02-15

    To investigate the mechanism for bradykinin (BK) to stimulate intestinal secretomotor neurons and intestinal chloride secretion. Muscle-stripped guinea pig ileal preparations were mounted in Ussing flux chambers for the recording of short-circuit current (Isc). Basal Isc and Isc stimulated by BK when preincubated with the BK receptors antagonist and other chemicals were recorded using the Ussing chamber system. Prostaglandin E2 (PGE2) production in the intestine was determined by enzyme immunologic assay (EIA). Application of BK or B2 receptor (B2R) agonist significantly increased the baseline Isc compared to the control. B2R antagonist, tetrodotoxin and scopolamine (blockade of muscarinic receptors) significantly suppressed the increase in Isc evoked by BK. The BK-evoked Isc was suppressed by cyclooxygenase (COX)-1 or COX-2 specific inhibitor as well as nonselective COX inhibitors. Preincubation of submucosa/mucosa preparations with BK for 10 min significantly increased PGE2 production and this was abolished by the COX-1 and COX-2 inhibitors. The BK-evoked Isc was suppressed by nonselective EP receptors and EP4 receptor antagonists, but selective EP1 receptor antagonist did not have a significant effect on the BK-evoked Isc. Inhibitors of PLC, PKC, calmodulin or CaMKII failed to suppress BK-induced PGE2 production. The results suggest that BK stimulates neurogenic chloride secretion in the guinea pig ileum by activating B2R, through COX increasing PGE2 production. The post-receptor transduction cascade includes activation of PLC, PKC, CaMK, IP3 and MAPK.

  19. Is the auditory evoked P2 response a biomarker of learning?

    Directory of Open Access Journals (Sweden)

    Kelly eTremblay

    2014-02-01

    Full Text Available Even though auditory training exercises for humans have been shown to improve certain perceptual skills of individuals with and without hearing loss, there is a lack of knowledge pertaining to which aspects of training are responsible for the perceptual gains, and which aspects of perception are changed. To better define how auditory training impacts brain and behavior, electroencephalography and magnetoencephalography have been used to determine the time course and coincidence of cortical modulations associated with different types of training. Here we focus on P1-N1-P2 auditory evoked responses (AEP, as there are consistent reports of gains in P2 amplitude following various types of auditory training experiences; including music and speech-sound training. The purpose of this experiment was to determine if the auditory evoked P2 response is a biomarker of learning. To do this, we taught native English speakers to identify a new pre-voiced temporal cue that is not used phonemically in the English language so that coinciding changes in evoked neural activity could be characterized. To differentiate possible effects of repeated stimulus exposure and a button-pushing task from learning itself, we examined modulations in brain activity in a group of participants who learned to identify the pre-voicing contrast and compared it to participants, matched in time, and stimulus exposure, that did not. The main finding was that the amplitude of the P2 auditory evoked response increased across repeated EEG sessions for all groups, regardless of any change in perceptual performance. What’s more, these effects were retained for months. Changes in P2 amplitude were attributed to changes in neural activity associated with the acquisition process and not the learned outcome itself. A further finding was the expression of a late negativity (LN wave 600-900 ms post-stimulus onset, post-training, exclusively for the group that learned to identify the pre

  20. A comparison of myogenic motor evoked responses to electrical and magnetic transcranial stimulation during nitrous oxide/opioid anesthesia

    NARCIS (Netherlands)

    Ubags, L. H.; Kalkman, C. J.; Been, H. D.; Koelman, J. H.; Ongerboer de Visser, B. W.

    1999-01-01

    Transcranial motor evoked potentials (tc-MEPs) are used to monitor spinal cord integrity intraoperatively. We compared myogenic motor evoked responses with electrical and magnetic transcranial stimuli during nitrous oxide/opioid anesthesia. In 11 patients undergoing spinal surgery, anesthesia was

  1. Lifting the veil on the dynamics of neuronal activities evoked by transcranial magnetic stimulation.

    Science.gov (United States)

    Li, Bingshuo; Virtanen, Juha P; Oeltermann, Axel; Schwarz, Cornelius; Giese, Martin A; Ziemann, Ulf; Benali, Alia

    2017-11-22

    Transcranial magnetic stimulation (TMS) is a widely used non-invasive tool to study and modulate human brain functions. However, TMS-evoked activity of individual neurons has remained largely inaccessible due to the large TMS-induced electromagnetic fields. Here, we present a general method providing direct in vivo electrophysiological access to TMS-evoked neuronal activity 0.8-1 ms after TMS onset. We translated human single-pulse TMS to rodents and unveiled time-grained evoked activities of motor cortex layer V neurons that show high-frequency spiking within the first 6 ms depending on TMS-induced current orientation and a multiphasic spike-rhythm alternating between excitation and inhibition in the 6-300 ms epoch, all of which can be linked to various human TMS responses recorded at the level of spinal cord and muscles. The advance here facilitates a new level of insight into the TMS-brain interaction that is vital for developing this non-invasive tool to purposefully explore and effectively treat the human brain.

  2. Head movements evoked in alert rhesus monkey by vestibular prosthesis stimulation: implications for postural and gaze stabilization.

    Directory of Open Access Journals (Sweden)

    Diana E Mitchell

    Full Text Available The vestibular system detects motion of the head in space and in turn generates reflexes that are vital for our daily activities. The eye movements produced by the vestibulo-ocular reflex (VOR play an essential role in stabilizing the visual axis (gaze, while vestibulo-spinal reflexes ensure the maintenance of head and body posture. The neuronal pathways from the vestibular periphery to the cervical spinal cord potentially serve a dual role, since they function to stabilize the head relative to inertial space and could thus contribute to gaze (eye-in-head + head-in-space and posture stabilization. To date, however, the functional significance of vestibular-neck pathways in alert primates remains a matter of debate. Here we used a vestibular prosthesis to 1 quantify vestibularly-driven head movements in primates, and 2 assess whether these evoked head movements make a significant contribution to gaze as well as postural stabilization. We stimulated electrodes implanted in the horizontal semicircular canal of alert rhesus monkeys, and measured the head and eye movements evoked during a 100 ms time period for which the contribution of longer latency voluntary inputs to the neck would be minimal. Our results show that prosthetic stimulation evoked significant head movements with latencies consistent with known vestibulo-spinal pathways. Furthermore, while the evoked head movements were substantially smaller than the coincidently evoked eye movements, they made a significant contribution to gaze stabilization, complementing the VOR to ensure that the appropriate gaze response is achieved. We speculate that analogous compensatory head movements will be evoked when implanted prosthetic devices are transitioned to human patients.

  3. Biomarkers of neuropathic pain in skin nerve degeneration neuropathy: contact heat-evoked potentials as a physiological signature.

    Science.gov (United States)

    Wu, Shao-Wei; Wang, Yi-Chia; Hsieh, Paul-Chen; Tseng, Ming-Tsung; Chiang, Ming-Chang; Chu, Chih-Pang; Feng, Fang-Ping; Lin, Yea-Huey; Hsieh, Sung-Tsang; Chao, Chi-Chao

    2017-03-01

    Contact heat-evoked potentials (CHEPs) have become an established method of assessing small-fiber sensory nerves; however, their potential as a physiological signature of neuropathic pain symptoms has not been fully explored. To investigate the diagnostic efficacy in examining small-fiber sensory nerve degeneration, the relationship with skin innervations, and clinical correlates with sensory symptoms, we recruited 188 patients (115 men) with length-dependent sensory symptoms and reduced intraepidermal nerve fiber (IENF) density at the distal leg to perform CHEP, quantitative sensory testing, and nerve conduction study. Fifty-seven age- and sex-matched controls were enrolled for comparison of CHEP and skin innervation. Among patients with neuropathy, 144 patients had neuropathic pain and 64 cases had evoked pain. Compared with quantitative sensory testing and nerve conduction study parameters, CHEP amplitudes showed the highest sensitivity for diagnosing small-fiber sensory nerve degeneration and exhibited the strongest correlation with IENF density in multiple linear regression. Contact heat-evoked potential amplitudes were strongly correlated with the degree of skin innervation in both patients with neuropathy and controls, and the slope of the regression line between CHEP amplitude and IENF density was higher in patients with neuropathy than in controls. Patients with evoked pain had higher CHEP amplitude than those without evoked pain, independent of IENF density. Receiver operating characteristic analysis showed that CHEP had better performance in diagnosing small-fiber sensory nerve degeneration than thermal thresholds. Furthermore, CHEPs showed superior classification accuracy with respect to evoked pain. In conclusion, CHEP is a sensitive tool to evaluate pathophysiology of small-fiber sensory nerve and serves as a physiological signature of neuropathic pain symptoms.

