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Sample records for evokes excitatory alterations

  1. Slow excitatory synaptic potentials evoked by distension in myenteric descending interneurones of guinea-pig ileum

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    Thornton, P D J; Bornstein, J C

    2002-01-01

    The functional significance of the slow excitatory synaptic potentials (EPSPs) in myenteric neurones is unknown. We investigated this using intracellular recording from myenteric neurones in guinea-pig ileum, in vitro. In all, 121 neurones responded with fast EPSPs to distension of the intestine oral to the recording site. In 28 of these neurones, distension also evoked depolarizations similar to the slow EPSPs evoked by electrical stimulation in the same neurones. Intracellular injection of biocytin and immunohistochemistry revealed that neurones responding to distension with slow EPSPs were descending interneurones, which were immunoreactive for nitric oxide synthase (NOS). Other neurones, including inhibitory motor neurones and interneurones lacking NOS, did not respond to distension with slow EPSPs, but many had slow EPSPs evoked electrically. Slow EPSPs evoked electrically or by distension in NOS-immunoreactive descending interneurones were resistant to blockade of NK1 or NK3 tachykinin receptors (SR 140333, 100 nm; SR 142801, 100 nm, respectively) and group I metabotropic glutamate receptors (PHCCC, 10–30 μm), when the antagonists were applied in the recording chamber of a two-chambered organ bath. However, slow EPSPs evoked electrically in inhibitory motor neurones were substantially depressed by SR 140333 (100 nm). Blockade of synaptic transmission in the stimulation chamber of the organ bath abolished slow EPSPs evoked by distension, indicating that they arose from activity in interneurones, and not from anally directed, intrinsic sensory neurones. Thus, distension evokes slow EPSPs in a subset of myenteric neurones, which may be important for intestinal motility. PMID:11882690

  2. Layer 3 Excitatory and Inhibitory Circuitry in the Prefrontal Cortex: Developmental Trajectories and Alterations in Schizophrenia.

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    Hoftman, Gil D; Datta, Dibyadeep; Lewis, David A

    2017-05-15

    Convergent evidence suggests that schizophrenia is a disorder of neurodevelopment with alterations in both early and late developmental processes hypothesized to contribute to the disease process. Abnormalities in certain clinical features of schizophrenia, such as working memory impairments, depend on distributed neural circuitry including the dorsolateral prefrontal cortex (DLPFC) and appear to arise during the protracted maturation of this circuitry across childhood and adolescence. In particular, the neural circuitry substrate for working memory in primates involves the coordinated activity of excitatory pyramidal neurons and a specific population of inhibitory gamma-aminobutyric acid neurons (i.e., parvalbumin-containing basket cells) in layer 3 of the DLPFC. Understanding the relationships between the normal development of-and the schizophrenia-associated alterations in-the DLPFC circuitry that subserves working memory could provide new insights into the nature of schizophrenia as a neurodevelopmental disorder. Consequently, we review the following in this article: 1) recent findings regarding alterations of DLPFC layer 3 circuitry in schizophrenia, 2) the developmental refinements in this circuitry that occur during the period when the working memory alterations in schizophrenia appear to arise and progress, and 3) how various adverse environmental exposures could contribute to developmental disturbances of this circuitry in individuals with schizophrenia. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  3. Adolescent chronic mild stress alters hippocampal CB1 receptor-mediated excitatory neurotransmission and plasticity.

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    Reich, C G; Mihalik, G R; Iskander, A N; Seckler, J C; Weiss, M S

    2013-12-03

    Endocannabinoids (eCBs) are involved in the stress response and alterations in eCB signaling may contribute to the etiology of mood disorders. Exposure to chronic mild stress (CMS), a model of depression, produces downregulation of the cannabinoid 1 (CB1) receptor in the hippocampus of male rats. However, it is unknown how this stress-induced change in CB1 levels affects eCB-mediated neurotransmission. In vitro, field potential recordings from CMS-exposed (21-days) rats were performed to assess the effects of stress on eCB-regulated glutamatergic neurotransmission in/on hippocampal area CA1. We observed that application of the CB1 agonist, WIN 55,212-5 (1 μM), in stress animals resulted in a ∼135% increase in excitatory neurotransmission, whereas CB1 activation in non-stress animals leads to a ∼30% decrease. However, during blockade of GABA(A) neurotransmission with picrotoxin, CB1 activation yielded a ∼35% decrease in stress animals. These findings indicate that CMS does not directly affect glutamatergic neurotransmission. Rather, CMS sensitizes CB1 function on GABAergic terminals, leading to less inhibition and an increase in excitatory neurotransmission. This finding is reinforced in that induction of weak long-term-potentiation (LTP) is enhanced in CMS-exposed animals compared to controls and this enhancement is CB1-dependent. Lastly, we observed that the LTP-blocking property of WIN 55,212-5 shifts from being glutamate-dependent in non-stress animals to being GABA-dependent in stress animals. These results effectively demonstrate that CMS significantly alters hippocampal eCB-mediated neurotransmission and synaptic plasticity. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  4. Prenatal Ethanol Exposure Persistently Alters Endocannabinoid Signaling and Endocannabinoid-Mediated Excitatory Synaptic Plasticity in Ventral Tegmental Area Dopamine Neurons.

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    Hausknecht, Kathryn; Shen, Ying-Ling; Wang, Rui-Xiang; Haj-Dahmane, Samir; Shen, Roh-Yu

    2017-06-14

    Prenatal ethanol exposure (PE) leads to increased addiction risk which could be mediated by enhanced excitatory synaptic strength in ventral tegmental area (VTA) dopamine (DA) neurons. Previous studies have shown that PE enhances excitatory synaptic strength by facilitating an anti-Hebbian form of long-term potentiation (LTP). In this study, we investigated the effect of PE on endocannabinoid-mediated long-term depression (eCB-LTD) in VTA DA neurons. Rats were exposed to moderate (3 g/kg/d) or high (6 g/kg/d) levels of ethanol during gestation. Whole-cell recordings were conducted in male offspring between 4 and 10 weeks old.We found that PE led to increased amphetamine self-administration. Both moderate and high levels of PE persistently reduced low-frequency stimulation-induced eCB-LTD. Furthermore, action potential-independent glutamate release was regulated by tonic eCB signaling in PE animals. Mechanistic studies for impaired eCB-LTD revealed that PE downregulated CB1 receptor function. Interestingly, eCB-LTD in PE animals was rescued by metabotropic glutamate receptor I activation, suggesting that PE did not impair the synthesis/release of eCBs. In contrast, eCB-LTD in PE animals was not rescued by increasing presynaptic activity, which actually led to LTP in PE animals, whereas LTD was still observed in controls. This result shows that the regulation of excitatory synaptic plasticity is fundamentally altered in PE animals. Together, PE leads to impaired eCB-LTD at the excitatory synapses of VTA DA neurons primarily due to CB1 receptor downregulation. This effect could contribute to enhanced LTP and the maintenance of augmented excitatory synaptic strength in VTA DA neurons and increased addiction risk after PE. SIGNIFICANCE STATEMENT Prenatal ethanol exposure (PE) is among many adverse developmental factors known to increase drug addiction risk. Increased excitatory synaptic strength in VTA DA neurons is a critical cellular mechanism for addiction risk. Our

  5. Neurotransmitter alterations in embryonic succinate semialdehyde dehydrogenase (SSADH deficiency suggest a heightened excitatory state during development

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    Snead O Carter

    2008-11-01

    Full Text Available Abstract Background SSADH (aldehyde dehydrogenase 5a1 (Aldh5a1; γ-hydroxybutyric (GHB aciduria deficiency is a defect of GABA degradation in which the neuromodulators GABA and GHB accumulate. The human phenotype is that of nonprogressive encephalopathy with prominent bilateral discoloration of the globi pallidi and variable seizures, the latter displayed prominently in Aldh5a1-/- mice with lethal convulsions. Metabolic studies in murine neural tissue have revealed elevated GABA [and its derivatives succinate semialdehyde (SSA, homocarnosine (HC, 4,5-dihydroxyhexanoic acid (DHHA and guanidinobutyrate (GB] and GHB [and its analogue D-2-hydroxyglutarate (D-2-HG] at birth. Because of early onset seizures and the neurostructural anomalies observed in patients, we examined metabolite features during Aldh5a1-/- embryo development. Methods Embryos were obtained from pregnant dams sacrificed at E (embryo day of life 10–13, 14–15, 16–17, 18–19 and newborn mice. Intact embryos were extracted and metabolites quantified by isotope dilution mass spectrometry (n = 5–15 subjects, Aldh5a1+/+ and Aldh5a1-/- for each gestational age group. Data was evaluated using the t test and one-way ANOVA with Tukey post hoc analysis. Significance was set at the 95th centile. Results GABA and DHHA were significantly elevated at all gestational ages in Aldh5a1-/- mice, while GB was increased only late in gestation; SSA was not elevated at any time point. GHB and D-2-HG increased in an approximately linear fashion with gestational age. Correlative studies in human amniotic fluid from SSADH-deficient pregnancies (n = 5 also revealed significantly increased GABA. Conclusion Our findings indicate early GABAergic alterations in Aldh5a1-/- mice, possibly exacerbated by other metabolites, which likely induce a heightened excitatory state that may predispose neural networks to epilepsy in these animals.

  6. Altered Cortical Dynamics and Cognitive Function upon Haploinsufficiency of the Autism-Linked Excitatory Synaptic Suppressor MDGA2.

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    Connor, Steven A; Ammendrup-Johnsen, Ina; Chan, Allen W; Kishimoto, Yasushi; Murayama, Chiaki; Kurihara, Naokazu; Tada, Atsushi; Ge, Yuan; Lu, Hong; Yan, Ryan; LeDue, Jeffrey M; Matsumoto, Hirotaka; Kiyonari, Hiroshi; Kirino, Yutaka; Matsuzaki, Fumio; Suzuki, Toshiharu; Murphy, Timothy H; Wang, Yu Tian; Yamamoto, Tohru; Craig, Ann Marie

    2016-09-07

    Mutations in a synaptic organizing pathway contribute to autism. Autism-associated mutations in MDGA2 (MAM domain containing glycosylphosphatidylinositol anchor 2) are thought to reduce excitatory/inhibitory transmission. However, we show that mutation of Mdga2 elevates excitatory transmission, and that MDGA2 blocks neuroligin-1 interaction with neurexins and suppresses excitatory synapse development. Mdga2(+/-) mice, modeling autism mutations, demonstrated increased asymmetric synapse density, mEPSC frequency and amplitude, and altered LTP, with no change in measures of inhibitory synapses. Behavioral assays revealed an autism-like phenotype including stereotypy, aberrant social interactions, and impaired memory. In vivo voltage-sensitive dye imaging, facilitating comparison with fMRI studies in autism, revealed widespread increases in cortical spontaneous activity and intracortical functional connectivity. These results suggest that mutations in MDGA2 contribute to altered cortical processing through the dual disadvantages of elevated excitation and hyperconnectivity, and indicate that perturbations of the NRXN-NLGN pathway in either direction from the norm increase risk for autism. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. 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.

  8. Age-related changes in cerebellar and hypothalamic function accompany non-microglial immune gene expression, altered synapse organization, and excitatory amino acid neurotransmission deficits.

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    Bonasera, Stephen J; Arikkath, Jyothi; Boska, Michael D; Chaudoin, Tammy R; DeKorver, Nicholas W; Goulding, Evan H; Hoke, Traci A; Mojtahedzedah, Vahid; Reyelts, Crystal D; Sajja, Balasrinivasa; Schenk, A Katrin; Tecott, Laurence H; Volden, Tiffany A

    2016-09-20

    We describe age-related molecular and neuronal changes that disrupt mobility or energy balance based on brain region and genetic background. Compared to young mice, aged C57BL/6 mice exhibit marked locomotor (but not energy balance) impairments. In contrast, aged BALB mice exhibit marked energy balance (but not locomotor) impairments. Age-related changes in cerebellar or hypothalamic gene expression accompany these phenotypes. Aging evokes upregulation of immune pattern recognition receptors and cell adhesion molecules. However, these changes do not localize to microglia, the major CNS immunocyte. Consistent with a neuronal role, there is a marked age-related increase in excitatory synapses over the cerebellum and hypothalamus. Functional imaging of these regions is consistent with age-related synaptic impairments. These studies suggest that aging reactivates a developmental program employed during embryogenesis where immune molecules guide synapse formation and pruning. Renewed activity in this program may disrupt excitatory neurotransmission, causing significant behavioral deficits.

  9. Altered neural connectivity in excitatory and inhibitory cortical circuits in autism

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    Basilis eZikopoulos

    2013-09-01

    Full Text Available Converging evidence from diverse studies suggests that atypical brain connectivity in autism affects in distinct ways short- and long-range cortical pathways, disrupting neural communication and the balance of excitation and inhibition. This hypothesis is based mostly on functional non-invasive studies that show atypical synchronization and connectivity patterns between cortical areas in children and adults with autism. Indirect methods to study the course and integrity of major brain pathways at low resolution show changes in fractional anisotropy or diffusivity of the white matter in autism. Findings in post-mortem brains of adults with autism provide evidence of changes in the fine structure of axons below prefrontal cortices, which communicate over short- or long-range pathways with other cortices and subcortical structures. Here we focus on evidence of cellular and axon features that likely underlie the changes in short- and long-range communication in autism. We review recent findings of changes in the shape, thickness, and volume of brain areas, cytoarchitecture, neuronal morphology, cellular elements, and structural and neurochemical features of individual axons in the white matter, where pathology is evident even in gross images. We relate cellular and molecular features to imaging and genetic studies that highlight a variety of polymorphisms and epigenetic factors that primarily affect neurite growth and synapse formation and function in autism. We report preliminary findings of changes in autism in the ratio of distinct types of inhibitory neurons in prefrontal cortex, known to shape network dynamics and the balance of excitation and inhibition. Finally we present a model that synthesizes diverse findings by relating them to developmental events, with a goal to identify common processes that perturb development in autism and affect neural communication, reflected in altered patterns of attention, social interactions, and language.

  10. GluA1 Phosphorylation Alters Evoked Firing Pattern In Vivo

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    Balázs Barkóczi

    2012-01-01

    Full Text Available AMPA and NMDA receptors convey fast synaptic transmission in the CNS. Their relative contribution to synaptic output and phosphorylation state regulate synaptic plasticity. The AMPA receptor subunit GluA1 is central in synaptic plasticity. Phosphorylation of GluA1 regulates channel properties and trafficking. The firing rate averaged over several hundred ms is used to monitor cellular input. However, plasticity requires the timing of spiking within a few ms; therefore, it is important to understand how phosphorylation governs these events. Here, we investigate whether the GluA1 phosphorylation (p-GluA1 alters the spiking patterns of CA1 cells in vivo. The antidepressant Tianeptine was used for inducing p-GluA1, which resulted in enhanced AMPA-evoked spiking. By comparing the spiking patterns of AMPA-evoked activity with matched firing rates, we show that the spike-trains after Tianeptine application show characteristic features, distinguishing from spike-trains triggered by strong AMPA stimulation. The interspike-interval distributions are different between the two groups, suggesting that neuronal output may differ when new inputs are activated compared to increasing the gain of previously activated receptors. Furthermore, we also show that NMDA evokes spiking with different patterns to AMPA spike-trains. These results support the role of the modulation of NMDAR/AMPAR ratio and p-GluA1 in plasticity and temporal coding.

  11. The Vestibular-Evoked Postural Response of Adolescents with Idiopathic Scoliosis Is Altered.

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    Jean-Philippe Pialasse

    Full Text Available Adolescent idiopathic scoliosis is a multifactorial disorder including neurological factors. A dysfunction of the sensorimotor networks processing vestibular information could be related to spine deformation. This study investigates whether feed-forward vestibulomotor control or sensory reweighting mechanisms are impaired in adolescent scoliosis patients. Vestibular evoked postural responses were obtained using galvanic vestibular stimulation while participants stood with their eyes closed and head facing forward. Lateral forces under each foot and lateral displacement of the upper body of adolescents with mild (n = 20 or severe (n = 16 spine deformation were compared to those of healthy control adolescents (n = 16. Adolescent idiopathic scoliosis patients demonstrated greater lateral displacement and net lateral forces than controls both during and immediately after vestibular stimulation. Altered sensory reweighting of vestibular and proprioceptive information changed balance control of AIS patients during and after vestibular stimulation. Therefore, scoliosis onset could be related to abnormal sensory reweighting, leading to altered sensorimotor processes.

  12. The neurotoxin 1-methyl-4-phenylpyridinium (MPP+ alters hippocampal excitatory synaptic transmission by modulation of the GABAergic system

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    YuYing eHuang

    2015-08-01

    Full Text Available The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP induces Parkinson’s disease (PD-like symptoms following administration to mice, monkeys and humans. A common view is that MPTP is metabolized to 1-methyl-4-phenylpyridinium ion (MPP+ to induce its neurodegenerative effects on dopaminergic neurons in the substantia nigra. Moreover, the hippocampus contains dopaminergic fibers, which are projecting from the ventral tegmental area, substantia nigra and pars compacta and contain the whole machinery required for dopamine synthesis making them sensitive to MPTP and MPP+. Here we present data showing that acute bath-application of MPP+ elicited a dose-dependent facilitation followed by a depression of synaptic transmission of hippocampal Schaffer collaterals-CA1 synapses in mice. The effects of MPP+ were not mediated by D1/D5- and D2-like receptor activation. Inhibition of the dopamine transporters (DAT did not prevent but increased the depression of excitatory postsynaptic field potentials. In the search for a possible mechanism, we observed that MPP+ reduced the appearance of polyspikes in population spikes recorded in str. pyramidale and increased the frequency of miniature inhibitory postsynaptic currents. The acute effect of MPP+ on synaptic transmission was attenuated by co-application of a GABAA receptor antagonist. Taking these data together, we suggest that MPP+ affects hippocampal synaptic transmission by enhancing some aspects of

  13. Developmental alterations in noxious-evoked EEG activity recorded from rat primary somatosensory cortex.

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    Devonshire, I M; Greenspon, C M; Hathway, G J

    2015-10-01

    Primary somatosensory cortex (S1) contains a nociceptive map that localizes potential tissue damage on the body and encodes stimulus intensity. An objective and specific biomarker of pain however is currently lacking and is urgently required for use in non-verbal clinical populations as well as in the validation of pre-clinical pain models. Here we describe studies to see if the responses of the S1 in juvenile rats are different to those in the adult. We recorded electroencephalogram (EEG) responses from S1 of lightly-anesthetized Sprague-Dawley rats at either postnatal day 21 or postnatal day 40 during the presentation of noxious (55 °C) or innocuous (30 °C) thermal stimuli applied to the plantar surface of the left hindpaw. The total EEG power across the recording period was the same in both ages after stimulation but the frequency distribution was significantly affected by age. Noxious heat evoked a significant increase in theta band (4-8 Hz) activity in adults only (PEEG responses to innocuous thermal stimuli. These data show that there are significant alterations in the processing of nociceptive inputs within the maturing cortex and that cortical theta activity is involved only in the adult cortical response to noxious stimulation. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

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

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    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.