  4. Short-interval and long-interval intracortical inhibition of TMS-evoked EEG potentials.

    Science.gov (United States)

    Premoli, Isabella; Király, Julia; Müller-Dahlhaus, Florian; Zipser, Carl M; Rossini, Pierre; Zrenner, Christoph; Ziemann, Ulf; Belardinelli, Paolo

    2018-03-15

    Inhibition in the human motor cortex can be probed by means of paired-pulse transcranial magnetic stimulation (ppTMS) at interstimulus intervals of 2-3 ms (short-interval intracortical inhibition, SICI) or ∼100 ms (long-interval intracortical inhibition, LICI). Conventionally, SICI and LICI are recorded as motor evoked potential (MEP) inhibition in the hand muscle. Pharmacological experiments indicate that they are mediated by GABAA and GABAB receptors, respectively. SICI and LICI of TMS-evoked EEG potentials (TEPs) and their pharmacological properties have not been systematically studied. Here, we sought to examine SICI by ppTMS-evoked compared to single-pulse TMS-evoked TEPs, to investigate its pharmacological manipulation and to compare SICI with our previous results on LICI. PpTMS-EEG was applied to the left motor cortex in 16 healthy subjects in a randomized, double-blind placebo-controlled crossover design, testing the effects of a single oral dose 20 mg of diazepam, a positive modulator at the GABAA receptor, vs. 50 mg of the GABAB receptor agonist baclofen on SICI of TEPs. We found significant SICI of the N100 and P180 TEPs prior to drug intake. Diazepam reduced SICI of the N100 TEP, while baclofen enhanced it. Compared to our previous ppTMS-EEG results on LICI, the SICI effects on TEPs, including their drug modulation, were largely analogous. Findings suggest a similar interaction of paired-pulse effects on TEPs irrespective of the interstimulus interval. Therefore, SICI and LICI as measured with TEPs cannot be directly derived from SICI and LICI measured with MEPs, but may offer novel insight into paired-pulse responses recorded directly from the brain rather than muscle. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Sex differences in the jealousy-evoking effect of rival characteristics

    NARCIS (Netherlands)

    Dijkstra, P; Buunk, BP; Buunk, Abraham (Bram)

    2002-01-01

    Four studies examined sex differences in the jealousy-evoking nature of rival characteristics. Study 1, among 130 undergraduates, made an inventory of all relevant rival characteristics that were spontaneously mentioned when asked about a rival to whom one's partner might feel attracted. On the

  6. Effects of Ketamine and Ketamine Metabolites on Evoked Striatal Dopamine Release, Dopamine Receptors, and Monoamine Transporters

    Science.gov (United States)

    Can, Adem; Zanos, Panos; Moaddel, Ruin; Kang, Hye Jin; Dossou, Katinia S. S.; Wainer, Irving W.; Cheer, Joseph F.; Frost, Douglas O.; Huang, Xi-Ping

    2016-01-01

    Following administration at subanesthetic doses, (R,S)-ketamine (ketamine) induces rapid and robust relief from symptoms of depression in treatment-refractory depressed patients. Previous studies suggest that ketamine’s antidepressant properties involve enhancement of dopamine (DA) neurotransmission. Ketamine is rapidly metabolized to (2S,6S)- and (2R,6R)-hydroxynorketamine (HNK), which have antidepressant actions independent of N-methyl-d-aspartate glutamate receptor inhibition. These antidepressant actions of (2S,6S;2R,6R)-HNK, or other metabolites, as well as ketamine’s side effects, including abuse potential, may be related to direct effects on components of the dopaminergic (DAergic) system. Here, brain and blood distribution/clearance and pharmacodynamic analyses at DA receptors (D1–D5) and the DA, norepinephrine, and serotonin transporters were assessed for ketamine and its major metabolites (norketamine, dehydronorketamine, and HNKs). Additionally, we measured electrically evoked mesolimbic DA release and decay using fast-scan cyclic voltammetry following acute administration of subanesthetic doses of ketamine (2, 10, and 50 mg/kg, i.p.). Following ketamine injection, ketamine, norketamine, and multiple hydroxynorketamines were detected in the plasma and brain of mice. Dehydronorketamine was detectable in plasma, but concentrations were below detectable limits in the brain. Ketamine did not alter the magnitude or kinetics of evoked DA release in the nucleus accumbens in anesthetized mice. Neither ketamine’s enantiomers nor its metabolites had affinity for DA receptors or the DA, noradrenaline, and serotonin transporters (up to 10 μM). These results suggest that neither the side effects nor antidepressant actions of ketamine or ketamine metabolites are associated with direct effects on mesolimbic DAergic neurotransmission. Previously observed in vivo changes in DAergic neurotransmission following ketamine administration are likely indirect. PMID

  7. Pharmacology of morphine and morphine-3-glucuronide at opioid, excitatory amino acid, GABA and glycine binding sites

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    Bartlett, S.E.; Smith, M.T. (Department of Pharmacy, The University of Queensland (Australia)); Dood, P.R. (Clinical Research Centre, Royal Brisbane Hospital Foundation, Brisbane (Australia))

    1994-07-01

    Morphine in high doses and its major metabolite, morphine-3-glucuronide, cause CNS excitation following intrathecal and intracerebroventricular administration by an unknown mechanism. This study investigated whether morphine and morphine-3-glucuronide interact at major excitatory (glutamate), major inhibitory (GABA or glycine), or opioid binding sites. Homogenate binding assays were performed using specific radioligands. At opioid receptors, morphine-3-glucuronide and morphine caused an equipotent sodium shift, consistent with morphine-3-glucuronide behaving as an agonist. This suggests that morphine-3-glucuronide-mediated excitation is not caused by an interaction at opioid receptors. Morphine-3-glucuronide and morphine caused a weak inhibition of the binding of [sup 3]H-MK801 (non-competitive antagonist) and [sup 125]I-ifenprodil (polyamine site antagonist), but at unphysiologically high concentrations. This suggests that CNS excitation would not result from an interaction of morphine-3-glucuronide and high-dose morphine with these sites on the NMDA receptor. Morphine-3-glucuronide and morphine inhibited the binding of [sup 3]H-muscimol (GABA receptor agonist), [sup 3]H-diazepam and [sup 3]H-flunitraxepam (benzodiazepine agonists) binding very weakly, suggesting the excitatory effects of morphine-3-glucuronide and high-dose morphine are not elicited through GABA[sub A] receptors. Morphine-3-glucuronide and high-dose morphine did not prevent re-uptake of glutamate into presynaptic nerve terminals. In addition, morphine-3-glucuronide and morphine did not inhibit the binding of [sup 3]H-strychnine (glycine receptor antagonist) to synaptic membranes prepared from bovine spinal cord. It is concluded that excitation caused by high-dose morphine and morphine-3-glucuronide is not mediated by an interaction with postsynaptic amino acid receptors. (au) (30 refs.).

  8. A translational study on looming-evoked defensive response and the underlying subcortical pathway in autism.

    Science.gov (United States)

    Hu, Yu; Chen, Zhuoming; Huang, Lu; Xi, Yue; Li, Bingxiao; Wang, Hong; Yan, Jiajian; Lee, Tatia M C; Tao, Qian; So, Kwok-Fai; Ren, Chaoran

    2017-11-07

    Rapidly approaching objects indicating threats can induce defensive response through activating a subcortical pathway comprising superior colliculus (SC), lateral posterior nucleus (LP), and basolateral amygdala (BLA). Abnormal defensive response has been reported in autism, and impaired synaptic connections could be the underlying mechanism. Whether the SC-LP-BLA pathway processes looming stimuli abnormally in autism is not clear. Here, we found that looming-evoked defensive response is impaired in a subgroup of the valproic acid (VPA) mouse model of autism. By combining the conventional neurotracer and transneuronal rabies virus tracing techniques, we demonstrated that synaptic connections in the SC-LP-BLA pathway were abnormal in VPA mice whose looming-evoked defensive responses were absent. Importantly, we further translated the finding to children with autism and observed that they did not present looming-evoked defensive response. Furthermore, the findings of the DTI with the probabilistic tractography showed that the structural connections of SC-pulvinar-amygdala in autism children were weak. The pulvinar is parallel to the LP in a mouse. Because looming-evoked defensive response is innate in humans and emerges much earlier than do social and language functions, the absence of defensive response could be an earlier sign of autism in children.

  9. Inhibition of histone deacetylase 3 via RGFP966 facilitates cortical plasticity underlying unusually accurate auditory associative cue memory for excitatory and inhibitory cue-reward associations.

    Science.gov (United States)

    Shang, Andrea; Bylipudi, Sooraz; Bieszczad, Kasia M

    2018-05-31

    Epigenetic mechanisms are key for regulating long-term memory (LTM) and are known to exert control on memory formation in multiple systems of the adult brain, including the sensory cortex. One epigenetic mechanism is chromatin modification by histone acetylation. Blocking the action of histone de-acetylases (HDACs) that normally negatively regulate LTM by repressing transcription, has been shown to enable memory formation. Indeed, HDAC-inhibition appears to facilitate memory by altering the dynamics of gene expression events important for memory consolidation. However less understood are the ways in which molecular-level consolidation processes alter subsequent memory to enhance storage or facilitate retrieval. Here we used a sensory perspective to investigate whether the characteristics of memory formed with HDAC inhibitors are different from naturally-formed memory. One possibility is that HDAC inhibition enables memory to form with greater sensory detail than normal. Because the auditory system undergoes learning-induced remodeling that provides substrates for sound-specific LTM, we aimed to identify behavioral effects of HDAC inhibition on memory for specific sound features using a standard model of auditory associative cue-reward learning, memory, and cortical plasticity. We found that three systemic post-training treatments of an HDAC3-inhibitor (RGPF966, Abcam Inc.) in rats in the early phase of training facilitated auditory discriminative learning, changed auditory cortical tuning, and increased the specificity for acoustic frequency formed in memory of both excitatory (S+) and inhibitory (S-) associations for at least 2 weeks. The findings support that epigenetic mechanisms act on neural and behavioral sensory acuity to increase the precision of associative cue memory, which can be revealed by studying the sensory characteristics of long-term associative memory formation with HDAC inhibitors. Published by Elsevier B.V.

  10. Role of Active Listening and Listening Effort on Contralateral Suppression of Transient Evoked Otoacousic Emissions

    OpenAIRE

    Kalaiah, Mohan Kumar; Theruvan, Nikhitha B; Kumar, Kaushlendra; Bhat, Jayashree S

    2017-01-01

    Background and Objectives The present study aimed to investigate the effect of active listening and listening effort on the contralateral suppression of transient evoked otoacoustic emissions (CSTEOAEs). Subjects and Methods Twenty eight young adults participated in the study. Transient evoked otoacoustic emissions (TEOAEs) were recorded using ?linear? clicks at 60 dB peSPL, in three contralateral noise conditions. In condition 1, TEOAEs were obtained in the presence of white noise in the con...