  15. Plasticity of Cortical Excitatory-Inhibitory Balance

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    Froemke, Robert C.

    2015-01-01

    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. PMID:25897875

  16. Interactions between procedural learning and cocaine exposure alter spontaneous and cortically-evoked spike activity in the dorsal striatum

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    Janie eOndracek

    2010-12-01

    Full Text Available We have previously shown that cocaine enhances gene regulation in the sensorimotor striatum associated with procedural learning in a running-wheel paradigm. Here we assessed whether cocaine produces enduring modifications of learning-related changes in striatal neuron activity, using single-unit recordings in anesthetized rats 1 day after the wheel training. Spontaneous and cortically-evoked spike activity was compared between groups treated with cocaine or vehicle immediately prior to the running-wheel training or placement in a locked wheel (control conditions. We found that wheel training in vehicle-treated rats increased the average firing rate of spontaneously active neurons without changing the relative proportion of active to quiescent cells. In contrast, in rats trained under the influence of cocaine, the proportion of spontaneously firing to quiescent cells was significantly greater than in vehicle-treated, trained rats. However, this effect was associated with a lower average firing rate in these spontaneously active cells, suggesting that training under the influence of cocaine recruited additional low-firing cells. Measures of cortically-evoked activity revealed a second interaction between cocaine treatment and wheel training, namely, a cocaine-induced decrease in spike onset latency in control rats (locked wheel. This facilitatory effect of cocaine was abolished when rats trained in the running wheel during cocaine action. These findings highlight important interactions between cocaine and procedural learning, which act to modify population firing activity and the responsiveness of striatal neurons to excitatory inputs. Moreover, these effects were found 24 hours after the training and last drug exposure indicating that cocaine exposure during the learning phase triggers long-lasting changes in synaptic plasticity in the dorsal striatum. Such changes may contribute to the transition from recreational to habitual or compulsive drug

  17. Long latency auditory evoked potentials and central auditory processing in children with reading and writing alterations: Preliminary data

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    Soares, Aparecido José Couto

    2011-10-01

    Full Text Available Introduction: Presently, it is admitted that individuals with reading and writing alterations may present delay in the development of listening skills, which may interfere in the learning process. The assessment of the listening skills can occur in a behavioral way, through central auditory processing (CAP tests, or by electrophysiological assessment highlighting the long latency auditory evoked potentials (LLAEP. The use of the LLAEP as a means of complementary assessment of individuals with reading and writing alterations can become an important data both for further characterization of the alterations, as for the therapeutic guidance of this population. Objective: Characterize the CAP and the LLAEP in children with reading and writing alterations. Method: Research approved by the Institution's Ethic Commission under nº 305/10. The assessment of CAP and LLAEP was performed in 12 children aged between 8 and 12 years old (average of 10,6 years, with reading and writing alterations confirmed in specific evaluation. Results: The most altered CAP skills were temporal ordination and figure-ground for linguistic sounds. There were found altered results in P300 and in MMN. Conclusion: The individuals with reading and writing alterations performed below the expected on CAP tests. The MMN allowed a better characterization of the auditory function of this population. There was evidence of association between the CAP results and the alteration of the LLAEP.

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

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    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…

  19. Evoked corticospinal output to the human scalene muscles is altered by lung volume.

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    Hudson, Anna L; Taylor, Janet L; Anand, Ashima; Gandevia, Simon C; Butler, Jane E

    2012-03-15

    Increases in lung volume inhibit the inspiratory output from the medulla, but the effect of lung inflation on the voluntary control of breathing in humans is not known. We tested corticospinal excitability using transcranial magnetic stimulation (TMS) to evoke a response in the scalene muscles. TMS was delivered at rest at three different lung volumes between functional residual capacity (FRC) and total lung capacity (TLC) during incremental inspiratory and incremental expiratory manoeuvres. Motor evoked potentials (MEPs) in scalenes were ∼50% larger at a high lung volume (FRC+∼90% inspiratory capacity [IC]) compared to lower lung volumes (FRC and FRC+∼40% IC) in both inspiratory and expiratory manoeuvres (plung inflation on the automatic and voluntary control of breathing in humans. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Long-term mTOR inhibitors administration evokes altered calcium homeostasis and platelet dysfunction in kidney transplant patients

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    López, Esther; Berna-Erro, Alejandro; Bermejo, Nuria; Brull, José María; Martinez, Rocío; Garcia Pino, Guadalupe; Alvarado, Raul; Salido, Ginés María; Rosado, Juan Antonio; Cubero, Juan José; Redondo, Pedro Cosme

    2013-01-01

    The use of the mammal target of rapamycin (mTOR) inhibitors has been consolidated as the therapy of election for preventing graft rejection in kidney transplant patients, despite their immunosuppressive activity is less strong than anti-calcineurin agents like tacrolimus and cyclosporine A. Furthermore, as mTOR is widely expressed, rapamycin (a macrolide antibiotic produced by Streptomyces hygroscopicus) is recommended in patients presenting neoplasia due to its antiproliferative actions. Hence, we have investigated whether rapamycin presents side effects in the physiology of other cell types different from leucocytes, such as platelets. Blood samples were drawn from healthy volunteers and kidney transplant patients long-term medicated with rapamycin: sirolimus and everolimus. Platelets were either loaded with fura-2 or directly stimulated, and immunoassayed or fixed with Laemmli's buffer to perform the subsequent analysis of platelet physiology. Our results indicate that rapamycin evokes a biphasic time-dependent alteration in calcium homeostasis and function in platelets from kidney transplant patients under rapamycin regime, as demonstrated by the reduction in granule secretion observed and subsequent impairment of platelet aggregation in these patients compared with healthy volunteers. Platelet count was also reduced in these patients, thus 41% of patients presented thrombocytopenia. All together our results show that long-term administration of rapamycin to kidney transplant patients evokes alteration in platelet function. PMID:23577651

  1. Acute Stress Alters Auditory Selective Attention in Humans Independent of HPA: A Study of Evoked Potentials

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    Elling, Ludger; Steinberg, Christian; Bröckelmann, Ann-Kathrin; Dobel, Christan; Bölte, Jens; Junghofer, Markus

    2011-01-01

    Background Acute stress is a stereotypical, but multimodal response to a present or imminent challenge overcharging an organism. Among the different branches of this multimodal response, the consequences of glucocorticoid secretion have been extensively investigated, mostly in connection with long-term memory (LTM). However, stress responses comprise other endocrine signaling and altered neuronal activity wholly independent of pituitary regulation. To date, knowledge of the impact of such “paracorticoidal” stress responses on higher cognitive functions is scarce. We investigated the impact of an ecological stressor on the ability to direct selective attention using event-related potentials in humans. Based on research in rodents, we assumed that a stress-induced imbalance of catecholaminergic transmission would impair this ability. Methodology/Principal Findings The stressor consisted of a single cold pressor test. Auditory negative difference (Nd) and mismatch negativity (MMN) were recorded in a tonal dichotic listening task. A time series of such tasks confirmed an increased distractibility occuring 4–7 minutes after onset of the stressor as reflected by an attenuated Nd. Salivary cortisol began to rise 8–11 minutes after onset when no further modulations in the event-related potentials (ERP) occurred, thus precluding a causal relationship. This effect may be attributed to a stress-induced activation of mesofrontal dopaminergic projections. It may also be attributed to an activation of noradrenergic projections. Known characteristics of the modulation of ERP by different stress-related ligands were used for further disambiguation of causality. The conjuncture of an attenuated Nd and an increased MMN might be interpreted as indicating a dopaminergic influence. The selective effect on the late portion of the Nd provides another tentative clue for this. Conclusions/Significance Prior studies have deliberately tracked the adrenocortical influence on cognition

  2. Presynaptic transporter-mediated release of glutamate evoked by the protonophore FCCP increases under altered gravity conditions

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    Borisova, T. A.; Krisanova, N. V.

    2008-12-01

    High-affinity Na +-dependent glutamate transporters of the plasma membrane mediate the glutamate uptake into neurons, and thus maintain low levels of extracellular glutamate in the synaptic cleft. The study focused on the release of glutamate by reversal of Na +-dependent glutamate transporters from rat brain nerve terminals (synaptosomes) under conditions of centrifuge-induced hypergravity. Flow cytometric analysis revealed similarity in the size and cytoplasmic granularity between synaptosomal preparations obtained from control and G-loaded animals (10 G, 1 h). The release of cytosolic L-[ 14C]glutamate from synaptosomes was evaluated using the protonophore FCCP, which dissipated synaptic vesicle proton gradient, thus synaptic vesicles were not able to keep glutamate inside and the latter enriched cytosol. FCCP per se induced the greater release of L-[ 14C]glutamate in hypergravity as compared to control (4.8 ± 1.0% and 8.0 ± 1.0% of total label). Exocytotic release of L-[ 14C]glutamate evoked by depolarization was reduced down to zero after FCCP application under both conditions studied. Depolarization stimulated release of cytosolic L-[ 14C]glutamate from synaptosomes preliminary treated with FCCP was considerably increased from 27.0 ± 2.2% of total label in control to 35.0 ± 2.3% in hypergravity. Non-transportable inhibitor of glutamate transporter DL-threo-β-benzyloxyaspartate was found to significantly inhibit high-KCl and FCCP-stimulated release of L-[ 14C]glutamate, confirming the release by reversal of glutamate transporters. The enhancement of transporter-mediated release of glutamate in hypergravity was found to result at least partially from the inhibition of the activity of Na/K-ATPase in the plasma membrane of synaptosomes. We suggested that hypergravity-induced alteration in transporter-mediated release of glutamate indicated hypoxic injury of neurons.

  3. 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

    RATIONALE: Stress-related glucocorticoid and glutamate release have been implicated in hippocampal atrophy evident in patients with post-traumatic stress disorder (PTSD). Glutamatergic mechanisms activate nitric oxide synthase (NOS), while gamma-amino-butyric acid (GABA) may inhibit both...... glutamatergic and nitrergic transmission. Animal studies support a role for NOS in stress. OBJECTIVES: We have studied the role of NOS and glucocorticoids, as well as inhibitory and excitatory transmitters, in a putative animal model of PTSD that emphasizes repeated trauma. METHODS: Hippocampal NOS activity, N......-methyl-D-aspartate (NMDA) receptor binding characteristics and GABA levels were studied in Sprague-Dawley rats 21 days after exposure to a stress-restress paradigm, using radiometric analysis, radioligand studies and high-performance liquid chromatography (HPLC) analysis with electrochemical detection, respectively...

  4. Male-specific alteration in excitatory post-synaptic development and social interaction in pre-natal valproic acid exposure model of autism spectrum disorder.

    Science.gov (United States)

    Kim, Ki Chan; Kim, Pitna; Go, Hyo Sang; Choi, Chang Soon; Park, Jin Hee; Kim, Hee Jin; Jeon, Se Jin; Dela Pena, Ike Campomayor; Han, Seol-Heui; Cheong, Jae Hoon; Ryu, Jong Hoon; Shin, Chan Young

    2013-03-01

    Autism spectrum disorder (ASD) is a pervasive developmental disorder characterized by three main behavioral symptoms including social deficits, impaired communication, and stereotyped and repetitive behaviors. ASD prevalence shows gender bias to male. Prenatal exposure to valproic acid (VPA), a drug used in epilepsy and bipolar disorder, induces autistic symptoms in both human and rodents. As we reported previously, prenatally VPA-exposed animals at E12 showed impairment in social behavior without any overt reproductive toxicity. Social interactions were not significantly different between male and female rats in control condition. However, VPA-exposed male offspring showed significantly impaired social interaction while female offspring showed only marginal deficits in social interaction. Similar male inclination was observed in hyperactivity behavior induced by VPA. In addition to the ASD-like behavioral phenotype, prenatally VPA-exposed rat offspring shows crooked tail phenotype, which was not different between male and female groups. Both male and female rat showed reduced GABAergic neuronal marker GAD and increased glutamatergic neuronal marker vGluT1 expression. Interestingly, despite of the similar increased expression of vGluT1, post-synaptic marker proteins such as PSD-95 and α-CAMKII expression was significantly elevated only in male offspring. Electron microscopy showed increased number of post-synapse in male but not in female at 4 weeks of age. These results might suggest that the altered glutamatergic neuronal differentiation leads to deranged post-synaptic maturation only in male offspring prenatally exposed to VPA. Consistent with the increased post-synaptic compartment, VPA-exposed male rats showed higher sensitivity to electric shock than VPA-exposed female rats. These results suggest that prenatally VPA-exposed rats show the male preponderance of ASD-like behaviors including defective social interaction similar to human autistic patients, which

  5. Prenatal exposure to cannabinoids evokes long-lasting functional alterations by targeting CB1 receptors on developing cortical neurons.

    Science.gov (United States)

    de Salas-Quiroga, Adán; Díaz-Alonso, Javier; García-Rincón, Daniel; Remmers, Floortje; Vega, David; Gómez-Cañas, María; Lutz, Beat; Guzmán, Manuel; Galve-Roperh, Ismael

    2015-11-03

    The CB1 cannabinoid receptor, the main target of Δ(9)-tetrahydrocannabinol (THC), the most prominent psychoactive compound of marijuana, plays a crucial regulatory role in brain development as evidenced by the neurodevelopmental consequences of its manipulation in animal models. Likewise, recreational cannabis use during pregnancy affects brain structure and function of the progeny. However, the precise neurobiological substrates underlying the consequences of prenatal THC exposure remain unknown. As CB1 signaling is known to modulate long-range corticofugal connectivity, we analyzed the impact of THC exposure on cortical projection neuron development. THC administration to pregnant mice in a restricted time window interfered with subcerebral projection neuron generation, thereby altering corticospinal connectivity, and produced long-lasting alterations in the fine motor performance of the adult offspring. Consequences of THC exposure were reminiscent of those elicited by CB1 receptor genetic ablation, and CB1-null mice were resistant to THC-induced alterations. The identity of embryonic THC neuronal targets was determined by a Cre-mediated, lineage-specific, CB1 expression-rescue strategy in a CB1-null background. Early and selective CB1 reexpression in dorsal telencephalic glutamatergic neurons but not forebrain GABAergic neurons rescued the deficits in corticospinal motor neuron development of CB1-null mice and restored susceptibility to THC-induced motor alterations. In addition, THC administration induced an increase in seizure susceptibility that was mediated by its interference with CB1-dependent regulation of both glutamatergic and GABAergic neuron development. These findings demonstrate that prenatal exposure to THC has long-lasting deleterious consequences in the adult offspring solely mediated by its ability to disrupt the neurodevelopmental role of CB1 signaling.

  6. Impaired excitatory drive to spinal GABAergic neurons of neuropathic mice.

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    Jörg Leitner

    Full Text Available Adequate pain sensitivity requires a delicate balance between excitation and inhibition in the dorsal horn of the spinal cord. This balance is severely impaired in neuropathy leading to enhanced pain sensations (hyperalgesia. The underlying mechanisms remain elusive. Here we explored the hypothesis that the excitatory drive to spinal GABAergic neurons might be impaired in neuropathic animals. Transgenic adult mice expressing EGFP under the promoter for GAD67 underwent either chronic constriction injury of the sciatic nerve or sham surgery. In transverse slices from lumbar spinal cord we performed whole-cell patch-clamp recordings from identified GABAergic neurons in lamina II. In neuropathic animals rates of mEPSC were reduced indicating diminished global excitatory input. This downregulation of excitatory drive required a rise in postsynaptic Ca(2+. Neither the density and morphology of dendritic spines on GABAergic neurons nor the number of excitatory synapses contacting GABAergic neurons were affected by neuropathy. In contrast, paired-pulse ratio of Aδ- or C-fiber-evoked monosynaptic EPSCs following dorsal root stimulation was increased in neuropathic animals suggesting reduced neurotransmitter release from primary afferents. Our data indicate that peripheral neuropathy triggers Ca(2+-dependent signaling pathways in spinal GABAergic neurons. This leads to a global downregulation of the excitatory drive to GABAergic neurons. The downregulation involves a presynaptic mechanism and also applies to the excitation of GABAergic neurons by presumably nociceptive Aδ- and C-fibers. This then leads to an inadequately low recruitment of inhibitory interneurons during nociception. We suggest that this previously unrecognized mechanism of impaired spinal inhibition contributes to hyperalgesia in neuropathy.

  7. A different view on the checkerboard? Alterations in early and late visually evoked EEG potentials in Asperger observers.

    Science.gov (United States)

    Kornmeier, Juergen; Wörner, Rike; Riedel, Andreas; Bach, Michael; Tebartz van Elst, Ludger

    2014-01-01

    Asperger Autism is a lifelong psychiatric condition with highly circumscribed interests and routines, problems in social cognition, verbal and nonverbal communication, and also perceptual abnormalities with sensory hypersensitivity. To objectify both lower-level visual and cognitive alterations we looked for differences in visual event-related potentials (EEG) between Asperger observers and matched controls while they observed simple checkerboard stimuli. In a balanced oddball paradigm checkerboards of two checksizes (0.6° and 1.2°) were presented with different frequencies. Participants counted the occurrence times of the rare fine or rare coarse checkerboards in different experimental conditions. We focused on early visual ERP differences as a function of checkerboard size and the classical P3b ERP component as an indicator of cognitive processing. We found an early (100-200 ms after stimulus onset) occipital ERP effect of checkerboard size (dominant spatial frequency). This effect was weaker in the Asperger than in the control observers. Further a typical parietal/central oddball-P3b occurred at 500 ms with the rare checkerboards. The P3b showed a right-hemispheric lateralization, which was more prominent in Asperger than in control observers. The difference in the early occipital ERP effect between the two groups may be a physiological marker of differences in the processing of small visual details in Asperger observers compared to normal controls. The stronger lateralization of the P3b in Asperger observers may indicate a stronger involvement of the right-hemispheric network of bottom-up attention. The lateralization of the P3b signal might be a compensatory consequence of the compromised early checksize effect. Higher-level analytical information processing units may need to compensate for difficulties in low-level signal analysis.

  8. A different view on the checkerboard? Alterations in early and late visually evoked EEG potentials in Asperger observers.

    Directory of Open Access Journals (Sweden)

    Juergen Kornmeier

    Full Text Available BACKGROUND: Asperger Autism is a lifelong psychiatric condition with highly circumscribed interests and routines, problems in social cognition, verbal and nonverbal communication, and also perceptual abnormalities with sensory hypersensitivity. To objectify both lower-level visual and cognitive alterations we looked for differences in visual event-related potentials (EEG between Asperger observers and matched controls while they observed simple checkerboard stimuli. METHODS: In a balanced oddball paradigm checkerboards of two checksizes (0.6° and 1.2° were presented with different frequencies. Participants counted the occurrence times of the rare fine or rare coarse checkerboards in different experimental conditions. We focused on early visual ERP differences as a function of checkerboard size and the classical P3b ERP component as an indicator of cognitive processing. RESULTS: We found an early (100-200 ms after stimulus onset occipital ERP effect of checkerboard size (dominant spatial frequency. This effect was weaker in the Asperger than in the control observers. Further a typical parietal/central oddball-P3b occurred at 500 ms with the rare checkerboards. The P3b showed a right-hemispheric lateralization, which was more prominent in Asperger than in control observers. DISCUSSION: The difference in the early occipital ERP effect between the two groups may be a physiological marker of differences in the processing of small visual details in Asperger observers compared to normal controls. The stronger lateralization of the P3b in Asperger observers may indicate a stronger involvement of the right-hemispheric network of bottom-up attention. The lateralization of the P3b signal might be a compensatory consequence of the compromised early checksize effect. Higher-level analytical information processing units may need to compensate for difficulties in low-level signal analysis.

  9. Altered patterns of heartbeat-evoked potentials in depersonalization/derealization disorder: neurophysiological evidence for impaired cortical representation of bodily signals.

    Science.gov (United States)

    Schulz, André; Köster, Susann; Beutel, Manfred E; Schächinger, Hartmut; Vögele, Claus; Rost, Silke; Rauh, Manfred; Michal, Matthias

    2015-06-01

    Core features of depersonalization/derealization disorder (DPD) are emotional numbing and feelings of disembodiment. Although there are several neurophysiological findings supporting subjective emotional numbing, the psychobiology of disembodiment remains unclear. Heartbeat-evoked potentials (HEPs), which are considered psychophysiological indicators for the cortical representation of afferent signals originating from the cardiovascular system, were assessed in 23 patients with DPD and 24 healthy control individuals during rest and while performing a heartbeat perception task. Absolute HEP amplitudes did not differ between groups. Nevertheless, healthy individuals showed higher HEPs during the heartbeat perception task than during rest, whereas no such effect was found in patients with DPD (p = .031). Patients with DPD had higher total levels of salivary α-amylase than did healthy individuals (9626.6 [8200.0] versus 5344.3 [3745.8] kU min/l; p = .029), but there were no group differences in cardiovascular measures (heart rate = 76.2 [10.1] versus 74.3 [7.5] beats/min, p = .60; normalized low-frequency heart rate variability = 0.63 [0.15] versus 0.56 [0.15] normalized units, p = .099; low frequency/high frequency ratio = 249.3 [242.7] versus 164.8 [108.8], p = .10), salivary cortisol (57.5 [46.7] versus 55.1 [43.6] nmol min/l, p = .86), or cortisone levels (593.2 [260.3] versus 543.8 [257.1] nmol min/l, p = .52). These results suggest altered cortical representation of afferent signals originating from the cardiovascular system in patients with DPD, which may be associated with higher sympathetic tone. These findings may reflect difficulties of patients with DPD to attend to their actual bodily experiences.

  10. Effect of xenon on excitatory and inhibitory transmission in rat spinal ventral horn neurons.

    Science.gov (United States)

    Yamamoto, Tomohiro; Honda, Hiroyuki; Baba, Hiroshi; Kohno, Tatsuro

    2012-05-01

    The minimum alveolar concentration is determined in the spinal cord rather than in the brain. Xenon inhibits glutamatergic excitatory synaptic transmission in the dorsal horn neurons. However, its actions in the ventral horn neurons have not been investigated. The effects of 50 or 75% xenon on excitatory and inhibitory synaptic transmission were examined in the spinal lamina IX neurons of neonatal rats by using a whole cell patch clamp technique. Fifty percent xenon inhibited the α-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid-induced currents (amplitudes = 72 ± 9% and integrated area = 73 ± 13% of the control values), and α-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid receptor-mediated electrically evoked excitatory postsynaptic currents (amplitudes = 69 ± 13% of the control values). Seventy-five percent xenon similarly inhibited α-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid-induced currents. However, xenon had no effect on the N-methyl-D-aspartate-induced currents or N-methyl-D-aspartate receptor-mediated electrically evoked excitatory postsynaptic currents. Xenon decreased the amplitude, but not the frequency, of miniature excitatory postsynaptic currents. There were no discernible effects on the currents induced by γ-aminobutyric acid or glycine or on miniature inhibitory postsynaptic currents. Xenon inhibits α-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid receptor-mediated glutamatergic excitatory transmission in the spinal lamina IX neurons via a postsynaptic mechanism. In contrast, there are no substantial effects on N-methyl-D-aspartate receptor-mediated or inhibitory synaptic transmission. The suppressive effects on excitatory synaptic transmission in the ventral horn neurons partly account for the mechanism behind xenon's ability to produce immobility in response to noxious stimuli and to determine the minimum alveolar concentration.

  11. Xenon inhibits excitatory but not inhibitory transmission in rat spinal cord dorsal horn neurons

    Science.gov (United States)

    2010-01-01

    Background The molecular targets for the promising gaseous anaesthetic xenon are still under investigation. Most studies identify N-methyl-D-aspartate (NMDA) receptors as the primary molecular target for xenon, but the role of α-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid (AMPA) receptors is less clear. In this study we evaluated the effect of xenon on excitatory and inhibitory synaptic transmission in the superficial dorsal horn of the spinal cord using in vitro patch-clamp recordings from rat spinal cord slices. We further evaluated the effects of xenon on innocuous and noxious stimuli using in vivo patch-clamp method. Results In vitro, xenon decreased the amplitude and area under the curve of currents induced by exogenous NMDA and AMPA and inhibited dorsal root stimulation-evoked excitatory postsynaptic currents. Xenon decreased the amplitude, but not the frequency, of miniature excitatory postsynaptic currents. There was no discernible effect on miniature or evoked inhibitory postsynaptic currents or on the current induced by inhibitory neurotransmitters. In vivo, xenon inhibited responses to tactile and painful stimuli even in the presence of NMDA receptor antagonist. Conclusions Xenon inhibits glutamatergic excitatory transmission in the superficial dorsal horn via a postsynaptic mechanism. There is no substantial effect on inhibitory synaptic transmission at the concentration we used. The blunting of excitation in the dorsal horn lamina II neurons could underlie the analgesic effect of xenon. PMID:20444263

  12. Intraurethral stimulation evokes bladder responses via 2 distinct reflex pathways.

    Science.gov (United States)

    Woock, John P; Yoo, Paul B; Grill, Warren M

    2009-07-01

    Recent animal studies have shown that selective activation of pudendal nerve branches can evoke bladder responses through 2 distinct reflex pathways. We examined intraurethral electrical stimulation as a minimally invasive means of selectively activating these pathways in the cat. Bladder responses evoked by intraurethral electrical stimulation were measured in alpha-chloralose anesthetized male cats at different stimulation frequencies, stimulation intensities and intraurethral locations. Intraurethral electrical stimulation evoked inhibitory and excitatory bladder reflexes depending on stimulation frequency and location. Stimulation in the penile urethra 0 to 3 cm from the urethral meatus at 33 Hz evoked bladder contraction and at 10 Hz it evoked bladder relaxation. These responses were abolished after bilateral transection of the dorsal penile nerves. Stimulation in the membranous urethra 5 to 7 cm from the urethral meatus at 2, 10 and 33 Hz evoked bladder contractions. These responses were abolished after bilateral transection of the cranial sensory nerves. Following acute spinal cord transection bladder contractions were still evoked by 33 Hz stimulation in the penile urethra but not by stimulation at any frequency in the membranous urethra. Intraurethral electrical stimulation selectively evoked bladder responses by activating 2 distinct pudendal afferent pathways. Responses depended on stimulation frequency and location. Intraurethral electrical stimulation is a valid means of determining the pathways involved in bladder responses evoked by pudendal nerve stimulation.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Axonal dynamics of excitatory and inhibitory neurons in somatosensory cortex.

    Directory of Open Access Journals (Sweden)

    Sally A Marik

    2010-06-01

    Full Text Available Cortical topography can be remapped as a consequence of sensory deprivation, suggesting that cortical circuits are continually modified by experience. To see the effect of altered sensory experience on specific components of cortical circuits, we imaged neurons, labeled with a genetically modified adeno-associated virus, in the intact mouse somatosensory cortex before and after whisker plucking. Following whisker plucking we observed massive and rapid reorganization of the axons of both excitatory and inhibitory neurons, accompanied by a transient increase in bouton density. For horizontally projecting axons of excitatory neurons there was a net increase in axonal projections from the non-deprived whisker barrel columns into the deprived barrel columns. The axon collaterals of inhibitory neurons located in the deprived whisker barrel columns retracted in the vicinity of their somata and sprouted long-range projections beyond their normal reach towards the non-deprived whisker barrel columns. These results suggest that alterations in the balance of excitation and inhibition in deprived and non-deprived barrel columns underlie the topographic remapping associated with sensory deprivation.

  15. Regionally selective alterations in local cerebral glucose utilization evoked by charybdotoxin, a blocker of central voltage-activated K+-channels.

    Science.gov (United States)

    Cochran, S M; Harvey, A L; Pratt, J A

    2001-11-01

    The quantitative [14C]-2-deoxyglucose autoradiographic technique was employed to investigate the effect of charybdotoxin, a blocker of certain voltage-activated K+ channels, on functional activity, as reflected by changes in local rates of cerebral glucose utilization in rat brain. Intracerebroventricular administration of charybdotoxin, at doses below those producing seizure activity, produced a heterogeneous effect on glucose utilization throughout the brain. Out of the 75 brain regions investigated, 24 displayed alterations in glucose utilization. The majority of these changes were observed with the intermediate dose of charybdotoxin administered (12.5 pmol), with the lower (6.25 pmol) and higher (25 pmol) doses of charybdotoxin producing a much more restricted pattern of change in glucose utilization. In brain regions which displayed alterations in glucose at all doses of charybdotoxin administered, no dose dependency in terms of the magnitude of change was observed. The 21 brain regions which displayed altered functional activity after administration of 12.5 pmol charybdotoxin were predominantly limited to the hippocampus, limbic and motor structures. In particular, glucose utilization was altered within three pathways implicated within learning and memory processes, the septohippocampal pathway, Schaffer collaterals within the hippocampus and the Papez circuit. The nigrostriatal pathway also displayed altered local cerebral glucose utilization. These data indicate that charybdotoxin produces alterations in functional activity within selected pathways in the brain. Furthermore the results raise the possibility that manipulation of particular subtypes of Kv1 channels in the hippocampus and related structures may be a means of altering cognitive processes without causing global changes in neural activity throughout the brain.

  16. Firing clamp: A novel method for single-trial estimation of excitatory and inhibitory synaptic neuronal conductances

    Directory of Open Access Journals (Sweden)

    Anton eChizhov

    2014-03-01

    Full Text Available Understanding non-stationary neuronal activity as seen in vivo requires estimation of both excitatory and inhibitory synaptic conductances from a single trial of recording. We propose a new intracellular recording method for this purpose called firing clamp. Synaptic conductances are estimated from the characteristics of artificially evoked probe spikes, namely the spike amplitude and the mean subthreshold potential, which are sensitive to both excitatory and inhibitory synaptic input signals. The probe spikes, timed at a fixed rate, are evoked in the dynamic-clamp mode by injected meander-like current steps, with the step duration depending on neuronal membrane voltage. We test the method with perforated-patch recordings from isolated cells stimulated by external application or synaptic release of transmitter, and validate the method with simulations of a biophysically-detailed neuron model. The results are compared with the conductance estimates based on conventional current-clamp recordings.

  17. Differential effects of tetanus toxin on inhibitory and excitatory synaptic transmission in mammalian spinal cord neurons in culture: a presynaptic locus of action for tetanus toxin.

    Science.gov (United States)

    Bergey, G K; Bigalke, H; Nelson, P G

    1987-01-01

    Tetanus toxin reduces monosynaptic inhibitory and excitatory synaptic transmission in mouse spinal cord neurons in culture. Inhibitory transmission is preferentially reduced by the toxin; however, excitatory transmission is also ultimately reduced and blocked by the concentrations of toxin used in these studies. Recordings from monosynaptically connected cell pairs revealed a marked diminution in amplitude of evoked monosynaptic inhibitory postsynaptic potentials coincident with the onset of convulsant action at a time when evoked monosynaptic EPSPs were relatively unaffected. Increased polysynaptic excitation occurred as a result of diminished inhibition. This supports the reduction of inhibition as an important mechanism in the convulsant action of tetanus toxin. Quantal analysis of the late effects of tetanus toxin on the monosynaptic excitatory postsynaptic potential revealed a reduction in quantal number with no reduction in quantal size, thus demonstrating a presynaptic locus of action for the toxin on spinal neurons.

  18. Perinatal sulfur dioxide exposure alters brainstem parasympathetic control of heart rate.

    Science.gov (United States)

    Woerman, Amanda L; Mendelowitz, David

    2013-07-01

    Sulfur dioxide (SO₂) is an air pollutant that impedes neonatal development and induces adverse cardiorespiratory health effects, including tachycardia. Here, an animal model was developed that enabled characterization of (i) in vivo alterations in heart rate and (ii) altered activity in brainstem neurons that control heart rate after perinatal SO₂ exposure. Pregnant Sprague-Dawley dams and their pups were exposed to 5 parts per million SO₂ for 1 h daily throughout gestation and 6 days postnatal. Electrocardiograms were recorded from pups at 5 days postnatal to examine changes in basal and diving reflex-evoked changes in heart rate following perinatal SO₂ exposure. In vitro studies employed whole-cell patch-clamp electrophysiology to examine changes in neurotransmission to cardiac vagal neurons within the nucleus ambiguus upon SO₂ exposure using a preparation that maintains fictive inspiratory activity recorded from the hypoglossal rootlet. Perinatal SO₂ exposure increased heart rate and blunted the parasympathetic-mediated diving reflex-evoked changes in heart rate. Neither spontaneous nor inspiratory-related inhibitory GABAergic or glycinergic neurotransmission to cardiac vagal neurons was altered by SO₂ exposure. However, excitatory glutamatergic neurotransmission was decreased by 51.2% upon SO₂ exposure. This diminished excitatory neurotransmission was tetrodotoxin-sensitive, indicating SO₂ exposure impaired the activity of preceding glutamatergic neurons that synapse upon cardiac vagal neurons. Diminished glutamatergic, but unaltered inhibitory neurotransmission to cardiac vagal neurons provides a mechanism for the observed SO₂-induced elevated heart rate via an impairment of brainstem cardioinhibitory parasympathetic activity to the heart.

  19. Motor cortex broadly engages excitatory and inhibitory neurons in somatosensory barrel cortex.

    Science.gov (United States)

    Kinnischtzke, Amanda K; Simons, Daniel J; Fanselow, Erika E

    2014-08-01

    Anatomical studies have shown that primary somatosensory (S1) and primary motor (M1) cortices are reciprocally connected. The M1 to S1 projection is thought to represent a modulatory signal that conveys motor-related information to S1. Here, we investigated M1 synaptic inputs to S1 by injecting an AAV virus containing channelrhodopsin-2 and a fluorescent tag into M1. Consistent with previous results, we found labeling of M1 axons within S1 that was most robust in the deep layers and in L1. Labeling was sparse in L4 and was concentrated in the interbarrel septa, largely avoiding barrel centers. In S1, we recorded in vitro from regular-spiking excitatory neurons and fast-spiking and somatostatin-expressing inhibitory interneurons. All 3 cell types had a high probability of receiving direct excitatory M1 input. Both excitatory and inhibitory cells within L4 were the least likely to receive such input from M1. Disynaptic inhibition was observed frequently, indicating that M1 recruits substantial inhibition within S1. Additionally, a subpopulation of L6 regular-spiking excitatory neurons received exceptionally strong M1 input. Overall, our results suggest that activation of M1 evokes within S1 a bombardment of excitatory and inhibitory synaptic activity that could contribute in a layer-specific manner to state-dependent changes in S1. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  20. Amphetamine modulates excitatory neurotransmission through endocytosis of the glutamate transporter EAAT3 in dopamine neurons.

    Science.gov (United States)

    Underhill, Suzanne M; Wheeler, David S; Li, Minghua; Watts, Spencer D; Ingram, Susan L; Amara, Susan G

    2014-07-16

    Amphetamines modify the brain and alter behavior through mechanisms generally attributed to their ability to regulate extracellular dopamine concentrations. However, the actions of amphetamine are also linked to adaptations in glutamatergic signaling. We report here that when amphetamine enters dopamine neurons through the dopamine transporter, it stimulates endocytosis of an excitatory amino acid transporter, EAAT3, in dopamine neurons. Consistent with this decrease in surface EAAT3, amphetamine potentiates excitatory synaptic responses in dopamine neurons. We also show that the process of internalization is dynamin- and Rho-mediated and requires a unique sequence in the cytosolic C terminus of EAAT3. Introduction of a peptide based on this motif into dopamine neurons blocks the effects of amphetamine on EAAT3 internalization and its action on excitatory responses. These data indicate that the internalization of EAAT3 triggered by amphetamine increases glutamatergic signaling and thus contributes to the effects of amphetamine on neurotransmission. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Excitatory neurotransmitters in the tentacle flexor muscles responsible for space positioning of the snail olfactory organ.

    Science.gov (United States)

    Krajcs, N; Hernádi, L; Elekes, K; Kimura, S; Kiss, T

    2014-03-01

    Recently, three novel flexor muscles (M1, M2 and M3) in the posterior tentacles of the snail have been described, which are responsible for the patterned movements of the tentacles of the snail, Helix pomatia. In this study, we have demonstrated that the muscles received a complex innervation pattern via the peritentacular and olfactory nerves originating from different clusters of motoneurons of the cerebral ganglia. The innervating axons displayed a number of varicosities and established neuromuscular contacts of different ultrastructural forms. Contractions evoked by nerve stimulation could be mimicked by external acetylcholine (ACh) and glutamate (Glu), suggesting that ACh and Glu are excitatory transmitters at the neuromuscular contacts. Choline acetyltransferase and vesicular glutamate transporter immunolabeled axons innervating flexor muscles were demonstrated by immunohistochemistry and in Western blot experiments. Nerve- and transmitter-evoked contractions were similarly attenuated by cholinergic and glutamatergic antagonists supporting the dual excitatory innervation. Dopamine (DA, 10⁻⁵ M) oppositely modulated thin (M1/M2) and thick (M3) muscle responses evoked by stimulation of the olfactory nerve, decreasing the contractions of the M1/M2 and increasing those of M3. In both cases, the modulation site was presynaptic. Serotonin (5-HT) at high concentration (10⁻⁵ M) increased the amplitude of both the nerve- and the ACh-evoked contractions in all muscles. The relaxation rate was facilitated suggesting pre- and postsynaptic site of action. Our data provided evidence for a DAergic and 5-HTergic modulation of cholinergic nerves innervating flexor muscles of the tentacles as well as the muscles itself. These effects of DA and 5-HT may contribute to the regulation of sophisticated movements of tentacle muscles lacking inhibitory innervation.