  11. Subregion-specific modulation of excitatory input and dopaminergic output in the striatum by tonically activated glycine and GABAA receptors

    Directory of Open Access Journals (Sweden)

    Louise eAdermark

    2011-10-01

    Full Text Available The flow of cortical information through the basal ganglia is a complex spatiotemporal pattern of increased and decreased firing. The striatum is the biggest input nucleus to the basal ganglia and the aim of this study was to assess the role of inhibitory GABAA and glycine receptors in regulating synaptic activity in the dorsolateral (DLS and ventral striatum (nucleus accumbens, nAc. Local field potential recordings from coronal brain slices of juvenile and adult Wistar rats showed that GABAA receptors and strychnine-sensitive glycine receptors are tonically activated and inhibit excitatory input to the DLS and to the nAc. Strychnine-induced disinhibition of glutamatergic transmission was insensitive to the muscarinic receptor inhibitor scopolamine (10 µM, inhibited by the nicotinic acetylcholine receptor antagonist mecamylamine (10 µM and blocked by GABAA receptor inhibitors, suggesting that tonically activated glycine receptors depress excitatory input to the striatum through modulation of cholinergic and GABAergic neurotransmission. As an end-product example of striatal GABAergic output in vivo we measured dopamine release in the DLS and nAc by microdialysis in the awake and freely moving rat. Reversed dialysis of bicuculline (50 μM in perfusate only increased extrasynaptic dopamine levels in the nAc, while strychnine administered locally (200 μM in perfusate decreased dopamine output by 60% in both the DLS and nAc. Our data suggest that GABAA and glycine receptors are tonically activated and modulate striatal transmission in a partially sub-region specific manner.

  12. "Passie, Hartstocht": Painting and Evoking Emotions in Rembrandt’s Studio

    NARCIS (Netherlands)

    Weststeijn, T.; Fritsche, C.; Leonhard, K.; Weber, G.J.M.

    2013-01-01

    Focusing on Rembrandt’s studio, this chapter explores the theory and practice in the depiction of the passions. It argues that the central importance alotted to portraying and evoking emotions in rhetorical theory inspired painterly experiments in the 1630s and theoretical ideals that were first

  13. Feasibility and performance evaluation of generating and recording visual evoked potentials using ambulatory Bluetooth based system.

    Science.gov (United States)

    Ellingson, Roger M; Oken, Barry

    2010-01-01

    Report contains the design overview and key performance measurements demonstrating the feasibility of generating and recording ambulatory visual stimulus evoked potentials using the previously reported custom Complementary and Alternative Medicine physiologic data collection and monitoring system, CAMAS. The methods used to generate visual stimuli on a PDA device and the design of an optical coupling device to convert the display to an electrical waveform which is recorded by the CAMAS base unit are presented. The optical sensor signal, synchronized to the visual stimulus emulates the brain's synchronized EEG signal input to CAMAS normally reviewed for the evoked potential response. Most importantly, the PDA also sends a marker message over the wireless Bluetooth connection to the CAMAS base unit synchronized to the visual stimulus which is the critical averaging reference component to obtain VEP results. Results show the variance in the latency of the wireless marker messaging link is consistent enough to support the generation and recording of visual evoked potentials. The averaged sensor waveforms at multiple CPU speeds are presented and demonstrate suitability of the Bluetooth interface for portable ambulatory visual evoked potential implementation on our CAMAS platform.

  14. Intrinsic and task-evoked network architectures of the human brain

    Science.gov (United States)

    Cole, Michael W.; Bassett, Danielle S.; Power, Jonathan D.; Braver, Todd S.; Petersen, Steven E.

    2014-01-01

    Summary Many functional network properties of the human brain have been identified during rest and task states, yet it remains unclear how the two relate. We identified a whole-brain network architecture present across dozens of task states that was highly similar to the resting-state network architecture. The most frequent functional connectivity strengths across tasks closely matched the strengths observed at rest, suggesting this is an “intrinsic”, standard architecture of functional brain organization. Further, a set of small but consistent changes common across tasks suggests the existence of a task-general network architecture distinguishing task states from rest. These results indicate the brain’s functional network architecture during task performance is shaped primarily by an intrinsic network architecture that is also present during rest, and secondarily by evoked task-general and task-specific network changes. This establishes a strong relationship between resting-state functional connectivity and task-evoked functional connectivity – areas of neuroscientific inquiry typically considered separately. PMID:24991964

  15. Effect of caffeine on vestibular evoked myogenic potential: a systematic review with meta-analysis.

    Science.gov (United States)

    Souza, Maria Eduarda Di Cavalcanti Alves de; Costa, Klinger Vagner Teixeira da; Menezes, Pedro de Lemos

    2017-12-24

    Caffeine can be considered the most consumed drug by adults worldwide, and can be found in several foods, such as chocolate, coffee, tea, soda and others. Overall, caffeine in moderate doses, results in increased physical and intellectual productivity, increases the capacity of concentration and reduces the time of reaction to sensory stimuli. On the other hand, high doses can cause noticeable signs of mental confusion and error induction in intellectual tasks, anxiety, restlessness, muscle tremors, tachycardia, labyrinthine changes, and tinnitus. Considering that the vestibular evoked myogenic potential is a clinical test that evaluates the muscular response of high intensity auditory stimulation, the present systematic review aimed to analyze the effects of caffeine on vestibular evoked myogenic potential. This study consisted of the search of the following databases: MEDLINE, CENTRAL, ScienceDirect, Scopus, Web of Science, LILACS, SciELO and ClinicalTrials.gov. Additionally, the gray literature was also searched. The search strategy included terms related to intervention (caffeine or coffee consumption) and the primary outcome (vestibular evoked myogenic potential). Based on the 253 potentially relevant articles identified through the database search, only two full-text publications were retrieved for further evaluation, which were maintained for qualitative analysis. Analyzing the articles found, caffeine has no effect on vestibular evoked myogenic potential in normal individuals. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  16. Cranial irradiation alters dendritic spine density and morphology in the hippocampus.

    Directory of Open Access Journals (Sweden)

    Ayanabha Chakraborti

    Full Text Available Therapeutic irradiation of the brain is a common treatment modality for brain tumors, but can lead to impairment of cognitive function. Dendritic spines are sites of excitatory synaptic transmission and changes in spine structure and number are thought to represent a morphological correlate of altered brain functions associated with hippocampal dependent learning and memory. To gain some insight into the temporal and sub region specific cellular changes in the hippocampus following brain irradiation, we investigated the effects of 10 Gy cranial irradiation on dendritic spines in young adult mice. One week or 1 month post irradiation, changes in spine density and morphology in dentate gyrus (DG granule and CA1 pyramidal neurons were quantified using Golgi staining. Our results showed that in the DG, there were significant reductions in spine density at both 1 week (11.9% and 1 month (26.9% after irradiation. In contrast, in the basal dendrites of CA1 pyramidal neurons, irradiation resulted in a significant reduction (18.7% in spine density only at 1 week post irradiation. Analysis of spine morphology showed that irradiation led to significant decreases in the proportion of mushroom spines at both time points in the DG as well as CA1 basal dendrites. The proportions of stubby spines were significantly increased in both the areas at 1 month post irradiation. Irradiation did not alter spine density in the CA1 apical dendrites, but there were significant changes in the proportion of thin and mushroom spines at both time points post irradiation. Although the mechanisms involved are not clear, these findings are the first to show that brain irradiation of young adult animals leads to alterations in dendritic spine density and morphology in the hippocampus in a time dependent and region specific manner.

  17. In vivo high-affinity uptake and axonal transport of D-(2,3-/sup 3/H)aspartate in excitatory neurons

    Energy Technology Data Exchange (ETDEWEB)

    Storm-Mathisen, J.; Wold, J.E. (Oslo Univ. (Norway))

    1981-12-28

    D-(2,3-/sup 3/H)aspartate ((/sup 3/H)D-Asp) at ..mu..M concentrations in Krebs' solution was infused intracerebrally in rats, mice and hamsters. Neuropil sites in the hippocampal formation, septum and neostriatum, known to receive excitatory nerve inputs with glutamate and aspartate as putative transmitters, showed strong autoradiographic labeling after intraventricular infusions. There was evidence for retrograde axonal transport to pyramidal cell bodies in hippocampus CA3 and neocortex. Infusions into the hilus fasciae dentatae led to anterograde axonal transport of (/sup 3/H)D-Asp in the mossy fibers.

  18. Excitatory amino acid transporters EAAT-1 and EAAT-2 in temporal lobe and hippocampus in intractable temporal lobe epilepsy

    DEFF Research Database (Denmark)

    Sarac, Sinan; Afzal, Shoaib; Broholm, Helle

    2009-01-01

    Intractable temporal lobe epilepsy (TLE) is an invalidating disease and many patients are resistant to medical treatment. Increased glutamate concentration has been found in epileptogenic foci and may induce local over-excitation and cytotoxicity; one of the proposed mechanisms involves reduced...... extra-cellular clearance of glutamate by excitatory amino acid transporters (EAAT-1 to EAAT-5). EAAT-1 and EAAT-2 are mainly expressed on astroglial cells for the reuptake of glutamate from the extra-cellular space. We have studied the expression of EAAT-1 and EAAT-2 in the hippocampus and temporal lobe...

  19. [Intraoperative pain stimuli change somatosensory evoked potentials, but not auditory evoked potentials during isoflurane/nitrous oxide anesthesia].

    Science.gov (United States)

    Rundshagen, I; Kochs, E; Bischoff, P; Schulte am Esch, J

    1997-10-01

    Evoked potentials are used for intraoperative monitoring to assess changes of cerebral function. This prospective randomised study assesses the influence of surgical stimulation on midlatency components of somatosensory (SEPs) and auditory evoked potentials (AEPs) in anaesthetised patients. After approval of the Ethics Committee and written informed consent 36 orthopaedic patients (34 +/- 15 y, 73 +/- 14 kg. 1.71 +/- 0.07 m, ASA I-II) were randomly included in the study. Anaesthesia was induced with 1.5 micrograms/kg fentanyl, 0.3 mg/kg etomidate and 0.1 mg/kg vecuronium. The lungs were intubated and patients normoventilated in steady state anaesthesia with isoflurane (end-tidal 0.6%) and 66% nitrous oxide. 18 patients (group 1) were assigned to the SEP group: median nerve stimulation, recording at Erb, C 6 and the contralateral somatosensory cortex (N20, P25, N35) vs Fz. AEPs were recorded in group 2 (n = 18): binaural stimulation, recording at Cz versus linked mastoid (V, Na, Pa, Nb). Recordings were performed during 30 min before the start of surgery (baseline: BL), at skin incision (SURG1) and at the preparation of the periost (SURG2). Heart rate, mean arterial blood pressure, oxygen saturation, endtidal pCO2 and isoflurane (PetISO) concentrations were registered simultaneously. Data were analysed by one-way analysis of variance. Post hoc comparison were made by Mann-Whitney U-Wilcoxon Rank Sum Test with p beats/min) to SURG2 (76 +/- 12 beats/min). Increases of amplitudes of midlatency SEP amplitudes indicate increased nociceptive signal transmission which is not blunted by isoflurane-nitrous oxide anaesthesia. In contrast, unchanged AEPs indicate adequate levels of the hypnotic components of anaesthesia.

  20. Electrical stimulation of the sacral dorsal gray commissure evokes relaxation of the external urethral sphincter in the cat

    NARCIS (Netherlands)

    Blok, Bertil F.M.; Maarseveen, Jos T.P.W.; Holstege, Gert

    1998-01-01

    Stimulation of the pontine micturition center (PMC) results in micturition, i.e. an immediate relaxation of the urethral sphincter and a contraction of the detrusor muscle of the bladder. The PMC generates the bladder contraction by way of a direct excitatory pathway to the parasympathetic bladder

  1. Use of the Stockwell Transform in the Detection of P300 Evoked Potentials with Low-Cost Brain Sensors

    Directory of Open Access Journals (Sweden)

    Alan F. Pérez-Vidal

    2018-05-01

    Full Text Available The evoked potential is a neuronal activity that originates when a stimulus is presented. To achieve its detection, various techniques of brain signal processing can be used. One of the most studied evoked potentials is the P300 brain wave, which usually appears between 300 and 500 ms after the stimulus. Currently, the detection of P300 evoked potentials is of great importance due to its unique properties that allow the development of applications such as spellers, lie detectors, and diagnosis of psychiatric disorders. The present study was developed to demonstrate the usefulness of the Stockwell transform in the process of identifying P300 evoked potentials using a low-cost electroencephalography (EEG device with only two brain sensors. The acquisition of signals was carried out using the Emotiv EPOC® device—a wireless EEG headset. In the feature extraction, the Stockwell transform was used to obtain time-frequency information. The algorithms of linear discriminant analysis and a support vector machine were used in the classification process. The experiments were carried out with 10 participants; men with an average age of 25.3 years in good health. In general, a good performance (75–92% was obtained in identifying P300 evoked potentials.

  2. Effects of MRI on the electrophysiology of the motor cortex: a TMS study

    International Nuclear Information System (INIS)

    Schlamann, Marc; Pietrzyk, T.; Yoon, M.S.; Gerwig, M.; Kastrup, O.; Maderwald, S.; Forsting, M.; Ladd, S.C.; Duisburg-Essen Univ.; Bitz, A.; Ladd, M.E.

    2009-01-01

    The increasing spread of high-field and ultra-high-field MRI scanners encouraged a new discussion on safety aspects of MRI examinations. Earlier studies report altered acoustically evoked potentials. This finding was not able to be confirmed in later studies. In the present study transcranial magnetic stimulation (TMS) was used to evaluate whether motor cortical excitability may be altered following MRI examination even at field strength of 1.5 T. In 12 right-handed male volunteers individual thresholds for motor responses and then the length of the post-excitatory inhibition (silent period) were determined. Subsequently the volunteers were examined in the MRI scanner (Siemens Avanto, 1.5 T) for 63 minutes using gradient and spin echo sequences. MRI examination was immediately followed by another TMS session and a third 10 minutes later. As a control condition, the 12 subjects spent one hour in the scanner without examination and one hour on a couch without the presence of a scanner. After MRI examination, the silent period was significantly lengthened in all 12 subjects and then tended to the initial value after 10 min. Motor thresholds were significantly elevated and then normalized after 10 minutes. No significant effects were found in the control conditions. (orig.)

  3. Effects of MRI on the electrophysiology of the motor cortex: a TMS study; Auswirkungen der Magnetresonanztomografie auf die Elektrophysiologie des motorischen Kortex: eine Studie mit transkranieller Magnetstimulation

    Energy Technology Data Exchange (ETDEWEB)

    Schlamann, Marc; Pietrzyk, T. [Universitaetsklinikum Essen (Germany). Inst. fuer Diagnostische und Interventionelle Radiologie und Neuroradiologie; Yoon, M.S.; Gerwig, M.; Kastrup, O. [Universitaetsklinikum Essen (Germany). Neurologische Klinik; Maderwald, S.; Forsting, M.; Ladd, S.C. [Universitaetsklinikum Essen (Germany). Inst. fuer Diagnostische und Interventionelle Radiologie und Neuroradiologie; Duisburg-Essen Univ. (Germany). Erwin-L.-Hahn-Inst. fuer Magnetresonanz; Bitz, A.; Ladd, M.E. [Duisburg-Essen Univ. (Germany). Erwin-L.-Hahn-Inst. fuer Magnetresonanz

    2009-03-15

    The increasing spread of high-field and ultra-high-field MRI scanners encouraged a new discussion on safety aspects of MRI examinations. Earlier studies report altered acoustically evoked potentials. This finding was not able to be confirmed in later studies. In the present study transcranial magnetic stimulation (TMS) was used to evaluate whether motor cortical excitability may be altered following MRI examination even at field strength of 1.5 T. In 12 right-handed male volunteers individual thresholds for motor responses and then the length of the post-excitatory inhibition (silent period) were determined. Subsequently the volunteers were examined in the MRI scanner (Siemens Avanto, 1.5 T) for 63 minutes using gradient and spin echo sequences. MRI examination was immediately followed by another TMS session and a third 10 minutes later. As a control condition, the 12 subjects spent one hour in the scanner without examination and one hour on a couch without the presence of a scanner. After MRI examination, the silent period was significantly lengthened in all 12 subjects and then tended to the initial value after 10 min. Motor thresholds were significantly elevated and then normalized after 10 minutes. No significant effects were found in the control conditions. (orig.)

  4. Electrophysical properties, synaptic transmission and neuromodulation in serotonergic caudal raphe neurons.

    Science.gov (United States)

    Li, Y W; Bayliss, D A

    1998-06-01

    1. We studied electrophysiological properties, synaptic transmission and modulation by 5-hydroxytryptamine (5-HT) of caudal raphe neurons using whole-cell recording in a neonatal rat brain slice preparation; recorded neurons were identified as serotonergic by post-hoc immunohistochemical detection of tryptophan hydroxylase, the 5-HT-synthesizing enzyme. 2. Serotonergic neurons fired spontaneously (approximately 1 Hz), with maximal steady state firing rates of < 4 Hz. 5-Hydroxytryptamine caused hyperpolarization and cessation of spike activity in these neurons by activating inwardly rectifying K+ conductance via somatodendritic 5-HT1A receptors. 3. Unitary glutamatergic excitatory post-synaptic potentials (EPSP) and currents (EPSC) were evoked in serotonergic neurons by local electrical stimulation. Evoked EPSC were potently inhibited by 5-HT, an effect mediated by presynaptic 5-HT1B receptors. 4. In conclusion, serotonergic caudal raphe neurons are spontaneously active in vitro; they receive prominent glutamatergic synaptic inputs. 5-Hydroxytryptamine regulates serotonergic neuronal activity of the caudal raphe by decreasing spontaneous activity via somatodendritic 5-HT1A receptors and by inhibiting excitatory synaptic transmission onto these neurons via presynaptic 5-HT1B receptors. These local modulatory mechanisms provide multiple levels of feedback autoregulation of serotonergic raphe neurons by 5-HT.

  5. Pharmacology of Bradykinin-Evoked Coughing in Guinea Pigs

    OpenAIRE

    Hewitt, Matthew M.; Adams, Gregory; Mazzone, Stuart B.; Mori, Nanako; Yu, Li; Canning, Brendan J.

    2016-01-01

    Bradykinin has been implicated as a mediator of the acute pathophysiological and inflammatory consequences of respiratory tract infections and in exacerbations of chronic diseases such as asthma. Bradykinin may also be a trigger for the coughing associated with these and other conditions. We have thus set out to evaluate the pharmacology of bradykinin-evoked coughing in guinea pigs. When inhaled, bradykinin induced paroxysmal coughing that was abolished by the bradykinin B2 receptor antagonis...

  6. Sympathetic skin response evoked by laser skin stimulation

    OpenAIRE

    Rossi, P.; Truini, A.; Serrao, M.; Iannetti, G. D.; Parisi, L.; Pozzessere, G.; Cruccu, G.

    2002-01-01

    The objective of this study was to evoke sympathetic skin responses (SSRs) in healthy subjects using laser stimulation and to compare these responses with those induced by conventional electrical stimuli. Twenty healthy subjects were investigated. SSRs were obtained using electrical and laser stimuli delivered to the wrist controlateral to the recording site. The sympathetic sudomotor conduction velocity (SSFCV) was measured in 8 subjects by simultaneously recording the SSR from the hand and ...

  7. Brain stem auditory evoked responses in chronic alcoholics.

    OpenAIRE

    Chan, Y W; McLeod, J G; Tuck, R R; Feary, P A

    1985-01-01

    Brain stem auditory evoked responses (BAERs) were performed on 25 alcoholic patients with Wernicke-Korsakoff syndrome, 56 alcoholic patients without Wernicke-Korsakoff syndrome, 24 of whom had cerebellar ataxia, and 37 control subjects. Abnormal BAERs were found in 48% of patients with Wernicke-Korsakoff syndrome, in 25% of alcoholic patients without Wernicke-Korsakoff syndrome but with cerebellar ataxia, and in 13% of alcoholic patients without Wernicke-Korsakoff syndrome or ataxia. The mean...