  2. Neuropathic pain-induced enhancement of spontaneous and pain-evoked neuronal activity in the periaqueductal gray that is attenuated by gabapentin.

    Science.gov (United States)

    Samineni, Vijay K; Premkumar, Louis S; Faingold, Carl L

    2017-07-01

    Neuropathic pain is a debilitating pathological condition that is poorly understood. Recent evidence suggests that abnormal central processing occurs during the development of neuropathic pain induced by the cancer chemotherapeutic agent, paclitaxel. Yet, it is unclear what role neurons in supraspinal pain network sites, such as the periaqueductal gray, play in altered behavioral sensitivity seen during chronic pain conditions. To elucidate these mechanisms, we studied the spontaneous and thermally evoked firing patterns of ventrolateral periaqueductal gray (vlPAG) neurons in awake-behaving rats treated with paclitaxel to induce neuropathic pain. In the present study, vlPAG neurons in naive rats exhibited either excitatory, inhibitory, or neutral responses to noxious thermal stimuli, as previously observed. However, after development of behavioral hypersensitivity induced by the chemotherapeutic agent, paclitaxel, vlPAG neurons displayed increased neuronal activity and changes in thermal pain-evoked neuronal activity. This involved elevated levels of spontaneous firing and heightened responsiveness to nonnoxious stimuli (allodynia) as well as noxious thermal stimuli (hyperalgesia) as compared with controls. Furthermore, after paclitaxel treatment, only excitatory neuronal responses were observed for both nonnoxious and noxious thermal stimuli. Systemic administration of gabapentin, a nonopioid analgesic, induced significant dose-dependent decreases in the elevated spontaneous and thermally evoked vlPAG neuronal firing to both nonnoxious and noxious thermal stimuli in rats exhibiting neuropathic pain, but not in naive rats. Thus, these results show a strong correlation between behavioral hypersensitivity to thermal stimuli and increased firing of vlPAG neurons in allodynia and hyperalgesia that occur in this neuropathic pain model.

  3. Alterações dos potenciais evocados auditivos do tronco encefálico em pacientes com esclerose múltipla Alterations in early auditory evoked potentials in multiple sclerosis patients

    Directory of Open Access Journals (Sweden)

    Tania Mara Assis Lima

    2009-04-01

    Full Text Available A presença de alterações nos potenciais evocados auditivos do tronco encefálico (PEATE em indivíduos com doenças desmielinizantes sugere lesão do tronco encefálico. OBJETIVOS: O objetivo do presente estudo foi avaliar a incidência de alterações auditivas e dos PEATE em indivíduos com esclerose múltipla (EM. MATERIAL E MÉTODO: Participaram do estudo 16 pacientes do sexo feminino e 9 do sexo masculino com diagnóstico definido de EM. Testes audiométricos e pesquisa dos PEATE foram realizados em todos os indivíduos. Para a classificação dos PEATE utilizou-se a classificação proposta por Jerger (1986 na análise da morfologia das ondas. FORMA DE ESTUDO: Estudo de coorte contemporânea com corte transversal. RESULTADOS: Dos 50 PEATE realizados, 70% foram classificados como tipo I (resposta normal pela classificação de Jerger. Considerando-se como alterados os PEATE dos tipos II, III, IV ou V da classificação de Jerger em pelo menos um dos lados, encontrou-se 31,25% de alterações no sexo feminino e 44,44% no masculino, totalizando 36%. CONCLUSÕES: Estes achados enfatizam a relevância do estudo dos PEATE em casos de suspeita clínica de doenças desmielinizantes e naqueles com diagnóstico definido de EM.Alterations in early auditory evoked potentials (EAEP in individuals with demyelinating disease are suggestive of lesions in the brainstem. AIM: this study aims to evaluate the prevalence of hearing disorders and altered EAEP in multiple sclerosis (MS patients. MATERIALS AND METHOD: sixteen female and nine male patients with a defined diagnosis of multiple sclerosis took part in this study. All individuals underwent hearing and EAEP tests. The wave forms were categorized according to Jerger (1986. RESULTS: fifty EAEP tests were carried out; 70% were classified as type I (normal response according to Jerger's criteria. Altered EAEP results in at least one ear were classified into types II, III, IV or V according to Jerger

  4. Novel functions for ADF/cofilin in excitatory synapses - lessons from gene-targeted mice.

    Science.gov (United States)

    Rust, Marco B

    2015-01-01

    Actin filaments (F-actin) are the major structural component of excitatory synapses. In excitatory synapses, F-actin is enriched in presynaptic terminals and in postsynaptic dendritic spines, and actin dynamics - the spatiotemporally controlled assembly and disassembly of F-actin - have been implicated in pre- and postsynaptic physiology, additionally to their function in synapse morphology. Hence, actin binding proteins that control actin dynamics have moved into the focus as regulators of synapse morphology and physiology. Actin depolymerizing proteins of the ADF/cofilin family are important regulators of actin dynamics, and several recent studies highlighted the relevance of cofilin 1 for dendritic spine morphology, trafficking of postsynaptic glutamate receptors, and synaptic plasticity. Conversely, almost nothing was known about the synaptic function of ADF, a second ADF/cofilin family member present at excitatory synapses, and it remained unknown whether ADF/cofilin is relevant for presynaptic physiology. To comprehensively characterize the synaptic function of ADF/cofilin we made use of mutant mice lacking either ADF or cofilin 1 or both proteins. Our analysis revealed presynaptic defects (altered distribution and enhanced exocytosis of synaptic vesicles) and behavioral abnormalities reminiscent of attention deficit-hyperactivity disorder in double mutants that were not present in single mutants. Hence, by exploiting gene-targeted mice, we demonstrated the relevance of ADF for excitatory synapses, and we unraveled novel functions for ADF/cofilin in presynaptic physiology and behavior.

  5. Evoked cavernous activity.

    Science.gov (United States)

    Yilmaz, Uğur; Soylu, Ahmet; Ozcan, Cemal; Kutlu, Ramazan; Güneş, Ali

    2002-01-01

    Corpus cavernosum electromyography has been widely done to evaluate autonomic dysfunction in patients with erectile dysfunction. We assessed the value of corpus cavernosum electromyography, evoked cavernous activity and penile sympathetic skin responses for their accuracy in determining autonomic involvement in cases of erectile dysfunction. We evaluated 75 men with erectile dysfunction by corpus cavernosum electromyography, evoked cavernous activity and penile sympathetic skin response tests at our neurourology laboratory. The etiology of dysfunction was vascular, neurogenic, psychogenic or mixed based on a detailed medical and sexual history, physical examination, electrophysiological and laboratory studies, penile color Doppler ultrasonography, and cavernosography and/or cavernosometry. Autonomic involvement was clinically assessed by systemic findings, such as orthostatic hypotension, impaired gastrointestinal motility, sinus dysrhythmia and secretomotor changes. A concentric electromyography needle placed in the right cavernous body was used to record corpus cavernosum electromyography and evoked cavernous activity. The right median nerve was stimulated electrically with 13 to 16 mA. to determine evoked cavernous activity and the penile sympathetic skin response. The latter response was recorded with silver disc electrodes placed on the left cavernous body. All tests were performed using an electromyography/evoked potential machine. We determined the relationships among corpus cavernosum electromyography, evoked cavernous activity and penile sympathetic skin response tests in respect to etiological factors. The 56 patients with normal corpus cavernosum electromyography activity had also evoked cavernous activity and a penile sympathetic skin response except for 1 with no penile sympathetic skin response but evoked cavernous activity. None of these patients had autonomic neuropathy. Of the 19 patients without corpus cavernosum electromyography activity 11 had

  6. Amiodarone reduces depolarization-evoked glutamate release from hippocampual synaptosomes

    Directory of Open Access Journals (Sweden)

    Chia Yu Chang

    2017-03-01

    Full Text Available Decreased brain glutamate level has emerged as a new therapeutic approach for epilepsy. This study investigated the effect and mechanism of amiodarone, an anti-arrhythmic drug with antiepileptic activity, on glutamate release in the rat hippocampus. In a synaptosomal preparation, amiodarone reduced 4-aminopyridine-evoked Ca2+-dependent glutamate release and cytosolic Ca2+ concentration elevation. Amiodarone did not affect the 4-aminopyridine-evoked depolarization of the synaptosomal membrane potential or the Na+ channel activator veratridine-evoked glutamate release, indicating that the amiodarone-mediated inhibition of glutamate release is not caused by a decrease in synaptosomal excitability. The inhibitory effect of amiodarone on 4-aminopyridine-evoked glutamate release was markedly decreased in synaptosomes pretreated with the Cav2.2 (N-type and Cav2.1 (P/Q-type channel blocker ω-conotoxin MVIIC, the calmodulin antagonists W7 and calmidazolium, or the protein kinase A inhibitors H89 and KT5720. However, the intracellular Ca2+-release inhibitors dantrolene and CGP37157 had no effect on the amiodarone-mediated inhibition of glutamate release. Furthermore, amiodarone reduced the frequency of miniature excitatory postsynaptic currents without affecting their amplitude in hippocampal slices. Our data suggest that amiodarone reduces Ca2+ influx through N- and P/Q-type Ca2+ channels, subsequently reducing the Ca2+-calmodulin/protein kinase A cascade to inhibit the evoked glutamate release from rat hippocampal nerve terminals.

  7. SynDIG1 promotes excitatory synaptogenesis independent of AMPA receptor trafficking and biophysical regulation.

    Directory of Open Access Journals (Sweden)

    Kathryn L Lovero

    Full Text Available AMPA receptors-mediators of fast, excitatory transmission and synaptic plasticity in the brain-achieve great functional diversity through interaction with different auxiliary subunits, which alter both the trafficking and biophysical properties of these receptors. In the past several years an abundance of new AMPA receptor auxiliary subunits have been identified, adding astounding variety to the proteins known to directly bind and modulate AMPA receptors. SynDIG1 was recently identified as a novel AMPA receptor interacting protein that directly binds to the AMPA receptor subunit GluA2 in heterologous cells. Functionally, SynDIG1 was found to regulate the strength and density of AMPA receptor containing synapses in hippocampal neurons, though the way in which SynDIG1 exerts these effects remains unknown. Here, we aimed to determine if SynDIG1 acts as a traditional auxiliary subunit, directly regulating the function and localization of AMPA receptors in the rat hippocampus. We find that, unlike any of the previously characterized AMPA receptor auxiliary subunits, SynDIG1 expression does not impact AMPA receptor gating, pharmacology, or surface trafficking. Rather, we show that SynDIG1 regulates the number of functional excitatory synapses, altering both AMPA and NMDA receptor mediated transmission. Our findings suggest that SynDIG1 is not a typical auxiliary subunit to AMPA receptors, but instead is a protein critical to excitatory synaptogenesis.

  8. 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...... contralateral to stimulus side and additionally an unexpected 20 Hz activity was observed slightly lateralized in the frontal central region. The gamma phase locking may be a manifestation of early somatosensory feature integration. The analyses suggest that the high frequency activity consists of two distinct...

  9. N-cadherin regulates molecular organization of excitatory and inhibitory synaptic circuits in adult hippocampus in vivo.

    Science.gov (United States)

    Nikitczuk, Jessica S; Patil, Shekhar B; Matikainen-Ankney, Bridget A; Scarpa, Joseph; Shapiro, Matthew L; Benson, Deanna L; Huntley, George W

    2014-08-01

    N-Cadherin and β-catenin form a transsynaptic adhesion complex required for spine and synapse development. In adulthood, N-cadherin mediates persistent synaptic plasticity, but whether the role of N-cadherin at mature synapses is similar to that at developing synapses is unclear. To address this, we conditionally ablated N-cadherin from excitatory forebrain synapses in mice starting in late postnatal life and examined hippocampal structure and function in adulthood. In the absence of N-cadherin, β-catenin levels were reduced, but numbers of excitatory synapses were unchanged, and there was no impact on number or shape of dendrites or spines. However, the composition of synaptic molecules was altered. Levels of GluA1 and its scaffolding protein PSD95 were diminished and the density of immunolabeled puncta was decreased, without effects on other glutamate receptors and their scaffolding proteins. Additionally, loss of N-cadherin at excitatory synapses triggered increases in the density of markers for inhibitory synapses and decreased severity of hippocampal seizures. Finally, adult mutant mice were profoundly impaired in hippocampal-dependent memory for spatial episodes. These results demonstrate a novel function for the N-cadherin/β-catenin complex in regulating ionotropic receptor composition of excitatory synapses, an appropriate balance of excitatory and inhibitory synaptic proteins and the maintenance of neural circuitry necessary to generate flexible yet persistent cognitive and synaptic function. © 2014 Wiley Periodicals, Inc.

  10. 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 releasing gliotransmitters, which in turn modulate synaptic transmission. Here we investigated if astrocytes present in the ventral horn of the spinal cord modulate synaptic transmission. We evoked synaptic inputs in ventral horn neurons recorded in a slice preparation from the spinal cord of neonatal mice...... an inhibition occurring at the presynaptic side of synapses. In the presence of blockers for extracellular ectonucleotidases, TFLLR did not induce presynaptic inhibition. Puffing adenosine reproduced the effect of TFLLR and blocking adenosine A1 receptors with 8-Cyclopentyl-1,3-dipropylxanthine prevented it....... Altogether our results show that ventral horn astrocytes are responsible for a tonic and a phasic inhibition of excitatory synaptic transmission by releasing ATP, which gets converted into adenosine that binds to inhibitory presynaptic A1 receptors....

  11. 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...

  12. Proprioceptive evoked gamma oscillations

    DEFF Research Database (Denmark)

    Arnfred, Sidse M; Hansen, Lars Kai; Parnas, Josef

    2007-01-01

    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...

  13. Excitatory and inhibitory actions of isoprostanes in human and canine airway smooth muscle.

    Science.gov (United States)

    Janssen, L J; Premji, M; Netherton, S; Catalli, A; Cox, G; Keshavjee, S; Crankshaw, D J

    2000-11-01

    Isoprostanes are generated nonenzymatically during free radical-mediated lipid peroxidation, and are used clinically and experimentally as markers of oxidative stress. However, their biological effects are poorly understood. We examined the effects of seven different 8-isoprostanes in human and canine airway smooth muscles. In large order airways (carina) of the human, several isoprostanes evoked powerful contractions, with 8-iso-prostaglandin (PG) E(2), 8-iso-PGF(1 alpha), and 8-iso-PGF(2 alpha) being the most efficacious (and with logEC(50) values of 7.0, 5.9, and 6.2 microM, respectively). These contractions were sensitive to the prostanoid TP receptor antagonist ICI 192,605 (0.1-1 microM), but not the EP prostanoid receptor antagonist AH-6809 (50 microM), or the leukotriene receptor antagonists monteleukast or ICI 198,615 (both 1 microM). Qualitatively similar results were obtained in small order human airways (<2 mm o.d.), except that the isoprostanes were generally slightly less potent. None of the isoprostanes had any marked excitatory effect in canine airways. In carbachol-preconstricted tissues (pretreated with ICI 192,605 to block any potential contraction), several isoprostanes completely relaxed canine airways: 8-iso-PGE(1), 8-iso-PGE(2), and 8-iso-PGF(3 alpha) were the most potent, with logIC(50) values of 6.9, 6.9, and 5.7, respectively. Only 8-iso-PGF(3 alpha) relaxed human airways (logIC(50) = 4.9). Our results show that several 8-isoprostanes are highly biologically active in human and canine airways, evoking both excitatory and/or inhibitory effects, and that these effects are compound, species, and tissue dependent.

  14. Rapid plasticity at inhibitory and excitatory synapses in the hippocampus induced by ictal epileptiform discharges.

    Science.gov (United States)

    Lopantsev, Valeri; Both, Martin; Draguhn, Andreas

    2009-03-01

    Epileptic seizures can induce pathological processes of plasticity in the brain that tend to promote the generation of further seizures. However, the immediate impact of epileptic seizures on cellular excitability remains poorly understood. In order to unravel such early mechanisms of epilepsy-induced plasticity, we studied synaptic transmission before and shortly after three ictal discharges induced by transient elevation of extracellular K(+) in mouse hippocampal slices. Discharges were initiated in the CA3 region and propagated via the Schaffer collaterals into CA1 where they were associated with sustained membrane depolarization and bursts of action potentials in CA1 pyramidal cells. Subsequently, discharges were followed by long-term potentiation (LTP) of Schaffer collateral-evoked field excitatory post-synaptic potentials (EPSPs) in the CA1. The ability to generate epileptiform activity in response to repetitive stimulation was enhanced during LTP. Changes in both inhibitory and excitatory synaptic transmission contributed to LTP in CA1 pyramidal cells. Discharges reduced gamma-aminobutyric acid-A receptor-mediated hyperpolarizing inhibitory post-synaptic potentials by shifting their reversal potentials in a positive direction. At the same time, the amplitudes of Schaffer collateral-evoked RS-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated EPSPs and action potential-independent miniature EPSPs were enhanced. However, N-methyl-d-aspartate receptor-mediated EPSPs remained unchanged. Paired-pulse stimulation revealed a reduced probability of glutamate release. Together, these changes in synaptic transmission produce a sustained increase in hippocampal excitability. We conclude that a few seizure-like ictal episodes are sufficient to cause fast and lasting changes in the excitation/inhibition balance in hippocampal networks, and therefore may contribute to early phases of progressive epileptogenesis.

  15. Cerebellar Shank2 Regulates Excitatory Synapse Density, Motor Coordination, and Specific Repetitive and Anxiety-Like Behaviors.