  8. Conditioning stimulation techniques for enhancement of transcranially elicited evoked motor responses

    NARCIS (Netherlands)

    Journee, H. -L.; Polak, H. E.; De Kleuver, M.

    2007-01-01

    Introduction. - In spite of the use of multipulse, transcranial electrical stimulation (TES) is still insufficient in a subgroup of patients to elicit motor-evoked potentials during intraoperative neurophysiological monitoring (IONM). Classic facilitation methods used in awake patients are precluded

  9. Functional deficits in peripheral nerve mitochondria in rats with paclitaxel- and oxaliplatin-evoked painful peripheral neuropathy

    OpenAIRE

    Zheng, Huaien; Xiao, Wen Hua; Bennett, Gary J.

    2011-01-01

    Cancer chemotherapeutics like paclitaxel and oxaliplatin produce a dose-limiting chronic sensory peripheral neuropathy that is often accompanied by neuropathic pain. The cause of the neuropathy and pain is unknown. In animal models, paclitaxel-evoked and oxaliplatin-evoked painful peripheral neuropathies are accompanied by an increase in the incidence of swollen and vacuolated mitochondria in peripheral nerve axons. It has been proposed that mitochondrial swelling and vacuolation are indicati...

  10. K+-induced alterations in airway muscle responsiveness to electrical field stimulation

    International Nuclear Information System (INIS)

    Murlas, C.; Ehring, G.; Suszkiw, J.; Sperelakis, N.

    1986-01-01

    We investigated possible pre- and postsynaptic effects of K+-induced depolarization on ferret tracheal smooth muscle (TSM) responsiveness to cholinergic stimulation. To assess electromechanical activity, cell membrane potential (Em) and tension (Tm) were simultaneously recorded in buffer containing 6, 12, 18, or 24 mM K+ before and after electrical field stimulation (EFS) or exogenous acetylcholine (ACh). In 6 mM K+, Em was -58.1 +/- 1.0 mV (mean +/- SE). In 12 mM K+, Em was depolarized to -52.3 +/- 0.9 mV, basal Tm did not change, and both excitatory junctional potentials and contractile responses to EFS at short stimulus duration were larger than in 6 mM K+. No such potentiation occurred at a higher K+, although resting Em and Tm increased progressively above 12 mM K+. The sensitivity of ferret TSM to exogenous ACh appeared unaffected by K+. To determine whether the hyperresponsiveness in 12 mM K+ was due, in part, to augmented ACh release from intramural airway nerves, experiments were done using TSM preparations incubated with [3H]choline to measure [3H]ACh release at rest and during EFS. Although resting [3H]ACh release increased progressively in higher K+, release evoked by EFS was maximal in 12 mM K+ and declined in higher concentrations. We conclude that small elevations in the extracellular K+ concentration augment responsiveness of the airways, by increasing the release of ACh both at rest and during EFS from intramural cholinergic nerve terminals. Larger increases in K+ appear to be inhibitory, possibly due to voltage-dependent effects that occur both pre- and postsynaptically

  11. Lifting the veil on the dynamics of neuronal activities evoked by transcranial magnetic stimulation

    Science.gov (United States)

    Li, Bingshuo; Virtanen, Juha P; Oeltermann, Axel; Schwarz, Cornelius; Giese, Martin A; Ziemann, Ulf

    2017-01-01

    Transcranial magnetic stimulation (TMS) is a widely used non-invasive tool to study and modulate human brain functions. However, TMS-evoked activity of individual neurons has remained largely inaccessible due to the large TMS-induced electromagnetic fields. Here, we present a general method providing direct in vivo electrophysiological access to TMS-evoked neuronal activity 0.8–1 ms after TMS onset. We translated human single-pulse TMS to rodents and unveiled time-grained evoked activities of motor cortex layer V neurons that show high-frequency spiking within the first 6 ms depending on TMS-induced current orientation and a multiphasic spike-rhythm alternating between excitation and inhibition in the 6–300 ms epoch, all of which can be linked to various human TMS responses recorded at the level of spinal cord and muscles. The advance here facilitates a new level of insight into the TMS-brain interaction that is vital for developing this non-invasive tool to purposefully explore and effectively treat the human brain. PMID:29165241

  12. Objective quantification of the tinnitus decompensation by synchronization measures of auditory evoked single sweeps.

    Science.gov (United States)

    Strauss, Daniel J; Delb, Wolfgang; D'Amelio, Roberto; Low, Yin Fen; Falkai, Peter

    2008-02-01

    Large-scale neural correlates of the tinnitus decompensation might be used for an objective evaluation of therapies and neurofeedback based therapeutic approaches. In this study, we try to identify large-scale neural correlates of the tinnitus decompensation using wavelet phase stability criteria of single sweep sequences of late auditory evoked potentials as synchronization stability measure. The extracted measure provided an objective quantification of the tinnitus decompensation and allowed for a reliable discrimination between a group of compensated and decompensated tinnitus patients. We provide an interpretation for our results by a neural model of top-down projections based on the Jastreboff tinnitus model combined with the adaptive resonance theory which has not been applied to model tinnitus so far. Using this model, our stability measure of evoked potentials can be linked to the focus of attention on the tinnitus signal. It is concluded that the wavelet phase stability of late auditory evoked potential single sweeps might be used as objective tinnitus decompensation measure and can be interpreted in the framework of the Jastreboff tinnitus model and adaptive resonance theory.

  13. Comparison of sensitivity of magnetic resonance imaging and evoked potentials in the detection of brainstem involvement in multiple sclerosis

    International Nuclear Information System (INIS)

    Comi, G.; Martinelli, V.; Medaglini, S.; Locatelli, T.; Magnani, G.; Poggi, A.; Triulzi, F.

    1988-01-01

    A comparison was made of the sensitivity of magnetic resonance imaging and the combined use of Brainstem Auditory Evoked Potential and Median Somatosensory Evoked Potential in the detection of brainstem dysfunction in 54 multiple sclerosis patients. 10 refs.; 2 tabs

  14. Role of Autism Susceptibility Gene, CNTNAP2, in Neural Circuitry for Vocal Communication

    Science.gov (United States)

    2013-10-01

    the underlying cause of the action poten- tial attenuation is a global decrease in synaptic transmis- sion. Both excitatory and inhibitory evoked...Alfonsi, M., Mohn, A., Cerbo, R., Guanciali Franchi , P., Fantasia, D., . . . Palka, G. (2012). Mosaic 7q31 deletion involving FOXP2 gene associated...language deficits, accompanied by more global changes in cognitive abilities (Carr et al. 2010; Hamdan et al. 2010; Horn et al. 2010; Pariani et al

  15. Exploring the methods of data analysis in multifocal visual evoked potentials

    DEFF Research Database (Denmark)

    Malmqvist, Lasse; Santiago de Abreu, Lucimar; Fraser, C.

    2016-01-01

    Purpose: The multifocal visual evoked potential (mfVEP) provides a topographical assessment of visual function, which has already shown potential for use in patients with glaucoma and multiple sclerosis. However, the variability in mfVEP measurements has limited its broader application. The purpo...

  16. Genotypic differences in intruder-evoked immediate early gene activation in male, but not female, vasopressin 1b receptor knockout mice.

    Science.gov (United States)

    Witchey, Shannah K; Stevenson, Erica L; Caldwell, Heather K

    2016-11-24

    The neuropeptide arginine vasopressin (Avp) modulates social behaviors via its two centrally expressed receptors, the Avp 1a receptor and the Avp 1b receptor (Avpr1b). Recent work suggests that, at least in mice, Avp signaling through Avpr1b within the CA2 region of the hippocampus is critical for normal aggressive behaviors and social recognition memory. However, this brain area is just one part of a larger neural circuit that is likely to be impacted in Avpr1b knockout (-/-) mice. To identify other brain areas that are affected by altered Avpr1b signaling, genotypic differences in immediate early gene activation, i.e. c-FOS and early growth response factor 1 (EGR-1), were quantified using immunocytochemistry following a single exposure to an intruder. In females, no genotypic differences in intruder-evoked c-FOS or EGR-1 immunoreactivity were observed in any of the brain areas measured. In males, while there were no intruder-evoked genotypic differences in c-FOS immunoreactivity, genotypic differences were observed in EGR-1 immunoreactivity within the ventral bed nucleus of the stria terminalis and the anterior hypothalamus; with Avpr1b -/- males having less EGR-1 immunoreactivity in these regions than controls. These data are the first to identify specific brain areas that may be a part of a neural circuit that includes Avpr1b-expressing cells in the CA2 region of the hippocampus. It is thought that this circuit, when working properly, plays a role in how an animal evaluates its social context.

  17. From cognitive networks to seizures: Stimulus evoked dynamics in a coupled cortical network

    Science.gov (United States)

    Lee, Jaejin; Ermentrout, Bard; Bodner, Mark

    2013-12-01

    Epilepsy is one of the most common neuropathologies worldwide. Seizures arising in epilepsy or in seizure disorders are characterized generally by uncontrolled spread of excitation and electrical activity to a limited region or even over the entire cortex. While it is generally accepted that abnormal excessive firing and synchronization of neuron populations lead to seizures, little is known about the precise mechanisms underlying human epileptic seizures, the mechanisms of transitions from normal to paroxysmal activity, or about how seizures spread. Further complication arises in that seizures do not occur with a single type of dynamics but as many different phenotypes and genotypes with a range of patterns, synchronous oscillations, and time courses. The concept of preventing, terminating, or modulating seizures and/or paroxysmal activity through stimulation of brain has also received considerable attention. The ability of such stimulation to prevent or modulate such pathological activity may depend on identifiable parameters. In this work, firing rate networks with inhibitory and excitatory populations were modeled. Network parameters were chosen to model normal working memory behaviors. Two different models of cognitive activity were developed. The first model consists of a single network corresponding to a local area of the brain. The second incorporates two networks connected through sparser recurrent excitatory connectivity with transmission delays ranging from approximately 3 ms within local populations to 15 ms between populations residing in different cortical areas. The effect of excitatory stimulation to activate working memory behavior through selective persistent activation of populations is examined in the models, and the conditions and transition mechanisms through which that selective activation breaks down producing spreading paroxysmal activity and seizure states are characterized. Specifically, we determine critical parameters and architectural

  18. Task-evoked brain functional magnetic susceptibility mapping by independent component analysis (χICA).

    Science.gov (United States)

    Chen, Zikuan; Calhoun, Vince D

    2016-03-01

    Conventionally, independent component analysis (ICA) is performed on an fMRI magnitude dataset to analyze brain functional mapping (AICA). By solving the inverse problem of fMRI, we can reconstruct the brain magnetic susceptibility (χ) functional states. Upon the reconstructed χ dataspace, we propose an ICA-based brain functional χ mapping method (χICA) to extract task-evoked brain functional map. A complex division algorithm is applied to a timeseries of fMRI phase images to extract temporal phase changes (relative to an OFF-state snapshot). A computed inverse MRI (CIMRI) model is used to reconstruct a 4D brain χ response dataset. χICA is implemented by applying a spatial InfoMax ICA algorithm to the reconstructed 4D χ dataspace. With finger-tapping experiments on a 7T system, the χICA-extracted χ-depicted functional map is similar to the SPM-inferred functional χ map by a spatial correlation of 0.67 ± 0.05. In comparison, the AICA-extracted magnitude-depicted map is correlated with the SPM magnitude map by 0.81 ± 0.05. The understanding of the inferiority of χICA to AICA for task-evoked functional map is an ongoing research topic. For task-evoked brain functional mapping, we compare the data-driven ICA method with the task-correlated SPM method. In particular, we compare χICA with AICA for extracting task-correlated timecourses and functional maps. χICA can extract a χ-depicted task-evoked brain functional map from a reconstructed χ dataspace without the knowledge about brain hemodynamic responses. The χICA-extracted brain functional χ map reveals a bidirectional BOLD response pattern that is unavailable (or different) from AICA. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Click-Evoked Auditory Efferent Activity: Rate and Level Effects.

    Science.gov (United States)

    Boothalingam, Sriram; Kurke, Julianne; Dhar, Sumitrajit

    2018-05-07

    There currently are no standardized protocols to evaluate auditory efferent function in humans. Typical tests use broadband noise to activate the efferents, but only test the contralateral efferent pathway, risk activating the middle ear muscle reflex (MEMR), and are laborious for clinical use. In an attempt to develop a clinical test of bilateral auditory efferent function, we have designed a method that uses clicks to evoke efferent activity, obtain click-evoked otoacoustic emissions (CEOAEs), and monitor MEMR. This allows for near-simultaneous estimation of cochlear and efferent function. In the present study, we manipulated click level (60, 70, and 80 dB peak-equivalent sound pressure level [peSPL]) and rate (40, 50, and 62.5 Hz) to identify an optimal rate-level combination that evokes measurable efferent modulation of CEOAEs. Our findings (n = 58) demonstrate that almost all click levels and rates used caused significant inhibition of CEOAEs, with a significant interaction between level and rate effects. Predictably, bilateral activation produced greater inhibition compared to stimulating the efferents only in the ipsilateral or contralateral ear. In examining the click rate-level effects during bilateral activation in greater detail, we observed a 1-dB inhibition of CEOAE level for each 10-dB increase in click level, with rate held constant at 62.5 Hz. Similarly, a 10-Hz increase in rate produced a 0.74-dB reduction in CEOAE level, with click level held constant at 80 dB peSPL. The effect size (Cohen's d) was small for either monaural condition and medium for bilateral, faster-rate, and higher-level conditions. We were also able to reliably extract CEOAEs from efferent eliciting clicks. We conclude that clicks can indeed be profitably employed to simultaneously evaluate cochlear health using CEOAEs as well as their efferent modulation. Furthermore, using bilateral clicks allows the evaluation of both the crossed and uncrossed elements of the auditory

  20. Auditory- and visual-evoked potentials in Mexican infants are not affected by maternal supplementation with 400 mg/d docosahexaenoic acid in the second half of pregnancy.

    Science.gov (United States)

    Stein, Aryeh D; Wang, Meng; Rivera, Juan A; Martorell, Reynaldo; Ramakrishnan, Usha

    2012-08-01

    The evidence relating prenatal supplementation with DHA to offspring neurological development is limited. We investigated the effect of prenatal DHA supplementation on infant brainstem auditory-evoked responses and visual- evoked potentials in a double-blind, randomized controlled trial in Cuernavaca, Mexico. Pregnant women were supplemented daily with 400 mg DHA or placebo from gestation wk 18-22 through delivery. DHA and placebo groups did not differ in maternal characteristics at randomization or infant characteristics at birth. Brainstem auditory-evoked responses were measured at 1 and 3 mo in 749 and 664 infants, respectively, and visual-evoked potentials were measured at 3 and 6 mo in 679 and 817 infants, respectively. Left-right brainstem auditory-evoked potentials were moderately correlated (range, 0.26-0.43; all P right visual-evoked potentials were strongly correlated (range, 0.79-0.94; all P 0.10). We conclude that DHA supplementation during pregnancy did not influence brainstem auditory-evoked responses at 1 and 3 mo or visual-evoked potentials at 3 and 6 mo.

  1. A comparison of N-methyl-D-aspartate-evoked release of adenosine and [3H]norepinephrine from rat cortical slices

    International Nuclear Information System (INIS)

    Hoehn, K.; Craig, C.G.; White, T.D.

    1990-01-01

    Tetrodotoxin reduced N-methyl-D-aspartate (NMDA)-evoked release of adenosine by 35% but virtually abolished [3H]norepinephrine release. Although [3H]norepinephrine release from rat cortical slices evoked by 500 microM NMDA was abolished by 1.2 mM Mg++, which produces a voltage-sensitive, uncompetitive block of NMDA-channels, adenosine release was increased in the presence of Mg++. Partial depolarization with 12 mM K+ relieved the Mg++ block of 500 microM NMDA-evoked [3H]norepinephrine release but did not affect adenosine release, indicating that a Mg++ requirement for the adenosine release process per se cannot account for this discrepancy. NMDA was 33 times more potent in releasing adenosine than [3H]norepinephrine. At submaximal concentrations of NMDA (10 and 20 microM), adenosine release was augmented in Mg+(+)-free medium. Although a high concentration of the uncompetitive NMDA antagonist MK-801 [(+)-5-methyl-10,11,dihydro-5H-dibenzo[a,d]cyclohepten-5-10-imine maleate] (3 microM) blocked NMDA-evoked release of [3H]norepinephrine and adenosine, a lower concentration (300 nM) decreased NMDA-evoked [3H]norepinephrine release by 66% without affecting adenosine release. These findings suggest that maximal adenosine release occurs when relatively few NMDA receptors are activated, raising the possibility that spare receptors exist for NMDA-evoked adenosine release. Rather than acting as a protectant against excessive NMDA excitation, released adenosine might provide an inhibitory threshold which must be overcome for NMDA-mediated neurotransmission to proceed

  2. Comparison of joint torque evoked with monopolar and tripolar-cuff electrodes.

    Science.gov (United States)

    Tarler, Matthew D; Mortimer, J Thomas

    2003-09-01

    Using a self-sizing spiral-cuff electrode placed on the sciatic nerve of the cat, the joint torque evoked with stimulation applied to contacts in a monopolar configuration was judged to be the same as the torque evoked by stimulation applied to contacts in a tripolar configuration. Experiments were carried out in six acute cat preparations. In each experiment, a 12-contact electrode was placed on the sciatic nerve and used to effect both the monopolar and tripolar electrode configurations. The ankle torque produced by electrically evoked isometric muscle contraction was measured in three dimensions: plantar flexion, internal rotation, and inversion. Based on the recorded ankle torque, qualitative and quantitative comparisons were performed to determine if any significant difference existed in the pattern or order in which motor nerve fibers were recruited. No significant difference was found at a 98% confidence interval in either the recruitment properties or the repeatability of the monopolar and tripolar configurations. Further, isolated activation of single fascicles within the sciatic nerve was observed. Once nerve fibers in a fascicle were activated, recruitment of that fascicle was modulated over the full range before "spill-over" excitation occurred in neighboring fascicles. These results indicate that a four contact, monopolar nerve-cuff electrode is a viable substitute for a 12 contact, tripolar nerve-cuff electrode. The results of this study are also consistent with the hypothesis that multicontact self-sizing spiral-cuff electrodes can be used in motor prostheses to provide selective control of many muscles. These findings should also apply to other neuroprostheses employing-cuff electrodes on nerve trunks.

  3. Inhibition of somatosensory-evoked cortical responses by a weak leading stimulus.

    Science.gov (United States)

    Nakagawa, Kei; Inui, Koji; Yuge, Louis; Kakigi, Ryusuke

    2014-11-01

    We previously demonstrated that auditory-evoked cortical responses were suppressed by a weak leading stimulus in a manner similar to the prepulse inhibition (PPI) of startle reflexes. The purpose of the present study was to investigate whether a similar phenomenon was present in the somatosensory system, and also whether this suppression reflected an inhibitory process. We recorded somatosensory-evoked magnetic fields following stimulation of the median nerve and evaluated the extent by which they were suppressed by inserting leading stimuli at an intensity of 2.5-, 1.5-, 1.1-, or 0.9-fold the sensory threshold (ST) in healthy participants (Experiment 1). The results obtained demonstrated that activity in the secondary somatosensory cortex in the hemisphere contralateral to the stimulated side (cSII) was significantly suppressed by a weak leading stimulus with the intensity larger than 1.1-fold ST. This result implied that the somatosensory system had an inhibitory process similar to that of PPI. We then presented two successive leading stimuli before the test stimulus, and compared the extent of suppression between the test stimulus-evoked responses and those obtained with the second prepulse alone and with two prepulses (first and second) (Experiment 2). When two prepulses were preceded, cSII responses to the second prepulse were suppressed by the first prepulse, whereas the ability of the second prepulse to suppress the test stimulus remained unchanged. These results suggested the presence of at least two individual pathways; response-generating and inhibitory pathways. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. CHRONIC DIETARY EXPOSURE WITH INTERMITTENT SPIKE DOSES OF CHLORPYRIFOS FAILS TO ALTER FLASH OR PATTERN REVERSAL EVOKED POTENTIALS IN RATS.