    Science.gov (United States)

    Ha, Seungmin; Lee, Dongwon; Cho, Yi Sul; Chung, Changuk; Yoo, Ye-Eun; Kim, Jihye; Lee, Jiseok; Kim, Woohyun; Kim, Hyosang; Bae, Yong Chul; Tanaka-Yamamoto, Keiko; Kim, Eunjoon

    2016-11-30

    Shank2 is a multidomain scaffolding protein implicated in the structural and functional coordination of multiprotein complexes at excitatory postsynaptic sites as well as in psychiatric disorders, including autism spectrum disorders. While Shank2 is strongly expressed in the cerebellum, whether Shank2 regulates cerebellar excitatory synapses, or contributes to the behavioral abnormalities observed in Shank2-/- mice, remains unexplored. Here we show that Shank2-/- mice show reduced excitatory synapse density in cerebellar Purkinje cells in association with reduced levels of excitatory postsynaptic proteins, including GluD2 and PSD-93, and impaired motor coordination in the Erasmus test. Shank2 deletion restricted to Purkinje cells (Pcp2-Cre;Shank2fl/fl mice) leads to similar reductions in excitatory synapse density, synaptic protein levels, and motor coordination. Pcp2-Cre;Shank2fl/fl mice do not recapitulate autistic-like behaviors observed in Shank2-/- mice, such as social interaction deficits, altered ultrasonic vocalizations, repetitive behaviors, and hyperactivity. However, Pcp2-Cre;Shank2fl/fl mice display enhanced repetitive behavior in the hole-board test and anxiety-like behavior in the light-dark test, which are not observed in Shank2-/- mice. These results implicate Shank2 in the regulation of cerebellar excitatory synapse density, motor coordination, and specific repetitive and anxiety-like behaviors. The postsynaptic side of excitatory synapses contains multiprotein complexes, termed the postsynaptic density, which contains receptors, scaffolding/adaptor proteins, and signaling molecules. Shank2 is an excitatory postsynaptic scaffolding protein implicated in the formation and functional coordination of the postsynaptic density and has been linked to autism spectrum disorders. Using Shank2-null mice and Shank2-conditional knock-out mice with a gene deletion restricted to cerebellar Purkinje cells, we explored functions of Shank2 in the cerebellum. We

  16. BAER - brainstem auditory evoked response

    Science.gov (United States)

    ... auditory potentials; Brainstem auditory evoked potentials; Evoked response audiometry; Auditory brainstem response; ABR; BAEP ... Normal results vary. Results will depend on the person and the instruments used to perform the test.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Potentiation of excitatory transmission in substantia gelatinosa neurons of rat spinal cord by inhibition of estrogen receptor alpha

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    Li Kai-Cheng

    2010-12-01

    Full Text Available Abstract Background It has been shown that estrogen is synthesized in the spinal dorsal horn and plays a role in modulating pain transmission. One of the estrogen receptor (ER subtypes, estrogen receptor alpha (ERα, is expressed in the spinal laminae I-V, including substantia gelatinosa (SG, lamina II. However, it is unclear how ERs are involved in the modulation of nociceptive transmission. Results In the present study, a selective ERα antagonist, methyl-piperidino-pyrazole (MPP, was used to test the potential functional roles of spinal ERα in the nociceptive transmission. Using the whole-cell patch-clamp technique, we examined the effects of MPP on SG neurons in the dorsal root-attached spinal cord slice prepared from adult rats. We found that MPP increased glutamatergic excitatory postsynaptic currents (EPSCs evoked by the stimulation of either Aδ- or C-afferent fibers. Further studies showed that MPP treatment dose-dependently increased spontaneous EPSCs frequency in SG neurons, while not affecting the amplitude. In addition, the PKC was involved in the MPP-induced enhancement of synaptic transmission. Conclusions These results suggest that the selective ERα antagonist MPP pre-synaptically facilitates the excitatory synaptic transmission to SG neurons. The nociceptive transmission evoked by Aδ- and C-fiber stimulation could be potentiated by blocking ERα in the spinal neurons. Thus, the spinal estrogen may negatively regulate the nociceptive transmission through the activation of ERα.

  19. Theta-burst repetitive transcranial magnetic stimulation suppresses specific excitatory circuits in the human motor cortex.

    Science.gov (United States)

    Di Lazzaro, V; Pilato, F; Saturno, E; Oliviero, A; Dileone, M; Mazzone, P; Insola, A; Tonali, P A; Ranieri, F; Huang, Y Z; Rothwell, J C

    2005-06-15

    In four conscious patients who had electrodes implanted in the cervical epidural space for the control of pain, we recorded corticospinal volleys evoked by single-pulse transcranial magnetic stimulation (TMS) over the motor cortex before and after a 20 s period of continuous theta-burst stimulation (cTBS). It has previously been reported that this form of repetitive TMS reduces the amplitude of motor-evoked potentials (MEPs), with the maximum effect occurring at 5-10 min after the end of stimulation. The present results show that cTBS preferentially decreases the amplitude of the corticospinal I1 wave, with approximately the same time course. This is consistent with a cortical origin of the effect on the MEP. However, other protocols that lead to MEP suppression, such as short-interval intracortical inhibition, are characterized by reduced excitability of late I waves (particularly I3), suggesting that cTBS suppresses MEPs through different mechanisms, such as long-term depression in excitatory synaptic connections.

  20. Plasticity during motherhood: changes in excitatory and inhibitory layer 2/3 neurons in auditory cortex.

    Science.gov (United States)

    Cohen, Lior; Mizrahi, Adi

    2015-01-28

    Maternal behavior can be triggered by auditory and olfactory cues originating from the newborn. Here we report how the transition to motherhood affects excitatory and inhibitory neurons in layer 2/3 (L2/3) of the mouse primary auditory cortex. We used in vivo two-photon targeted cell-attached recording to compare the response properties of parvalbumin-expressing neurons (PVNs) and pyramidal glutamatergic neurons (PyrNs). The transition to motherhood shifts the average best frequency of PVNs to higher frequency by a full octave, with no significant effect on average best frequency of PyrNs. The presence of pup odors significantly reduced the spontaneous and evoked activity of PVN. This reduction of feedforward inhibition coincides with a complimentary increase in spontaneous and evoked activity of PyrNs. The selective shift of PVN frequency tuning should render pup odor-induced disinhibition more effective for high-frequency stimuli, such as ultrasonic vocalizations. Indeed, pup odors increased neuronal responses of PyrNs to pup ultrasonic vocalizations. We conclude that plasticity in the mothers is mediated, at least in part, via modulation of the feedforward inhibition circuitry in the auditory cortex. Copyright © 2015 the authors 0270-6474/15/351806-10$15.00/0.

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

    Directory of Open Access Journals (Sweden)

    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. Selecting and evoking innovators

    DEFF Research Database (Denmark)

    Kanstrup, Anne Marie; Christiansen, Ellen

    2006-01-01

    prepared for and conducted selection of and collaboration with innovators. The outcome was successful in the sense that the innovators produced excellent foundation for conceptual interaction design by creating mock-ups and explanations incarnating their preferences, attitudes and habits. By referring...... to theories of learning we try to explain how our way of working with selection and evoking of innovators has contributed to this positive result and how our approach to user-driven innovation can be regarded as a way to combine democracy and creativity in design....

  3. Evidence that luteinizing hormone suppression in response to inhibitory neuropeptides, beta-endorphin, interleukin-1 beta, and neuropeptide-K, may involve excitatory amino acids.

    Science.gov (United States)

    Bonavera, J J; Kalra, S P; Kalra, P S

    1993-07-01

    A large body of recent evidence suggests that a number of inhibitory and excitatory neuropeptides and amino acids may participate in the episodic secretion of hypothalamic LHRH and pituitary LH in castrated rats. However, the precise functional relationships among these messenger molecules in the control of LH secretion remain to be ascertained. The aim of this study was to test the hypothesis that inhibition of LH release by an opioid [beta-endorphin (beta END)], cytokine [interleukin-1 beta (IL-1 beta)], or tachykinin [neuropeptide-K (NPK)] is a result of diminished excitatory amino acid (EAA) signaling. Adult male rats were castrated and received an intracerebroventricular cannula in the third ventricle for administration of beta END (10 micrograms/rat), NPK (2.5 nmol/rat), or IL-1 beta (100 ng/rat) 2 weeks postcastration. One day before the experiments, rats received an intraatrial cannula for frequent blood sampling and for iv injection of the glutamate receptor agonist N-methyl-D-aspartate (NMDA; 5 mg/kg) at 30-min intervals. Blood samples for LH measurements were withdrawn immediately before and 10 min after each NMDA injection. The results show that intracerebroventricular beta END, IL-1 beta, or NPK inhibited LH release. Multiple injections of NMDA did not alter the existing pattern of LH secretion in castrated control rats. However, similar NMDA injections completely prevented the decrease in LH release by beta END, IL-1 beta, or NPK. Plasma LH levels in these rats remained within the range seen in untreated control rats throughout the 120-min duration of the experiment, and NMDA injections at 30-min intervals evoked pulses of LH that resembled those seen normally in castrated rats. The blockade of the inhibitory effects of the three peptides by NMDA and previous knowledge of hypothalamic sites of NMDA action suggest that EAA systems may represent a common pathway down-stream in the hypothalamic LHRH-regulating circuitry to mediate diminution of LH

  4. Selective modulation of excitatory and inhibitory microcircuits by dopamine

    Science.gov (United States)

    Gao, Wen-Jun; Goldman-Rakic, Patricia S.

    2003-03-01

    Dopamine plays an important role in the working memory functions of the prefrontal cortex, functions that are impacted in age-related memory decline, drug abuse, and a wide variety of disorders, including schizophrenia and Parkinson's disease. We have previously reported that dopamine depresses excitatory transmission between pyramidal neurons in the prefrontal cortex. Here, using paired recordings, we have investigated dopaminergic modulation of excitatory transmission from pyramidal neurons to fast-spiking (FS) interneurons. In contrast to its effect on recurrent excitation, dopamine was without effect on excitatory transmission to FS interneurons. However, dopamine has directly enhanced the excitability of the FS interneurons to the extent that even a single excitatory postsynaptic potential could initiate spiking with great temporal precision in some of them. These results indicate that dopamine's effects on excitatory transmission are target-specific and that the axon terminals of pyramidal neurons can be selectively regulated at the level of individual synapses. Thus, dopamine's net inhibitory effect on cortical function is remarkably constrained by the nature of the microcircuit elements on which it acts.

  5. Amiodarone reduces depolarization-evoked glutamate release from hippocampual synaptosomes.

    Science.gov (United States)

    Chang, Chia Yu; Hung, Chi Feng; Huang, Shu Kuei; Kuo, Jinn Rung; Wang, Su Jane

    2017-03-01

    Decreased brain glutamate level has emerged as a new therapeutic approach for epilepsy. This study investigated the effect and mechanism of amiodarone, an anti-arrhythmic drug with antiepileptic activity, on glutamate release in the rat hippocampus. In a synaptosomal preparation, amiodarone reduced 4-aminopyridine-evoked Ca2+-dependent glutamate release and cytosolic Ca2+ concentration elevation. Amiodarone did not affect the 4-aminopyridine-evoked depolarization of the synaptosomal membrane potential or the Na+ channel activator veratridine-evoked glutamate release, indicating that the amiodarone-mediated inhibition of glutamate release is not caused by a decrease in synaptosomal excitability. The inhibitory effect of amiodarone on 4-aminopyridine-evoked glutamate release was markedly decreased in synaptosomes pretreated with the Cav2.2 (N-type) and Cav2.1 (P/Q-type) channel blocker ω-conotoxin MVIIC, the calmodulin antagonists W7 and calmidazolium, or the protein kinase A inhibitors H89 and KT5720. However, the intracellular Ca2+-release inhibitors dantrolene and CGP37157 had no effect on the amiodarone-mediated inhibition of glutamate release. Furthermore, amiodarone reduced the frequency of miniature excitatory postsynaptic currents without affecting their amplitude in hippocampal slices. Our data suggest that amiodarone reduces Ca2+ influx through N- and P/Q-type Ca2+ channels, subsequently reducing the Ca2+-calmodulin/protein kinase A cascade to inhibit the evoked glutamate release from rat hippocampal nerve terminals. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  6. 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...

  7. Synergistic effect of repulsive inhibition in synchronization of excitatory networks

    Science.gov (United States)

    Belykh, Igor; Reimbayev, Reimbay; Zhao, Kun

    2015-06-01

    We show that the addition of pairwise repulsive inhibition to excitatory networks of bursting neurons induces synchrony, in contrast to one's expectations. Through stability analysis, we reveal the mechanism underlying this purely synergistic phenomenon and demonstrate that it originates from the transition between different types of bursting, caused by excitatory-inhibitory synaptic coupling. This effect is generic and observed in different models of bursting neurons and fast synaptic interactions. We also find a universal scaling law for the synchronization stability condition for large networks in terms of the number of excitatory and inhibitory inputs each neuron receives, regardless of the network size and topology. This general law is in sharp contrast with linearly coupled networks with positive (attractive) and negative (repulsive) coupling where the placement and structure of negative connections heavily affect synchronization.

  8. Neurotransmitters involved in fast excitatory neurotransmission directly activate enteric glial cells.

    Science.gov (United States)

    Boesmans, W; Cirillo, C; Van den Abbeel, V; Van den Haute, C; Depoortere, I; Tack, J; Vanden Berghe, P

    2013-02-01

    The intimate association between glial cells and neurons within the enteric nervous system has confounded careful examination of the direct responsiveness of enteric glia to different neuroligands. Therefore, we aimed to investigate whether neurotransmitters known to elicit fast excitatory potentials in enteric nerves also activate enteric glia directly. We studied the effect of acetylcholine (ACh), serotonin (5-HT), and adenosine triphosphate (ATP) on intracellular Ca(2+) signaling using aequorin-expressing and Fluo-4 AM-loaded CRL-2690 rat and human enteric glial cell cultures devoid of neurons. The influence of these neurotransmitters on the proliferation of glia was measured and their effect on the expression of c-Fos as well as glial fibrillary acidic protein (GFAP), Sox10, and S100 was examined by immunohistochemistry and quantitative RT-PCR. Apart from ATP, also ACh and 5-HT induced a dose-dependent increase in intracellular Ca(2+) concentration in CRL-2690 cells. Similarly, these neurotransmitters also evoked Ca(2+) transients in human primary enteric glial cells obtained from mucosal biopsies. In contrast with ATP, stimulation with ACh and 5-HT induced early gene expression in CRL-2690 cells. The proliferation of enteric glia and their expression of GFAP, Sox10, and S100 were not affected following stimulation with these neurotransmitters. We provide evidence that enteric glial cells respond to fast excitatory neurotransmitters by changes in intracellular Ca(2+). On the basis of our experimental in vitro setting, we show that enteric glia are not only directly responsive to purinergic but also to serotonergic and cholinergic signaling mechanisms. © 2012 Blackwell Publishing Ltd.

  9. Vestibular evoked myogenic potential

    Directory of Open Access Journals (Sweden)

    Felipe, Lilian

    2012-01-01

    Full Text Available Introduction: The Vestibular Evoked Myogenic Potential (VEMP is a promising test for the evaluation of the cholic descending vestibular system. This reflex depends of the integrity from the saccular macula, from the inferior vestibular nerve, the vestibular nuclei, the vestibule-spinal tract and effectors muscles. Objective: Perform a systematic review of the pertinent literature by means of database (COCHRANE, MEDLINE, LILACS, CAPES. Conclusion: The clinical application of the VEMP has expanded in the last years, as goal that this exam is used as complementary in the otoneurological evaluation currently used. But, methodological issues must be clarified. This way, this method when combined with the standard protocol, can provide a more widely evaluation from the vestibular system. The standardization of the methodology is fundamental criterion for the replicability and sensibility of the exam.

  10. 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.

  11. Adjective metaphors evoke negative meanings.

    Science.gov (United States)

    Sakamoto, Maki; Utsumi, Akira

    2014-01-01

    Previous metaphor studies have paid much attention to nominal metaphors and predicative metaphors, but little attention has been given to adjective metaphors. Although some studies have focused on adjective metaphors, they only examined differences in the acceptability of various types of adjective metaphors. This paper explores the cognitive effects evoked by adjective metaphors. Three psychological experiments revealed that (1) adjective metaphors, especially those modified by color adjectives, tend to evoke negative effect; (2) although the meanings of metaphors are basically affected by the meanings of their vehicles, when a vehicle has a neutral meaning, negative meanings are evoked most frequently for adjective metaphors compared to nominal and predicative metaphors; (3) negative meanings evoked by adjective metaphors are related to poeticness, and poetic metaphors evoke negative meanings more easily than less poetic metaphors. Our research sheds new light on studies of the use of metaphor, which is one of the most basic human cognitive abilities.

  12. Adjective metaphors evoke negative meanings.

    Directory of Open Access Journals (Sweden)

    Maki Sakamoto

    Full Text Available Previous metaphor studies have paid much attention to nominal metaphors and predicative metaphors, but little attention has been given to adjective metaphors. Although some studies have focused on adjective metaphors, they only examined differences in the acceptability of various types of adjective metaphors. This paper explores the cognitive effects evoked by adjective metaphors. Three psychological experiments revealed that (1 adjective metaphors, especially those modified by color adjectives, tend to evoke negative effect; (2 although the meanings of metaphors are basically affected by the meanings of their vehicles, when a vehicle has a neutral meaning, negative meanings are evoked most frequently for adjective metaphors compared to nominal and predicative metaphors; (3 negative meanings evoked by adjective metaphors are related to poeticness, and poetic metaphors evoke negative meanings more easily than less poetic metaphors. Our research sheds new light on studies of the use of metaphor, which is one of the most basic human cognitive abilities.

  13. 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.

  14. Excitatory Neuromodulator Reduces Dopamine Release, Enhancing Prolactin Secretion

    OpenAIRE

    van den Pol, Anthony N.

    2010-01-01

    Hypothalamic dopamine neurons inhibit pituitary prolactin secretion. In this issue, Lyons et al provide evidence for a novel model, whereby the excitatory neuropeptide TRH depolarizes gap junction-coupled dopamine neurons, leading to a shift in the population pattern of action potentials from phasic burst firing to regular tonic firing, hypothetically reducing dopamine release while increasing total spike number.

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

    African Journals Online (AJOL)

    The aim of the present study was to investigate the 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 ...

  16. ARHGAP12 functions as a developmental brake on excitatory synapse function

    NARCIS (Netherlands)

    Ba, W.; Selten, M.M.; van der Raadt, J.; van Veen, H.; Li, L.L.; Benevento, M.; Oudakker, A.R.; Lasabuda, R.S.E.; Letteboer, S.J.; Roepman, R.; van Wezel, Richard Jack Anton; Courtney, M.J.; van Bokhoven, H.; Nadif Kasri, N.

    2016-01-01

    The molecular mechanisms that promote excitatory synapse development have been extensively studied. However, the molecular events preventing precocious excitatory synapse development so that synapses form at the correct time and place are less well understood. Here, we report the functional

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

    Directory of Open Access Journals (Sweden)

    Eva Meier Carlsen

    2014-06-01

    Full Text Available Spinal neuronal networks are essential for motor function. They are involved in the integration of sensory inputs and the generation of rhythmic motor outputs. They continuously adapt their activity to the internal state of the organism and to the environment. This plasticity can be provided 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 by releasing gliotransmitters, which in turn modulate synaptic transmission. Here we investigated if astrocytes present in the ventral horn of the spinal cord modulate synaptic transmission. We evoked synaptic inputs in ventral horn neurons recorded in a slice preparation from the spinal cord of neonatal mice. Neurons responded to electrical stimulation by monosynaptic EPSCs. 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 an inhibition occurring at the presynaptic side of synapses. In the presence of blockers for extracellular ectonucleotidases, TFLLR did not induce presynaptic inhibition. Puffing adenosine reproduced the effect of TFLLR and blocking adenosine A1 receptors with DPCPX prevented it. Altogether our results show that ventral horn astrocytes are responsible for a tonic and a phasic inhibition of excitatory synaptic transmission by releasing ATP, which gets converted into adenosine that binds to inhibitory

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

    Directory of Open Access Journals (Sweden)

    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.