    Science.gov (United States)

    Human exposure to pesticides is often characterized by chronic low level exposure with intermittent spiked higher exposures. Visual disturbances are often reported following exposure to xenobiotics, and cholinesterase-inhibiting compounds have been reported to alter visual functi...

  5. The involuntary nature of music-evoked autobiographical memories in Alzheimer's disease

    NARCIS (Netherlands)

    El Haj, M.; Fasotti, L.; Allain, P.

    2012-01-01

    The main objective of this paper was to examine the involuntary nature of music-evoked autobiographical memories. For this purpose, young adults, older adults, and patients with a clinical diagnosis of probable Alzheimer’s disease (AD) were asked to remember autobiographical events in two

  6. Oscillations, complex spatiotemporal behavior, and information transport in networks of excitatory and inhibitory neurons

    International Nuclear Information System (INIS)

    Destexhe, A.

    1994-01-01

    Various types of spatiotemporal behavior are described for two-dimensional networks of excitatory and inhibitory neurons with time delayed interactions. It is described how the network behaves as several structural parameters are varied, such as the number of neurons, the connectivity, and the values of synaptic weights. A transition from spatially uniform oscillations to spatiotemporal chaos via intermittentlike behavior is observed. The properties of spatiotemporally chaotic solutions are investigated by evaluating the largest positive Lyapunov exponent and the loss of correlation with distance. Finally, properties of information transport are evaluated during uniform oscillations and spatiotemporal chaos. It is shown that the diffusion coefficient increases significantly in the spatiotemporal phase similar to the increase of transport coefficients at the onset of fluid turbulence. It is proposed that such a property should be seen in other media, such as chemical turbulence or networks of oscillators. The possibility of measuring information transport from appropriate experiments is also discussed

  7. Spatially structured oscillations in a two-dimensional excitatory neuronal network with synaptic depression

    KAUST Repository

    Kilpatrick, Zachary P.

    2009-10-29

    We study the spatiotemporal dynamics of a two-dimensional excitatory neuronal network with synaptic depression. Coupling between populations of neurons is taken to be nonlocal, while depression is taken to be local and presynaptic. We show that the network supports a wide range of spatially structured oscillations, which are suggestive of phenomena seen in cortical slice experiments and in vivo. The particular form of the oscillations depends on initial conditions and the level of background noise. Given an initial, spatially localized stimulus, activity evolves to a spatially localized oscillating core that periodically emits target waves. Low levels of noise can spontaneously generate several pockets of oscillatory activity that interact via their target patterns. Periodic activity in space can also organize into spiral waves, provided that there is some source of rotational symmetry breaking due to external stimuli or noise. In the high gain limit, no oscillatory behavior exists, but a transient stimulus can lead to a single, outward propagating target wave. © Springer Science + Business Media, LLC 2009.

  8. Spatially structured oscillations in a two-dimensional excitatory neuronal network with synaptic depression

    KAUST Repository

    Kilpatrick, Zachary P.; Bressloff, Paul C.

    2009-01-01

    We study the spatiotemporal dynamics of a two-dimensional excitatory neuronal network with synaptic depression. Coupling between populations of neurons is taken to be nonlocal, while depression is taken to be local and presynaptic. We show that the network supports a wide range of spatially structured oscillations, which are suggestive of phenomena seen in cortical slice experiments and in vivo. The particular form of the oscillations depends on initial conditions and the level of background noise. Given an initial, spatially localized stimulus, activity evolves to a spatially localized oscillating core that periodically emits target waves. Low levels of noise can spontaneously generate several pockets of oscillatory activity that interact via their target patterns. Periodic activity in space can also organize into spiral waves, provided that there is some source of rotational symmetry breaking due to external stimuli or noise. In the high gain limit, no oscillatory behavior exists, but a transient stimulus can lead to a single, outward propagating target wave. © Springer Science + Business Media, LLC 2009.

  9. Use of auditory evoked potentials for intra-operative awareness in anesthesia: a consciousness-based conceptual model.

    Science.gov (United States)

    Dong, Xuebao; Suo, Puxia; Yuan, Xin; Yao, Xuefeng

    2015-01-01

    Auditory evoked potentials (AEPs) have been used as a measure of the depth of anesthesia during the intra-operative process. AEPs are classically divided, on the basis of their latency, into first, fast, middle, slow, and late components. The use of auditory evoked potential has been advocated for the assessment of Intra-operative awareness (IOA), but has not been considered seriously enough to universalize it. It is because we have not explored enough the impact of auditory perception and auditory processing on the IOA phenomena as well as on the subsequent psychological impact of IOA on the patient. More importantly, we have seldom tried to look at the phenomena of IOP from the perspective of consciousness itself. This perspective is especially important because many of IOA phenomena exist in the subconscious domain than they do in the conscious domain of explicit recall. Two important forms of these subconscious manifestations of IOA are the implicit recall phenomena and post-operative dreams related to the operation. Here, we present an integrated auditory consciousness-based model of IOA. We start with a brief description of auditory awareness and the factors affecting it. Further, we proceed to the evaluation of conscious and subconscious information processing by auditory modality and how they interact during and after intra-operative period. Further, we show that both conscious and subconscious auditory processing affect the IOA experience and both have serious psychological implications on the patient subsequently. These effects could be prevented by using auditory evoked potential during monitoring of anesthesia, especially the mid-latency auditory evoked potentials (MLAERs). To conclude our model with present hypothesis, we propose that the use of auditory evoked potential should be universal with general anesthesia use in order to prevent the occurrences of distressing outcomes resulting from both conscious and subconscious auditory processing during

  10. Choline evokes fluid secretion by perfused rat mandibular gland without desensitization

    DEFF Research Database (Denmark)

    Murakami, M; Novak, I; Young, J A

    1986-01-01

    M and evoked secretory responses comparable with those of acetylcholine (0.05-1.0 microM) administered at similar Na concentrations. Continuous infusion of choline, in contrast to acetylcholine, did not lead to a fall off in the secretory response (desensitization or tachyphylaxis) until the choline...

  11. Visually-evoked pattern and photomyoclonic responses in video game and television epilepsy: case reports.

    Science.gov (United States)

    Anyanwu, E; Watson, N A

    1996-01-01

    This research paper reports a case study of two male photosensitive epileptic patients, aged 14 and 16 years old respectively, whose epileptic seizures were often triggered by the flickers from television and video games respectively. The 14-year old patient had no family history of epilepsy, while the 16 year old had a family history of epilepsy. A comprehensive electroencephalogram (EEG), including hyperventilation, intermittent photic stimulation (IPS) and pattern stimulation were carried out on them and EEG abnormalities including photoparoxysmal responses (PPR) and generalized myoclonic responses were evoked. A thorough analysis of the EEG morphology of the myclonic responses and the clinical manifestations showed evidence of two separate entitles of seizures namely: visually evoked pattern-myoclonic responses (PTMR) and visually evoked photomyoclonic responses (PMR). PTMR was independent of flash rate and occurred before a PPR and at the same time as the flash rate, while PMR occurred after the PPR and was dependent on flash rate. These findings suggest that "Video Game" epilepsy is probably a pattern sensitive epilepsy, electronic screen being the source of the triggering patterns; hence, the morphology and the family histories and the myoclonic phenomena differ from those of pure photosensitive epilepsy.

  12. Quantifying interhemispheric symmetry of somatosensory evoked potentials with the intraclass correlation coefficient

    NARCIS (Netherlands)

    van de Wassenberg, Wilma J. G.; van der Hoeven, Johannes H.; Leenders, Klaus L.; Maurits, Natasha M.

    Although large intersubject variability is reported for cortical somatosensory evoked potentials (SEPs), variability between hemispheres within one subject is thought to be small. Therefore, interhemispheric comparison of SEP waveforms might be clinically useful to detect unilateral abnormalities in

  13. Rapid binge-like eating and body weight gain driven by zona incerta GABA neuron activation.

    Science.gov (United States)

    Zhang, Xiaobing; van den Pol, Anthony N

    2017-05-26

    The neuronal substrate for binge eating, which can at times lead to obesity, is not clear. We find that optogenetic stimulation of mouse zona incerta (ZI) γ-aminobutyric acid (GABA) neurons or their axonal projections to paraventricular thalamus (PVT) excitatory neurons immediately (in 2 to 3 seconds) evoked binge-like eating. Minimal intermittent stimulation led to body weight gain; ZI GABA neuron ablation reduced weight. ZI stimulation generated 35% of normal 24-hour food intake in just 10 minutes. The ZI cells were excited by food deprivation and the gut hunger signal ghrelin. In contrast, stimulation of excitatory axons from the parasubthalamic nucleus to PVT or direct stimulation of PVT glutamate neurons reduced food intake. These data suggest an unexpected robust orexigenic potential for the ZI GABA neurons. Copyright © 2017, American Association for the Advancement of Science.