  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. 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...

  1. 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

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

    Directory of Open Access Journals (Sweden)

    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. 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.

  4. A novel excitatory network for the control of breathing

    Science.gov (United States)

    Anderson, Tatiana M.; Garcia, Alfredo J.; Baertsch, Nathan A.; Pollak, Julia; Bloom, Jacob C.; Wei, Aguan D.; Rai, Karan G.; Ramirez, Jan-Marino

    2017-01-01

    Breathing must be tightly coordinated with other behaviors such as vocalization, swallowing, and coughing. These behaviors occur after inspiration, during a respiratory phase termed postinspiration1. Failure to coordinate postinspiration with inspiration can result in aspiration pneumonia, the leading cause of death in Alzheimer’s disease, Parkinson’s disease, dementia, and other neurodegenerative diseases2. Here we describe an excitatory network that generates the neuronal correlate for postinspiratory activity. Glutamatergic-cholinergic neurons form the basis of this network, while GABAergic inhibition establishes the timing and coordination with inspiration. We refer to this novel network as the postinspiratory complex (PiCo). PiCo has autonomous rhythm generating properties and is necessary and sufficient for postinspiratory activity in vivo. PiCo also has distinct responses to neuromodulators when compared with other excitatory brainstem networks. Based on the discovery of PiCo we propose that each of the three phases of breathing is generated by a distinct excitatory network: The preBötzinger complex, which has been linked to inspiration3,4, the PiCo as described here for the neuronal control of postinspiration, and the Lateral parafacial region (pFL) which has been associated with active expiration, a respiratory phase recruited during high metabolic demand4,5,. PMID:27462817

  5. Domestication of the dog from the wolf was promoted by enhanced excitatory synaptic plasticity: a hypothesis.

    Science.gov (United States)

    Li, Yan; Wang, Guo-Dong; Wang, Ming-Shan; Irwin, David M; Wu, Dong-Dong; Zhang, Ya-Ping

    2014-11-05

    Dogs shared a much closer relationship with humans than any other domesticated animals, probably due to their unique social cognitive capabilities, which were hypothesized to be a by-product of selection for tameness toward humans. Here, we demonstrate that genes involved in glutamate metabolism, which account partially for fear response, indeed show the greatest population differentiation by whole-genome comparison of dogs and wolves. However, the changing direction of their expression supports a role in increasing excitatory synaptic plasticity in dogs rather than reducing fear response. Because synaptic plasticity are widely believed to be cellular correlates of learning and memory, this change may alter the learning and memory abilities of ancient scavenging wolves, weaken the fear reaction toward humans, and prompt the initial interspecific contact. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  6. Evoked emotions predict food choice.

    Directory of Open Access Journals (Sweden)

    Jelle R Dalenberg

    Full Text Available 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.

  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. 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.

  9. Layer-Dependent Short-Term Synaptic Plasticity Between Excitatory Neurons in the C2 Barrel Column of Mouse Primary Somatosensory Cortex.

    Science.gov (United States)

    Lefort, Sandrine; Petersen, Carl C H

    2017-07-01

    Neurons process information through spatiotemporal integration of synaptic input. Synaptic transmission between any given pair of neurons is typically a dynamic process with presynaptic action potentials (APs) evoking depressing or facilitating postsynaptic potentials when presynaptic APs occur within hundreds of milliseconds of each other. In order to understand neocortical function, it is therefore important to investigate such short-term synaptic plasticity at synapses between different types of neocortical neurons. Here, we examine short-term synaptic dynamics between excitatory neurons in different layers of the mouse C2 barrel column through in vitro whole-cell recordings. We find layer-dependent short-term plasticity, with depression being dominant at many synaptic connections. Interestingly, however, presynaptic layer 2 neurons predominantly give rise to facilitating excitatory synaptic output at short interspike intervals of 10 and 30 ms. Previous studies have found prominent burst firing of excitatory neurons in supragranular layers of awake mice. The facilitation we observed in the synaptic output of layer 2 may, therefore, be functionally relevant, possibly serving to enhance the postsynaptic impact of burst firing. © The Author 2017. Published by Oxford University Press.

  10. Differential changes in thalamic and cortical excitatory synapses onto striatal spiny projection neurons in a Huntington disease mouse model.

    Science.gov (United States)

    Kolodziejczyk, Karolina; Raymond, Lynn A

    2016-02-01

    Huntington disease (HD), a neurodegenerative disorder caused by CAG repeat expansion in the gene encoding huntingtin, predominantly affects the striatum, especially the spiny projection neurons (SPN). The striatum receives excitatory input from cortex and thalamus, and the role of the former has been well-studied in HD. Here, we report that mutated huntingtin alters function of thalamostriatal connections. We used a novel thalamostriatal (T-S) coculture and an established corticostriatal (C-S) coculture, generated from YAC128 HD and WT (FVB/NJ background strain) mice, to investigate excitatory neurotransmission onto striatal SPN. SPN in T-S coculture from WT mice showed similar mini-excitatory postsynaptic current (mEPSC) frequency and amplitude as in C-S coculture; however, both the frequency and amplitude were significantly reduced in YAC128 T-S coculture. Further investigation in T-S coculture showed similar excitatory synapse density in WT and YAC128 SPN dendrites by immunostaining, suggesting changes in total dendritic length or probability of release as possible explanations for mEPSC frequency changes. Synaptic N-methyl-D-aspartate receptor (NMDAR) current was similar, but extrasynaptic current, associated with cell death signaling, was enhanced in YAC128 SPN in T-S coculture. Employing optical stimulation of cortical versus thalamic afferents and recording from striatal SPN in brain slice, we found increased glutamate release probability and reduced AMPAR/NMDAR current ratios in thalamostriatal synapses, most prominently in YAC128. Enhanced extrasynaptic NMDAR current in YAC128 SPN was apparent with both cortical and thalamic stimulation. We conclude that thalamic afferents to the striatum are affected early, prior to an overt HD phenotype; however, changes in NMDAR localization in SPN are independent of the source of glutamatergic input. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Evoked potentials in pediatric cerebral malaria

    Directory of Open Access Journals (Sweden)

    Minal Bhanushali

    2011-08-01

    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.

  13. New perspectives on vestibular evoked myogenic potentials.

    Science.gov (United States)

    Rosengren, Sally M; Kingma, Herman

    2013-02-01

    Although the vestibular evoked myogenic potential (VEMP) measured from the cervical muscles (cVEMP, cervical VEMP) is well described and has documented clinical utility, its analogue recorded from the extraocular muscles (oVEMP, ocular VEMP) has been described only recently and is currently emerging as an additional test of otolith function. This review will, therefore, summarize recent developments in VEMP research with a focus on the oVEMP. Recent studies suggest that the oVEMP is produced by otolith afferents in the superior vestibular nerve division, whereas the cVEMP evoked by sound is thought to be an inferior vestibular nerve reflex. Correspondingly, the oVEMP correlates better with caloric and subjective visual vertical tests than sound-cVEMPs. cVEMPs are more complicated than often thought, as shown by the presence of crossed responses and conflicting results of recent vibration studies. Altered inner ear mechanics produced by the vestibular diseases superior semicircular canal dehiscence and Ménière's disease lead to changes in the preferred frequency of the oVEMP and cVEMP. The oVEMP provides complementary diagnostic information to the cVEMP and is likely to be a useful addition to the diagnostic test battery in neuro-otology.

  14. Automated determination of excitatory amino acid neurotoxicity in cortical culture.

    Science.gov (United States)

    Klingman, J G; Hartley, D M; Choi, D W

    1990-01-01

    We used a commercially available robotic laboratory workstation to quantitatively study excitotoxic neuronal injury in cell culture. A Beckman Instruments Biomek 1000 was programmed to perform both timed exposures to excitatory amino acid agonists, and kinetic assay of the resultant efflux of lactic dehydrogenase from damaged neurons, using 96-well culture plates. Examination of homocysteate neurotoxicity utilizing this automated method produced results similar to those obtained earlier using manual techniques. The method described here may facilitate the characterization of neurotoxic agonist or antagonist activity.

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

    Directory of Open Access Journals (Sweden)

    Chun-Ping Chu

    Full Text Available BACKGROUND: 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. METHODS AND MAIN RESULTS: 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. CONCLUSIONS: 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.

  16. 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.

  17. Irregular behavior in an excitatory-inhibitory neuronal network.

    Science.gov (United States)

    Park, Choongseok; Terman, David

    2010-06-01

    Excitatory-inhibitory networks arise in many regions throughout the central nervous system and display complex spatiotemporal firing patterns. These neuronal activity patterns (of individual neurons and/or the whole network) are closely related to the functional status of the system and differ between normal and pathological states. For example, neurons within the basal ganglia, a group of subcortical nuclei that are responsible for the generation of movement, display a variety of dynamic behaviors such as correlated oscillatory activity and irregular, uncorrelated spiking. Neither the origins of these firing patterns nor the mechanisms that underlie the patterns are well understood. We consider a biophysical model of an excitatory-inhibitory network in the basal ganglia and explore how specific biophysical properties of the network contribute to the generation of irregular spiking. We use geometric dynamical systems and singular perturbation methods to systematically reduce the model to a simpler set of equations, which is suitable for analysis. The results specify the dependence on the strengths of synaptic connections and the intrinsic firing properties of the cells in the irregular regime when applied to the subthalamopallidal network of the basal ganglia. (c) 2010 American Institute of Physics.

  18. The Role of TSC1 in the Formation and Maintenance of Excitatory Synapses

    National Research Council Canada - National Science Library

    Sabatini, Bernardo L

    2005-01-01

    .... Functional analysis reveals these morphological changes are accompanied by perturbation of electrophysiological properties, including changes in strength and glutamate receptor composition of excitatory synapses...

  19. Impaired Excitatory Neurotransmission in the Urinary Bladder from the Obese Zucker Rat: Role of Cannabinoid Receptors.

    Directory of Open Access Journals (Sweden)

    Igor Blaha

    Full Text Available Metabolic syndrome (MS is a known risk factor for lower urinary tract symptoms. This study investigates whether functional and expression changes of cannabinoid CB1 and CB2 receptors are involved in the bladder dysfunction in an obese rat model with insulin resistance. Bladder samples from obese Zucker rat (OZR and their respective controls lean Zucker rat (LZR were processed for immunohistochemistry and western blot for studying the cannabinoid receptors expression. Detrusor smooth muscle (DSM strips from LZR and OZR were also mounted in myographs for isometric force recordings. Neuronal and smooth muscle CB1 and CB2 receptor expression and the nerve fiber density was diminished in the OZR bladder. Electrical field stimulation (EFS and acetylcholine (ACh induced frequency- and concentration-dependent contractions of LZR and OZR DSM. ACh contractile responses were similar in LZR and OZR. EFS-elicited contractions, however, were reduced in OZR bladder. Cannabinoid receptor agonists and antagonists failed to modify the DSM basal tension in LZR and OZR In LZR bladder, EFS responses were inhibited by ACEA and SER-601, CB1 and CB2 receptor agonists, respectively, these effects being reversed by ACEA plus the CB1 antagonist, AM-251 or SER-601 plus the CB2 antagonist, AM-630. In OZR bladder, the inhibitory action of ACEA on nerve-evoked contractions was diminished, whereas that SER-601 did not change EFS responses. These results suggest that a diminished function and expression of neuronal cannabinoid CB1 and CB2 receptors, as well as a lower nerve fiber density is involved in the impaired excitatory neurotransmission of the urinary bladder from the OZR.

  20. Activity-dependent endogenous taurine release facilitates excitatory neurotransmission in the neocortical marginal zone of neonatal rats

    Directory of Open Access Journals (Sweden)

    Taizhe eQian

    2014-02-01

    Full Text Available In the developing cerebral cortex, the marginal zone (MZ, consisting of early-generated neurons such as Cajal-Retzius cells, plays an important role in cell migration and lamination. There is accumulating evidence of widespread excitatory neurotransmission mediated by γ-aminobutyric acid (GABA in the MZ. Cajal-Retzius cells express not only GABAA receptors but also α2/β subunits of glycine receptors, and exhibit glycine receptor-mediated depolarization due to high [Cl−]i. However, the physiological roles of glycine receptors and their endogenous agonists during neurotransmission in the MZ are yet to be elucidated. To address this question, we performed optical imaging from the MZ using the voltage-sensitive dye JPW1114 on tangential neocortical slices of neonatal rats. A single electrical stimulus evoked an action-potential-dependent optical signal that spread radially over the MZ. The amplitude of the signal was not affected by glutamate receptor blockers, but was suppressed by either GABAA or glycine receptor antagonists. Combined application of both antagonists nearly abolished the signal. Inhibition of Na+, K+-2Cl− cotransporter by 20 µM bumetanide reduced the signal, indicating that this transporter contributes to excitation. Analysis of the interstitial fluid obtained by microdialysis from tangential neocortical slices with high-performance liquid chromatography revealed that GABA and taurine, but not glycine or glutamate, were released in the MZ in response to the electrical stimulation. The ambient release of taurine was reduced by the addition of a voltage-sensitive Na+ channel blocker. Immunohistochemistry and immunoelectron microscopy indicated that taurine was stored both in Cajal-Retzius and non-Cajal-Retzius cells in the MZ, but was not localized in presynaptic structures. Our results suggest that activity-dependent non-synaptic release of endogenous taurine facilitates excitatory neurotransmission through activation of

  1. 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 inhibition

  2. L-DOPA inhibits excitatory synaptic transmission in the rat nucleus tractus solitarius through release of dopamine.

    Science.gov (United States)

    Ohi, Y; Kodama, D; Haji, A

    2017-09-30

    The mode of action of L-DOPA on excitatory synaptic transmission in second-order neurons of the nucleus tractus solitarius (NTS) was studied using the rat brainstem slices. Superfusion of L-DOPA (10μM) reduced the frequency of miniature excitatory postsynaptic currents (mEPSCs) without any effect on the amplitude. A low concentration (1μM) was ineffective on the mEPSCs, and the highest concentration (100μM) exerted a stronger inhibitory effect. L-DOPA (10μM) decreased the amplitude of EPSCs (eEPSCs) evoked by electrical stimulation of the tractus solitarius and increased the paired-pulse ratio. The inhibitory effects of L-DOPA on mEPSCs and eEPSCs were similar to those of dopamine (100μM). The effects of L-DOPA were blocked by a competitive antagonist, L-DOPA methyl ester (100μM) and also by a D2 receptor antagonist, sulpiride (10μM), while those of dopamine were blocked by the latter but not by the former. In reserpine (5mg/kg, s.c.)-treated rats, the effects of L-DOPA on both mEPSCs and eEPSCs were completely abolished, but those of dopamine remained unchanged. The present results suggest a possibility that L-DOPA may induce the release of dopamine from the axon terminals in the NTS and the released dopamine suppresses the glutamatergic transmission through activation of the presynaptic D2 receptors. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. Evoked Emotions Predict Food Choice

    OpenAIRE

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

    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 ...

  4. EVOKED CAVERNOUS ACTIVITY: NEUROANATOMIC IMPLICATIONS

    OpenAIRE

    Yilmaz, Ugur; Vicars, Brenda; Yang, Claire C.

    2009-01-01

    We investigated the autonomic innervation of the penis by using evoked cavernous activity (ECA). We recruited 7 males with thoracic spinal cord injury (SCI) and sexual dysfunction and 6 males who were scheduled to have pelvic surgery (PS), specifically non-nerve-sparing radical cystoprostatectomy. In the PS subjects, ECA was performed both pre- and postoperatively. The left median nerve was electrically stimulated and ECA was recorded with two concentric electromyography needles placed into t...

  5. Model of evoked rabbit phonation.

    Science.gov (United States)

    Ge, Ping Jiang; French, Lesley C; Ohno, Tsunehisa; Zealear, David L; Rousseau, Bernard

    2009-01-01

    We describe a method for eliciting phonation in an in vivo rabbit preparation using low-frequency, bipolar pulsed stimulation of the cricothyroid muscles with airflow delivered to the glottis. Ten New Zealand White breeder rabbits weighing 3 to 5 kg were used in this study. The cricothyroid muscles were isolated bilaterally, and separate pairs of anode-cathode hooked-wire electrodes were inserted into each muscle. A Grass S-88 stimulator and 2 constant-current PSIU6 isolation units were used to deliver bipolar square wave pulses to each cricothyroid muscle, with airflow delivered to the glottis through a cuffed endotracheal tube. Phonation was evoked with a 50-Hz, 4-mA stimulus train of 1-ms pulses delivered to each cricothyroid muscle. The pulse trains were on for 2 seconds and were repeated every 5 seconds over a period of 180 minutes. Airflow was delivered at 143 cm3/s, producing phonation measuring 71 to 85 dB sound pressure level. Evoked phonation is feasible in rabbits by use of bipolar stimulation of the cricothyroid muscles with airflow delivered to the glottis. The in vivo rabbit preparation described may provide a useful small animal option for studies of evoked phonation. From the level and consistency of the adduction observed, we hypothesize that current spreading to the underlying adductor muscles and nerves resulted in neural pathway involvement beyond discrete activation of the cricothyroid muscle, providing sufficient approximation of the vocal folds for phonation.

  6. Optimal properties of analog perceptrons with excitatory weights.

    Directory of Open Access Journals (Sweden)

    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.

  7. Psychopathology of excitatory and compulsive aspects of vandalistic graffiti.

    Science.gov (United States)

    Pani, Roberto; Sagliaschi, Samanta

    2009-12-01

    In this paper were explored psychological themes underlying vandalistic graffiti by 162 Italian adolescents (154 boys, 8 girls; M age = 17.5 yr., SD = 2.3) who "felt hooked" on vandalistic graffiti and agreed to participate in an interview with a graffiti writer. Use of this interview could clarify the motivations which led these youths to write on walls, the meaning they give to that act, the emotions they feel as they write, and their perception of risks and excitement involved. Qualitative analysis of their responses suggested these adolescents present a marked excitatory-compulsive trait, report a sense of emptiness, boredom, loneliness, and a lack of internal points of reference, and adopt behaviors linked to a pressing need for immediate gratification.

  8. Disrupted-in-schizophrenia1 (DISC1) L100P mutation alters synaptic transmission and plasticity in the hippocampus and causes recognition memory deficits.

    Science.gov (United States)

    Cui, Lin; Sun, Wei; Yu, Ming; Li, Nan; Guo, Li; Gu, Huating; Zhou, Yu

    2016-10-12

    Disrupted-in-schizophrenia 1(DISC1) is a promising candidate susceptibility gene for a spectrum of psychiatric illnesses that share cognitive impairments in common, including schizophrenia, bipolar disorder and major depression. Here we report that DISC1 L100P homozygous mutant shows normal anxiety- and depression-like behavior, but impaired object recognition which is prevented by administration of atypical antipsychotic drug clozapine. Ca2+ image analysis reveals suppression of glutamate-evoked elevation of cytoplasmic [Ca2+] in L100P hippocampal slices. L100P mutant slices exhibit decreased excitatory synaptic transmission (sEPSCs and mEPSCs) in dentate gyrus (DG) and impaired long-term potentiation in the CA1 region of the hippocampus. L100P mutation does not alter proteins expression of the excitatory synaptic markers, PSD95 and synapsin-1; neither does it changes dendrites morphology of primary cultured hippocampal neurons. Our findings suggest that the existence of abnormal synaptic transmission and plasticity in hippocampal network may disrupt declarative information processing and contribute to recognition deficits in DISC1 L100P mutant mice.

  9. ARHGAP12 Functions as a Developmental Brake on Excitatory Synapse Function

    Directory of Open Access Journals (Sweden)

    W. Ba

    2016-02-01

    Full Text Available The molecular mechanisms that promote excitatory synapse development have been extensively studied. However, the molecular events preventing precocious excitatory synapse development so that synapses form at the correct time and place are less well understood. Here, we report the functional characterization of ARHGAP12, a previously uncharacterized Rho GTPase-activating protein (RhoGAP in the brain. ARHGAP12 is specifically expressed in the CA1 region of the hippocampus, where it localizes to the postsynaptic compartment of excitatory synapses. ARHGAP12 negatively controls spine size via its RhoGAP activity and promotes, by interacting with CIP4, postsynaptic AMPA receptor endocytosis. Arhgap12 knockdown results in precocious maturation of excitatory synapses, as indicated by a reduction in the proportion of silent synapses. Collectively, our data show that ARHGAP12 is a synaptic RhoGAP that regulates excitatory synaptic structure and function during development.

  10. Auditory evoked potentials in children and adolescents with Down syndrome.

    Science.gov (United States)

    Gregory, Letícia; Rosa, Rafael F M; Zen, Paulo R G; Sleifer, Pricila

    2018-01-01

    Down syndrome, or trisomy 21, is the most common genetic alteration in humans. The syndrome presents with several features, including hearing loss and changes in the central nervous system, which may affect language development in children and lead to school difficulties. The present study aimed to investigate group differences in the central auditory system by long-latency auditory evoked potentials and cognitive potential. An assessment of 23 children and adolescents with Down syndrome was performed, and a control group composed of 43 children and adolescents without genetic and/or neurological changes was used for comparison. All children underwent evaluation with pure tone and vocal audiometry, acoustic immitance measures, long-latency auditory evoked potentials, and cognitive potential. Longer latencies of the waves were found in the Down syndrome group than the control group, without significant differences in amplitude, suggesting that individuals with Down syndrome have difficulty in discrimination and auditory memory. It is, therefore, important to stimulate and monitor these children in order to enable adequate development and improve their life quality. We also emphasize the importance of the application of auditory evoked potentials in clinical practice, in order to contribute to the early diagnosis of hearing alterations and the development of more research in this area. © 2017 Wiley Periodicals, Inc.

  11. Achieving Presence through Evoked Reality

    Science.gov (United States)

    Pillai, Jayesh S.; Schmidt, Colin; Richir, Simon

    2013-01-01

    The sense of “Presence” (evolving from “telepresence”) has always been associated with virtual reality research and is still an exceptionally mystifying constituent. Now the study of presence clearly spans over various disciplines associated with cognition. This paper attempts to put forth a concept that argues that it’s an experience of an “Evoked Reality (ER)” (illusion of reality) that triggers an “Evoked Presence (EP)” (sense of presence) in our minds. A Three Pole Reality Model is proposed to explain this phenomenon. The poles range from Dream Reality to Simulated Reality with Primary (Physical) Reality at the center. To demonstrate the relationship between ER and EP, a Reality-Presence Map is developed. We believe that this concept of ER and the proposed model may have significant applications in the study of presence, and in exploring the possibilities of not just virtual reality but also what we call “reality.” PMID:23550234

  12. Evoked Electromyographically Controlled Electrical Stimulation

    Directory of Open Access Journals (Sweden)

    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.

  13. Methamphetamine-evoked depression of GABAB receptor signaling in GABA neurons of the VTA

    Science.gov (United States)

    Padgett, CL; Lalive, AL; Tan, KR; Terunuma, M; Munoz, MB; Pangalos, MN; Martínez-Hernández, J; Watanabe, M; Moss, SJ; Luján, R; Lüscher, C; Slesinger, PA

    2012-01-01

    Psychostimulants induce neuroadaptations in excitatory and fast inhibitory transmission in the ventral tegmental area (VTA). Mechanisms underlying drug-evoked synaptic plasticity of slow inhibitory transmission mediated by GABAB receptors and G protein-gated inwardly rectifying potassium (GIRK/Kir3) channels, however, are poorly understood. Here, we show that one day after methamphetamine (METH) or cocaine exposure, both synaptically-evoked and baclofen-activated GABABR-GIRK currents were significantly depressed in VTA GABA neurons, and remained depressed for 7 days. Presynaptic inhibition mediated by GABABRs on GABA terminals was also weakened. Quantitative immunoelectron microscopy revealed internalization of GABAB1R and GIRK2, which occurred coincident with dephosphorylation of Ser783 in GABAB2R, a site implicated in regulating GABABR surface expression. Inhibition of protein phosphatases recovered GABABR-GIRK currents in VTA GABA neurons of METH-injected mice. This psychostimulant-evoked impairment in GABABR signaling removes an intrinsic brake on GABA neuron spiking, which may augment GABA transmission in the mesocorticolimbic system. PMID:22405207

  14. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  16. The Abused Inhalant Toluene Differentially Modulates Excitatory and Inhibitory Synaptic Transmission in Deep-Layer Neurons of the Medial Prefrontal Cortex

    Science.gov (United States)

    Beckley, Jacob T; Woodward, John J

    2011-01-01

    Volatile organic solvents such as toluene are voluntarily inhaled for their intoxicating effects. Solvent use is especially prevalent among adolescents, and is associated with deficits in a wide range of cognitive tasks including attention, behavioral control, and risk assessment. Despite these findings, little is known about the effects of toluene on brain areas mediating these behaviors. In this study, whole-cell patch-clamp recordings were used to determine the effect toluene on neurons within the medial PFC, a region critically involved in cognitive function. Toluene had no effect on measures of intrinsic excitability, but enhanced stimulus-evoked γ-amino butyric acid A-mediated inhibitory postsynaptic currents (IPSCs). In the presence of tetrodotoxin (TTX) to block action potentials, toluene increased the frequency and amplitude of miniature IPSCs. In contrast, toluene induced a delayed but persistent decrease in evoked or spontaneous AMPA-mediated excitatory postsynaptic currents (EPSCs). This effect was prevented by an intracellular calcium chelator or by the ryanodine receptor and SERCA inhibitors, dantrolene or thapsigargin, respectively, suggesting that toluene may mobilize intracellular calcium pools. The toluene-induced reduction in AMPA EPSCs was also prevented by a cannabinoid receptor (CB1R) antagonist, and was occluded by the CB1 agonist WIN 55,212-2 that itself induced a profound decrease in AMPA-mediated EPSCs. Toluene had no effect on the frequency or amplitude of miniature EPSCs recorded in the presence of TTX. Finally, toluene dose-dependently inhibited N-methyl--aspartate (NMDA)-mediated EPSCs and the magnitude and reversibility of this effect was CB1R sensitive indicating both direct and indirect actions of toluene on NMDA-mediated responses. Together, these results suggest that the effect of toluene on cognitive behaviors may result from its action on inhibitory and excitatory synaptic transmission of PFC neurons. PMID:21430649

  17. Evoked otoacoustic emissions behaviour in retinitis pigmentosa.

    Science.gov (United States)

    Fiore, C; Cagini, C; Menduno, P; Toniassoni, I; Desantis, A; Pennacchi, A; Ricci, G; Molini, E

    1994-01-01

    The hearing function was studied in 26 patients affected by retinitis pigmentosa (RP) and in their relatives. Sixteen patients showed bilateral normal hearing when examined with traditional audiometric methods. In these normoacusic patients evoked otoacoustic emissions (EOE) have been studied. The EOE offer a unique opportunity to measure objectively the function of outer hair cells: they record the amplitude of the energy produced by the outer hair cells of the coclea following an acoustic stimulation. The data have been statistically compared, using the Student's t-test, with those obtained in a homogeneous control-group of normal subjects. In normoacusic subjects with RP the average values of EOE intensity are statistically lower than those of normal subjects in 64 of the 127 frequency bands examined. Moreover, the distribution of the EOE in patients with retinitis pigmentosa proved to be more discontinous than that observed in the normal subjects. The EOE recorded in 14 normoacusic relatives show in some cases small anomalies but the data, on account of the limited sample group, cannot be statistically evaluated. Therefore a subclinical alteration of the Organ of Corti is found in 100% of the patients affected by RP, although they appear to be normoacusic to usual audiometric tests.

  18. Motor effects of intracaudate injection of excitatory amino acids.

    Science.gov (United States)

    Toth, E; Lajtha, A

    1989-05-01

    In a study of the role of excitatory amino acid receptors in movement disorders, the effect of the injection of glutamate (Glu), aspartate (Asp), N-methyl-D-aspartate (NMDA), quisqualate (Qu), or kainate (K) into the rat striatum was investigated. Rats were microinjected unilaterally through chronically implanted guide cannulas and their motor behavior was recorded. After 10-25 min L-Glu produced reversible periodic choreiform movements lasting 5-10 sec and contraversive rotation lasting 1-2 min. Both episodes were repeated every 2-3 min: the duration of motor effects was 60-80 min. L-Asp had an effect similar to that of L-Glu and in addition produced barrel rolling. The L-isomers of both Glu and Asp were active and the D-isomers were inactive. NMDA, Qu, and K were more potent than Glu or Asp. Each produced effects similar to that of Glu, and in addition NMDA and K produced wet-dog-shakes and masticatory movements. The motor behavior produced by Qu was identical to that of Glu, but it lasted longer. The motor effects of L-Glu were blocked by L-glutamic acid diethyl ester (GDEE) and by a larger sedative dose of 2-amino-5-phosphonopentanoic acid (AP5), but not by haloperidol, GABA, glycine (Gly), or a smaller nonsedative dose of AP5. The results suggest that the motor effects of L-Glu were produced by activation of the Qu-type (glutamatergic) receptors, not involving the dopamine and GABA systems. However, activation of the K-type receptors by L-Glu cannot be ruled out.

  19. Criticality predicts maximum irregularity in recurrent networks of excitatory nodes.

    Directory of Open Access Journals (Sweden)

    Yahya Karimipanah

    Full Text Available A rigorous understanding of brain dynamics and function requires a conceptual bridge between multiple levels of organization, including neural spiking and network-level population activity. Mounting evidence suggests that neural networks of cerebral cortex operate at a critical regime, which is defined as a transition point between two phases of short lasting and chaotic activity. However, despite the fact that criticality brings about certain functional advantages for information processing, its supporting evidence is still far from conclusive, as it has been mostly based on power law scaling of size and durations of cascades of activity. Moreover, to what degree such hypothesis could explain some fundamental features of neural activity is still largely unknown. One of the most prevalent features of cortical activity in vivo is known to be spike irregularity of spike trains, which is measured in terms of the coefficient of variation (CV larger than one. Here, using a minimal computational model of excitatory nodes, we show that irregular spiking (CV > 1 naturally emerges in a recurrent network operating at criticality. More importantly, we show that even at the presence of other sources of spike irregularity, being at criticality maximizes the mean coefficient of variation of neurons, thereby maximizing their spike irregularity. Furthermore, we also show that such a maximized irregularity results in maximum correlation between neuronal firing rates and their corresponding spike irregularity (measured in terms of CV. On the one hand, using a model in the universality class of directed percolation, we propose new hallmarks of criticality at single-unit level, which could be applicable to any network of excitable nodes. On the other hand, given the controversy of the neural criticality hypothesis, we discuss the limitation of this approach to neural systems and to what degree they support the criticality hypothesis in real neural networks. Finally

  20. Control of excitatory CNS synaptogenesis by astrocyte-secreted proteins Hevin and SPARC

    National Research Council Canada - National Science Library

    Hakan Kucukdereli; Nicola J. Allen; Anthony T. Lee; Ava Feng; M. Ilcim Ozlu; Laura M. Conatser; Chandrani Chakraborty; Gail Workman; Matthew Weaver; E. Helene Sage; Ben A. Barres; Cagla Eroglu

    2011-01-01

    Astrocytes regulate synaptic connectivity in the CNS through secreted signals. Here we identified two astrocyte-secreted proteins, hevin and SPARC, as regulators of excitatory synaptogenesis in vitro and in vivo...

  1. Comparison of binaural auditory brainstem responses and the binaural difference potential evoked by chirps and clicks.

    Science.gov (United States)

    Riedel, Helmut; Kollmeier, Birger

    2002-07-01

    Rising chirps that compensate for the dispersion of the travelling wave on the basilar membrane evoke larger monaural brainstem responses than clicks. In order to test if a similar effect applies for the early processing stages of binaural information, monaurally and binaurally evoked auditory brainstem responses were recorded for clicks and chirps for levels from 10 to 60 dB nHL in steps of 10 dB. Ten thousand sweeps were collected for every stimulus condition from 10 normal hearing subjects. Wave V amplitudes are significantly larger for chirps than for clicks for all conditions. The amplitude of the binaural difference potential, DP1-DN1, is significantly larger for chirps at the levels 30 and 40 dB nHL. Both the binaurally evoked potential and the binaural difference potential exhibit steeper growth functions for chirps than for clicks for levels up to 40 dB nHL. For higher stimulation levels the chirp responses saturate approaching the click evoked amplitude. For both stimuli the latency of DP1 is shorter than the latency of the binaural wave V, which in turn is shorter than the latency of DN1. The amplitude ratio of the binaural difference potential to the binaural response is independent of stimulus level for clicks and chirps. A possible interpretation is that with click stimulation predominantly binaural interaction from high frequency regions is seen which is compatible with a processing by contralateral inhibitory and ipsilateral excitatory (IE) cells. Contributions from low frequencies are negligible since the responses from low frequencies are not synchronized for clicks. The improved synchronization at lower frequencies using chirp stimuli yields contributions from both low and high frequency neurons enlarging the amplitudes of the binaural responses as well as the binaural difference potential. Since the constant amplitude ratio of the binaural difference potential to the binaural response makes contralateral and ipsilateral excitatory interaction

  2. Influence of delta9-tetrahydrocannabinol and cannabidiol on photically evoked after-discharge potentials.

    Science.gov (United States)

    Turkanis, S A; Chiu, P; Borys, H K; Karler, R

    1977-04-29

    Two cannabinoids, delta9-tetrahydrocannabinol and cannabidiol, and several reference drugs were compared relative to their effects in a recently developed anticonvulsant test system, the after-discharge potentials of the visually evoked response; the potentials were recorded electrophysiologically from electrodes permanently mounted over the visual cortices of conscious rats. In anticonvulsant doses, trimethadione and ethosuximide produced an extensive depression of after-discharge activity, whereas diphenylhydantoin and cannabidiol exerted no such effect. In contrast, anticonvulsant doses of delta9-tetrahydrocannabinol and subconvulsant doses of pentylenetetrazol markedly increased after-discharge activity, which may represent a manifestation of their central nervous system excitatory properties. The data from the present study support our previously published ovservations from several other anticonvulsant tests that indicate the anticonvulsant characteristics of cannabidiol resemble those of diphenylhydantoin rather than those of trimethadione and that the central excitatory properties of delta9-tetrahydrocannabinol distinguish it from cannabidiol. The results consistently suggest that the cannabinoids will be effective against grand mal but not absence seizures.

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

    Directory of Open Access Journals (Sweden)

    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

  4. Ocular Vestibular Evoked Myogenic Potentials

    Directory of Open Access Journals (Sweden)

    Felipe, Lilian

    2014-01-01

    Full Text Available Introduction Diagnostic testing of the vestibular system is an essential component of treating patients with balance dysfunction. Until recently, testing methods primarily evaluated the integrity of the horizontal semicircular canal, which is only a portion of the vestibular system. Recent advances in technology have afforded clinicians the ability to assess otolith function through vestibular evoked myogenic potential (VEMP testing. VEMP testing from the inferior extraocular muscles of the eye has been the subject of interest of recent research. Objective To summarize recent developments in ocular VEMP testing. Results Recent studies suggest that the ocular VEMP is produced by otolith afferents in the superior division of the vestibular nerve. The ocular VEMP is a short latency potential, composed of extraocular myogenic responses activated by sound stimulation and registered by surface electromyography via ipsilateral otolithic and contralateral extraocular muscle activation. The inferior oblique muscle is the most superficial of the six extraocular muscles responsible for eye movement. Therefore, measurement of ocular VEMPs can be performed easily by using surface electrodes on the skin below the eyes contralateral to the stimulated side. Conclusion This new variation of the VEMP procedure may supplement conventional testing in difficult to test populations. It may also be possible to use this technique to evaluate previously inaccessible information on the vestibular system.

  5. Evoked cavernous activity: neuroanatomic implications.

    Science.gov (United States)

    Yilmaz, U; Vicars, B; Yang, C C

    2009-01-01

    We investigated the autonomic innervation of the penis by using evoked cavernous activity (ECA). We recruited seven men with thoracic spinal cord injury (SCI) and sexual dysfunction, and six men who were scheduled to have pelvic surgery (PS), specifically non-nerve-sparing radical cystoprostatectomy. In the PS patients, ECA was performed both pre- and postoperatively. The left median nerve was electrically stimulated and ECA was recorded with two concentric electromyography needles placed into the right and left cavernous bodies. We simultaneously recorded hand and foot sympathetic skin responses (SSRs) as controls. In the SCI group, all but one patient had reproducible hand SSRs. None of these patients had ECA or foot SSRs. All the PS patients had reproducible ECA and SSRs, both preoperatively and postoperatively. There was no difference in the latency and amplitude measurements of ECA and SSRs in the postoperative compared with that of the pre-operative period (P>0.05). In conclusion, ECA is absent in men with SCI above the sympathetic outflow to the genitalia. In men, after radical pelvic surgery, ECA is preserved, indicating the preservation of sympathetic fibers.

  6. Evoked potentials in neuroinfections in children

    Directory of Open Access Journals (Sweden)

    V. N. Komantsev

    2013-01-01

    Full Text Available We present the results of the neurophysiological study in which 95 children with viral encephalitis and 30 children with meningitis (age from 2 up to 17 years undergo evoked potentials investigation. Some specific features of evoked potentials in neuroinfections have been shown to correlate with the course of disease and the age of the patients. We give a description of a logistic model of predicting outcomes in such patients by complex diagnostic method. We have found that evoked potentials may be successfully implemented in correcting the therapeutic strategies. Study of evoked potentials in neuroinfections in children can define the severity and extent of lesions and help to identify subclinical dysfunction and monitor the recovery processes under the therapy.