  14. Metabolic control of vesicular glutamate transport and release.

    Science.gov (United States)

    Juge, Narinobu; Gray, John A; Omote, Hiroshi; Miyaji, Takaaki; Inoue, Tsuyoshi; Hara, Chiaki; Uneyama, Hisayuki; Edwards, Robert H; Nicoll, Roger A; Moriyama, Yoshinori

    2010-10-06

    Fasting has been used to control epilepsy since antiquity, but the mechanism of coupling between metabolic state and excitatory neurotransmission remains unknown. Previous work has shown that the vesicular glutamate transporters (VGLUTs) required for exocytotic release of glutamate undergo an unusual form of regulation by Cl(-). Using functional reconstitution of the purified VGLUTs into proteoliposomes, we now show that Cl(-) acts as an allosteric activator, and the ketone bodies that increase with fasting inhibit glutamate release by competing with Cl(-) at the site of allosteric regulation. Consistent with these observations, acetoacetate reduced quantal size at hippocampal synapses and suppresses glutamate release and seizures evoked with 4-aminopyridine in the brain. The results indicate an unsuspected link between metabolic state and excitatory neurotransmission through anion-dependent regulation of VGLUT activity. Copyright © 2010 Elsevier Inc. All rights reserved.

  15. Brain state-dependence of electrically evoked potentials monitored with head-mounted electronics.

    Science.gov (United States)

    Richardson, Andrew G; Fetz, Eberhard E

    2012-11-01

    Inferring changes in brain connectivity is critical to studies of learning-related plasticity and stimulus-induced conditioning of neural circuits. In addition, monitoring spontaneous fluctuations in connectivity can provide insight into information processing during different brain states. Here, we quantified state-dependent connectivity changes throughout the 24-h sleep-wake cycle in freely behaving monkeys. A novel, head-mounted electronic device was used to electrically stimulate at one site and record evoked potentials at other sites. Electrically evoked potentials (EEPs) revealed the connectivity pattern between several cortical sites and the basal forebrain. We quantified state-dependent changes in the EEPs. Cortico-cortical EEP amplitude increased during slow-wave sleep, compared to wakefulness, while basal-cortical EEP amplitude decreased. The results demonstrate the utility of using portable electronics to document state-dependent connectivity changes in freely behaving primates.

  16. Longitudinal changes in task-evoked brain responses in Parkinson’s disease patients with and without mild cognitive impairment

    Directory of Open Access Journals (Sweden)

    Urban eEkman

    2014-07-01

    Full Text Available Cognitive deficits are common in Parkinson’s disease. Previous cross-sectional research has demonstrated a link between cognitive impairments and fronto-striatal dopaminergic dysmodulation. However, longitudinal studies that link disease progression with altered task-evoked brain activity are lacking. Therefore, our objective was to longitudinally evaluate working-memory related brain activity changes in Parkinson’s disease patients with and without mild cognitive impairment.Patients were recruited within a longitudinal cohort study of incident patients with idiopathic parkinsonism. We longitudinally (at baseline examination and at 12-months follow-up compared 28 patients with Parkinson’s disease without mild cognitive impairment with 11 patients with Parkinson’s disease and mild cognitive impairment. Functional MRI blood oxygen level dependent signal was measured during a verbal two-back working-memory task. Patients with mild cognitive impairment under-recruited bilateral medial prefrontal cortex, right putamen, and lateral parietal cortex at both time-points (main effect of group: p<0.001, uncorrected. Critically, a significant group-by-time interaction effect (p<0.001, uncorrected was found in the right fusiform gyrus, indicating that working-memory related activity decreased for patients with Parkinson’s disease and mild cognitive impairment between baseline and follow-up, while patients without mild cognitive impairment were stable across time-points. The functional connectivity between right fusiform gyrus and bilateral caudate nucleus was stronger for patients without MCI relative to patients with MCI.Our findings support the view that deficits in working-memory updating are related to persistent fronto-striatal under-recruitments in patients with early phase Parkinson’s disease and mild cognitive impairment. The longitudinal evolution of mild cognitive impairment in Parkinson’s disease translates into additional task-evoked

  17. Neural responses to nostalgia-evoking music modeled by elements of dynamic musical structure and individual differences in affective traits.

    Science.gov (United States)

    Barrett, Frederick S; Janata, Petr

    2016-10-01

    Nostalgia is an emotion that is most commonly associated with personally and socially relevant memories. It is primarily positive in valence and is readily evoked by music. It is also an idiosyncratic experience that varies between individuals based on affective traits. We identified frontal, limbic, paralimbic, and midbrain brain regions in which the strength of the relationship between ratings of nostalgia evoked by music and blood-oxygen-level-dependent (BOLD) signal was predicted by affective personality measures (nostalgia proneness and the sadness scale of the Affective Neuroscience Personality Scales) that are known to modulate the strength of nostalgic experiences. We also identified brain areas including the inferior frontal gyrus, substantia nigra, cerebellum, and insula in which time-varying BOLD activity correlated more strongly with the time-varying tonal structure of nostalgia-evoking music than with music that evoked no or little nostalgia. These findings illustrate one way in which the reward and emotion regulation networks of the brain are recruited during the experiencing of complex emotional experiences triggered by music. These findings also highlight the importance of considering individual differences when examining the neural responses to strong and idiosyncratic emotional experiences. Finally, these findings provide a further demonstration of the use of time-varying stimulus-specific information in the investigation of music-evoked experiences. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Analysis of electrically evoked compound action potential of the auditory nerve in children with bilateral cochlear implants.

    Science.gov (United States)

    Caldas, Fernanda Ferreira; Cardoso, Carolina Costa; Barreto, Monique Antunes de Souza Chelminski; Teixeira, Marina Santos; Hilgenberg, Anacléia Melo da Silva; Serra, Lucieny Silva Martins; Bahmad Junior, Fayez

    2016-01-01

    The cochlear implant device has the capacity to measure the electrically evoked compound action potential of the auditory nerve. The neural response telemetry is used in order to measure the electrically evoked compound action potential of the auditory nerve. To analyze the electrically evoked compound action potential, through the neural response telemetry, in children with bilateral cochlear implants. This is an analytical, prospective, longitudinal, historical cohort study. Six children, aged 1-4 years, with bilateral cochlear implant were assessed at five different intervals during their first year of cochlear implant use. There were significant differences in follow-up time (p=0.0082) and electrode position (p=0.0019) in the T-NRT measure. There was a significant difference in the interaction between time of follow-up and electrode position (p=0.0143) when measuring the N1-P1 wave amplitude between the three electrodes at each time of follow-up. The electrically evoked compound action potential measurement using neural response telemetry in children with bilateral cochlear implants during the first year of follow-up was effective in demonstrating the synchronized bilateral development of the peripheral auditory pathways in the studied population. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  19. Assessment of visual disability using visual evoked potentials.

    Science.gov (United States)

    Jeon, Jihoon; Oh, Seiyul; Kyung, Sungeun

    2012-08-06

    The purpose of this study is to validate the use of visual evoked potential (VEP) to objectively quantify visual acuity in normal and amblyopic patients, and determine if it is possible to predict visual acuity in disability assessment to register visual pathway lesions. A retrospective chart review was conducted of patients diagnosed with normal vision, unilateral amblyopia, optic neuritis, and visual disability who visited the university medical center for registration from March 2007 to October 2009. The study included 20 normal subjects (20 right eyes: 10 females, 10 males, ages 9-42 years), 18 unilateral amblyopic patients (18 amblyopic eyes, ages 19-36 years), 19 optic neuritis patients (19 eyes: ages 9-71 years), and 10 patients with visual disability having visual pathway lesions. Amplitude and latencies were analyzed and correlations with visual acuity (logMAR) were derived from 20 normal and 18 amblyopic subjects. Correlation of VEP amplitude and visual acuity (logMAR) of 19 optic neuritis patients confirmed relationships between visual acuity and amplitude. We calculated the objective visual acuity (logMAR) of 16 eyes from 10 patients to diagnose the presence or absence of visual disability using relations derived from 20 normal and 18 amblyopic eyes. Linear regression analyses between amplitude of pattern visual evoked potentials and visual acuity (logMAR) of 38 eyes from normal (right eyes) and amblyopic (amblyopic eyes) subjects were significant [y = -0.072x + 1.22, x: VEP amplitude, y: visual acuity (logMAR)]. There were no significant differences between visual acuity prediction values, which substituted amplitude values of 19 eyes with optic neuritis into function. We calculated the objective visual acuity of 16 eyes of 10 patients to diagnose the presence or absence of visual disability using relations of y = -0.072x + 1.22 (-0.072). This resulted in a prediction reference of visual acuity associated with malingering vs. real

  20. Nootropic agents enhance the recruitment of fast GABAA inhibition in rat neocortex.

    Science.gov (United States)

    Ling, Douglas S F; Benardo, Larry S

    2005-07-01

    It is widely believed that nootropic (cognition-enhancing) agents produce their therapeutic effects by augmenting excitatory synaptic transmission in cortical circuits, primarily through positive modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate receptors (AMPARs). However, GABA-mediated inhibition is also critical for cognition, and enhanced GABA function may be likewise therapeutic for cognitive disorders. Could nootropics act through such a mechanism as well? To address this question, we examined the effects of nootropic agents on excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) recorded from layer V pyramidal cells in acute slices of somatosensory cortex. Aniracetam, a positive modulator of AMPA/kainate receptors, increased the peak amplitude of evoked EPSCs and the amplitude and duration of polysynaptic fast IPSCs, manifested as a greater total charge carried by IPSCs. As a result, the EPSC/IPSC ratio of total charge was decreased, representing a shift in the excitation-inhibition balance that favors inhibition. Aniracetam did not affect the magnitude of either monosynaptic IPSCs (mono-IPSCs) recorded in the presence of excitatory amino acid receptor antagonists, or miniature IPSCs (mIPSCs) recorded in the presence of tetrodotoxin. However, the duration of both mono-IPSCs and mIPSCs was prolonged, suggesting that aniracetam also directly modulates GABAergic transmission. Cyclothiazide, a preferential modulator of AMPAR function, enhanced the magnitude and duration of polysynaptic IPSCs, similar to aniracetam, but did not affect mono-IPSCs. Concanavalin A, a kainate receptor modulator, had little effect on EPSCs or IPSCs, suggesting there was no contribution from kainate receptor activity. These findings indicate that AMPAR modulators strengthen inhibition in neocortical pyramidal cells, most likely by altering the kinetics of AMPARs on synaptically connected interneurons and possibly by modulating GABA(A) receptor responses