  7. Visual Evoked Potentials in Rett Syndrome

    Directory of Open Access Journals (Sweden)

    J. Gordon Millichap

    2015-11-01

    Full Text Available Investigators from the Boston Children's Hospital recorded pattern-reversal visual evoked potentials (VEPs in Mecp2 heterozygous female mice and in 34 girls with Rett syndrome (RTT.

  8. Learning alters theta amplitude, theta-gamma coupling and neuronal synchronization in inferotemporal cortex

    Directory of Open Access Journals (Sweden)

    Nicol Alister U

    2011-06-01

    Full Text Available Abstract Background How oscillatory brain rhythms alone, or in combination, influence cortical information processing to support learning has yet to be fully established. Local field potential and multi-unit neuronal activity recordings were made from 64-electrode arrays in the inferotemporal cortex of conscious sheep during and after visual discrimination learning of face or object pairs. A neural network model has been developed to simulate and aid functional interpretation of learning-evoked changes. Results Following learning the amplitude of theta (4-8 Hz, but not gamma (30-70 Hz oscillations was increased, as was the ratio of theta to gamma. Over 75% of electrodes showed significant coupling between theta phase and gamma amplitude (theta-nested gamma. The strength of this coupling was also increased following learning and this was not simply a consequence of increased theta amplitude. Actual discrimination performance was significantly correlated with theta and theta-gamma coupling changes. Neuronal activity was phase-locked with theta but learning had no effect on firing rates or the magnitude or latencies of visual evoked potentials during stimuli. The neural network model developed showed that a combination of fast and slow inhibitory interneurons could generate theta-nested gamma. By increasing N-methyl-D-aspartate receptor sensitivity in the model similar changes were produced as in inferotemporal cortex after learning. The model showed that these changes could potentiate the firing of downstream neurons by a temporal desynchronization of excitatory neuron output without increasing the firing frequencies of the latter. This desynchronization effect was confirmed in IT neuronal activity following learning and its magnitude was correlated with discrimination performance. Conclusions Face discrimination learning produces significant increases in both theta amplitude and the strength of theta-gamma coupling in the inferotemporal cortex

  9. Investigating the roles of odor-evoked oscillations in information processing in the turtle olfactory bulb

    Science.gov (United States)

    Kim, Soyoun

    It has been earlier established that presentation of an odorant stimulus to the turtle evokes specific spatio-temporal responses in the olfactory bulb. This response includes three distinct oscillatory patterns (rostral, middle and caudal) that have different spatial (locations and scopes) and temporal (frequencies and delay from the odorant onset) properties. In this thesis we investigate, using modeling and experimental approaches; the mechanisms of formation and the role of the oscillatory patterning in the turtle olfactory bulb. We have built a computational model that incorporates the basic anatomy and neurophysiology of the olfactory bulb to investigate how the observed patterns relate to activity of individual neurons and what roles they could play in olfactory information processing. We show that three basic anatomical/physiological properties of the olfactory network underlie formation of a temporal sequence of simultaneous activations of glomerular modules: fast synaptic inhibition between populations of excitatory and inhibitory cells, slow self-inhibition observed on excitatory cells; and input strength. The model suggests that the role of oscillations is to organize the neural activity in a temporal sequence which groups the activation of glomerular modules based on the input strength similarity. We show that this type of code explains particularly well the experimental findings reported also by other groups, showing that temporal patterning may mediate discrimination of similar odorants. Furthermore, we showed that within our model, feedback from cortical regions of the brain could modulate oscillatory patterning and provide mechanisms to generate experimentally observed period doubling in one of the oscillations. This requires the cortical processing to act as a type of coincidence modulator and provide functional coupling between excitatory modules that is absent in the bulbar network. This hypothesis is partially supported by our experiments that

  10. Extensive excitatory network interactions shape temporal processing of communication signals in a model sensory system.

    Science.gov (United States)

    Ma, Xiaofeng; Kohashi, Tsunehiko; Carlson, Bruce A

    2013-07-01

    Many sensory brain regions are characterized by extensive local network interactions. However, we know relatively little about the contribution of this microcircuitry to sensory coding. Detailed analyses of neuronal microcircuitry are usually performed in vitro, whereas sensory processing is typically studied by recording from individual neurons in vivo. The electrosensory pathway of mormyrid fish provides a unique opportunity to link in vitro studies of synaptic physiology with in vivo studies of sensory processing. These fish communicate by actively varying the intervals between pulses of electricity. Within the midbrain posterior exterolateral nucleus (ELp), the temporal filtering of afferent spike trains establishes interval tuning by single neurons. We characterized pairwise neuronal connectivity among ELp neurons with dual whole cell recording in an in vitro whole brain preparation. We found a densely connected network in which single neurons influenced the responses of other neurons throughout the network. Similarly tuned neurons were more likely to share an excitatory synaptic connection than differently tuned neurons, and synaptic connections between similarly tuned neurons were stronger than connections between differently tuned neurons. We propose a general model for excitatory network interactions in which strong excitatory connections both reinforce and adjust tuning and weak excitatory connections make smaller modifications to tuning. The diversity of interval tuning observed among this population of neurons can be explained, in part, by each individual neuron receiving a different complement of local excitatory inputs.

  11. 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.

  12. 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 ...... of EAATs and their intricate transport process, the novel approaches to pharmacological modulation of the transporters that have emerged, and interesting new perspectives in EAAT as drug targets proposed in recent years....

  13. 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.

  14. 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 IC50 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.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    localization can buffer nearby glutamate receptors and modulate excitatory neurotransmission and synaptic plasticity. It is also the main neuronal cysteine uptake system acting as the rate-limiting factor for the synthesis of glutathione, a potent antioxidant, in EAAT3 expressing neurons, while on GABAergic......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...

  16. 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.

  17. Excitatory effects of thyrotropin-releasing hormone (TRH) in hypoglossal motoneurons

    DEFF Research Database (Denmark)

    Rekling, J C

    1990-01-01

    The effect of thyrotropin-releasing hormone (TRH) was studied in 30 hypoglossal motoneurons from brainstem slices of guinea pigs. Bath application of TRH resulted in an increase of the spontaneous excitatory synaptic activity, depolarization of the neurons, increase of the input resistance...

  18. Excitatory amino acid release and electrocortical brain activity after hypoxemia in near-term lambs.

    NARCIS (Netherlands)

    Os, S.H.G. van; Ruitenbeek, W.; Hopman, J.; Bor, M. van de

    2006-01-01

    BACKGROUND: Energy failure due to insufficient cerebral O(2)-supply leads to excess accumulation of calcium ions in presynaptic neurons, followed by excess release of excitatory amino acids (EAAs), which are potent neurotoxins, into the synaptic cleft. AIM: The aim of the present study was to

  19. 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.

  20. 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.

  1. Evoked response audiometry in scrub typhus: prospective, randomised, case-control study.

    Science.gov (United States)

    Thakur, J S; Mohindroo, N K; Sharma, D R; Soni, K; Kaushal, S S

    2011-06-01

    To investigate the hypothesis of cochlear and retrocochlear damage in scrub typhus, using evoked response audiometry. Prospective, randomised, case-control study. The study included 25 patients with scrub typhus and 25 controls with other febrile illnesses not known to cause hearing loss. Controls were age- and sex-matched. All subjects underwent pure tone audiometry and evoked response audiometry before commencing treatment. Six patients presented with hearing loss, although a total of 23 patients had evidence of symmetrical high frequency loss on pure tone audiometry. Evoked response audiometry found significant prolongation of absolute latencies of wave I, III, V, and wave I-III interpeak latency. Two cases with normal hearing had increased interpeak latencies. These findings constitute level 3b evidence. Findings were suggestive of retrocochlear pathology in two cases with normal hearing. In other patients, high frequency hearing loss may have led to altered evoked response results. Although scrub typhus appears to cause middle ear cochlear and retrocochlear damage, the presence of such damage could not be fully confirmed by evoked response audiometry.

  2. Characteristics and clinical applications of ocular vestibular evoked myogenic potentials.

    Science.gov (United States)

    Kantner, C; Gürkov, R

    2012-12-01

    Recently, ocular vestibular evoked myogenic potentials (oVEMPs) have been described and added to the neuro-otologic test battery as a new measure for the vestibulo-ocular reflex. oVEMPs represent extraocular muscle activity in response to otolith stimulation e.g. by air-conducted sound or bone-conducted vibration. In response to vestibular stimulation, electromyographic activity of the extraocular muscles can be recorded by means of surface electrodes placed beneath the contralateral eye. oVEMPs are likely to reflect predominantly utricular function, while the widely established cervical vestibular evoked myogenic potentials (cVEMPs) assess saccular function. Thus, measuring oVEMPs and cVEMPs in addition to caloric and head impulse testing provides further evaluation of the vestibular system and enables quick and cost-effective assessment of otolith function. This review summarizes the neurophysiological properties of oVEMPs, gives recommendations for recording conditions and discusses oVEMP alterations in various disorders of the vestibular system. With increasing insight into oVEMP characteristics in vestibular disorders, e.g. Menière's disease and superior semicircular canal dehiscence syndrome, oVEMPs are becoming a promising new diagnostic tool for evaluating utricular function. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Neonatal Masculinization Blocks Increased Excitatory Synaptic Input in Female Rat Nucleus Accumbens Core.

    Science.gov (United States)

    Cao, Jinyan; Dorris, David M; Meitzen, John

    2016-08-01

    Steroid sex hormones and genetic sex regulate the phenotypes of motivated behaviors and relevant disorders. Most studies seeking to elucidate the underlying neuroendocrine mechanisms have focused on how 17β-estradiol modulates the role of dopamine in striatal brain regions, which express membrane-associated estrogen receptors. Dopamine action is an important component of striatal function, but excitatory synaptic neurotransmission has also emerged as a key striatal substrate and target of estradiol action. Here, we focus on excitatory synaptic input onto medium spiny neurons (MSNs) in the striatal region nucleus accumbens core (AcbC). In adult AcbC, miniature excitatory postsynaptic current (mEPSC) frequency is increased in female compared with male MSNs. We tested whether increased mEPSC frequency in female MSNs exists before puberty, whether this increased excitability is due to the absence of estradiol or testosterone during the early developmental critical period, and whether it is accompanied by stable neuron intrinsic membrane properties. We found that mEPSC frequency is increased in female compared with male MSNs before puberty. Increased mEPSC frequency in female MSNs is abolished after neonatal estradiol or testosterone exposure. MSN intrinsic membrane properties did not differ by sex. These data indicate that neonatal masculinization via estradiol and/or testosterone action is sufficient for down-regulating excitatory synaptic input onto MSNs. We conclude that excitatory synaptic input onto AcbC MSNs is organized long before adulthood via steroid sex hormone action, providing new insight into a mechanism by which sex differences in motivated behavior and other AbcC functions may be generated or compromised.

  4. 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.

  5. Dynamic Excitatory and Inhibitory Gain Modulation Can Produce Flexible, Robust and Optimal Decision-making

    Science.gov (United States)

    Niyogi, Ritwik K.; Wong-Lin, KongFatt

    2013-01-01

    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 experimentally fitted

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

    Science.gov (United States)

    He, Zhimin; Cassaday, Helen J; Bonardi, Charlotte; Bibby, Peter A

    2013-01-01

    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 behavior - and thus its disruption could produce a correspondingly wide range of behavioral deficits. The present study employed a computer-based task to measure conditioned excitation and inhibition in the same discrimination procedure. CI 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 (1982) reinforcement sensitivity theory and Eysenck and Eysenck (1991) psychoticism, extraversion, and neuroticism theory. Following the behavioral tasks, participants completed the behavioral inhibition system/behavioral activation system (BIS/BAS) scales 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 behavioral activation and behavioral inhibition on excitatory and inhibitory learning respectively.

  7. Transient Evoked aotacoustic emissions otologically normal adults

    African Journals Online (AJOL)

    ABUTH

    Objective: To examine the effects of aging on the existence of transient evoked otoacoustic emissions in normal adult. Material and methods 40 ... wax or any middle ear pathology which might affect the recording at TEOAEs. After that, ... related to decreased hearing sensitivity and are independent of aging, Previous studies.

  8. Neural correlates of evoked phantom limb sensations.

    Science.gov (United States)

    Andoh, J; Diers, M; Milde, C; Frobel, C; Kleinböhl, D; Flor, H

    2017-05-01

    Previous work showed the existence of changes in the topographic organization within the somatosensory cortex (SI) in amputees with phantom limb pain, however, the link between nonpainful phantom sensations such as cramping or tingling or the percept of the limb and cortical changes is less clear. We used functional magnetic resonance imaging (fMRI) in a highly selective group of limb amputees who experienced inducible and reproducible nonpainful phantom sensations. A standardized procedure was used to locate body sites eliciting phantom sensations in each amputee. Selected body sites that could systematically evoke phantom sensations were stimulated using electrical pulses in order to induce phasic phantom sensations. Homologous body parts were also stimulated in a group of matched controls. Activations related to evoked phantom sensations were found bilaterally in SI and the intraparietal sulci (IPS), which significantly correlated with the intensity of evoked phantom sensations. In addition, we found differences in intra- and interhemispheric interaction between amputees and controls during evoked phantom sensations. We assume that phantom sensations might be associated with a functional decoupling between bilateral SI and IPS, possibly resulting from transcallosal reorganization mechanisms following amputation. Copyright © 2017. Published by Elsevier B.V.

  9. P2X7R modulation of visually evoked synaptic responses in the retina.

    Science.gov (United States)

    Chavda, Seetal; Luthert, Philip J; Salt, Thomas E

    2016-12-01

    P2X7Rs are distributed throughout all layers of the retina, and thus, their localisation on various cell types puts into question their specific site(s) of action. Using a dark-adapted, ex vivo mouse retinal whole mount preparation, the present study aimed to characterise the effect of P2X7R activation on light-evoked, excitatory RGC ON-field excitatory post-synaptic potentials (fEPSPs) and on outer retinal electroretinogram (ERG) responses under comparable conditions. The pharmacologically isolated NMDA receptor-mediated RGC ON-fEPSP was reduced in the presence of BzATP, an effect which was significantly attenuated by A438079 and other selective P2X7R antagonists A804598 or AF27139. In physiological Krebs medium, BzATP induced a significant potentiation of the ERG a-wave, with a concomitant reduction in the b-wave and the power of the oscillatory potentials. Conversely, in the pharmacologically modified Mg2+-free perfusate, BzATP reduced both the a-wave and b-wave. The effects of BzATP on the ERG components were suppressed by A438079. A role for P2X7R function in visual processing in both the inner and outer retina under physiological conditions remains controversial. The ON-fEPSP was significantly reduced in the presence of A804598 but not by A438079 or AF27139. Furthermore, A438079 did not have any effect on the ERG components in physiological Krebs but potentiated and reduced the a-wave and b-wave, respectively, when applied to the pharmacologically modified medium. Therefore, activation of P2X7Rs affects the function in the retinal ON pathway. The presence of a high concentration of extracellular ATP would most likely contribute to the modulation of visual transmission in the retina in the pathophysiological microenvironment.

  10. Low doses of urethane effectively inhibit spinal seizures evoked by sudden cooling of toad isolated spinal cord

    Energy Technology Data Exchange (ETDEWEB)

    Pina-crespo, J.C.; Dalo, N.L. (Univ. Centroccidental Lisandro Alvarado, Barquisimeto (Venezuela))

    1992-01-01

    The effect of low doses of urethane on three phases of spinal seizures evoked by sudden cooling (SSSC) of toad isolated spinal cord was studied. In control toads, SSSC began with a latency of 91[plus minus]3 sec exhibiting brief tremors, followed by clonic muscle contractions and finally reaching a tonic contraction. The latency of onset of seizures was significantly enhanced. The tonic phase was markedly abolished in toads pretreated intralymphaticaly with 0.15 g/kg of urethane. Tremors were the only phase observed in 55% of toads that received doses of 0.2 g/kg, and a total blockage of seizures was seen after doses of 0.25 g/kg of urethane in 50% of the preparations. A possible depressant effect of urethane on transmission mediated by excitatory amino acids is suggested.

  11. 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.

  12. SYNGAP1 links the maturation rate of excitatory synapses to the duration of critical-period synaptic plasticity.

    Science.gov (United States)

    Clement, James P; Ozkan, Emin D; Aceti, Massimiliano; Miller, Courtney A; Rumbaugh, Gavin

    2013-06-19

    Critical periods of developmental plasticity contribute to the refinement of neural connections that broadly shape brain development. These windows of plasticity are thought to be important for the maturation of perception, language, and cognition. Synaptic properties in cortical regions that underlie critical periods influence the onset and duration of windows, although it remains unclear how mechanisms that shape synapse development alter critical-period properties. In this study, we demonstrate that inactivation of a single copy of syngap1, which causes a surprisingly common form of sporadic, non-syndromic intellectual disability with autism in humans, induced widespread early functional maturation of excitatory connections in the mouse neocortex. This accelerated functional maturation was observed across distinct areas and layers of neocortex and directly influenced the duration of a critical-period synaptic plasticity associated with experience-dependent refinement of cortical maps. These studies support the idea that genetic control over synapse maturation influences the duration of critical-period plasticity windows. These data also suggest that critical-period duration links synapse maturation rates to the development of intellectual ability.

  13. 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...

  14. Deletion of the amyloid precursor-like protein 1 (APLP1) enhances excitatory synaptic transmission, reduces network inhibition but does not impair synaptic plasticity in the mouse dentate gyrus.

    Science.gov (United States)

    Vnencak, Matej; Paul, Mandy H; Hick, Meike; Schwarzacher, Stephan W; Del Turco, Domenico; Müller, Ulrike C; Deller, Thomas; Jedlicka, Peter

    2015-08-01

    Amyloid precursor-like protein 1 (APLP1) is a transmembrane synaptic protein belonging to the amyloid precursor protein (APP) gene family. Although the role of this gene family-in particular of APP-has been intensely studied in the context of Alzheimer's disease, the physiological roles of its family members remain poorly understood. In particular, the function of APLP1, which is predominantly expressed in the nervous system, has remained enigmatic. Since APP has been implicated in synaptic plasticity, we wondered whether APLP1 could play a similar role. First, using in situ hybridization and laser microdissection combined with reverse transcription-quantitative polymerase chain reaction (PCR) we observed that Aplp1 mRNA is highly expressed in dentate granule cells. Having this examined, we studied synaptic plasticity at the perforant path-granule cell synapses in the dentate gyrus of APLP1-deficient mice in vivo. Analysis of field excitatory postsynaptic potentials evoked by stimulation of perforant path fibers revealed increased excitatory transmission in APLP1-deficient mice. Moreover, we observed decreased paired-pulse inhibition of population spikes indicating a decrease in network inhibition upon deletion of APLP1. In contrast, short-term presynaptic plasticity (STP) as well as long-term synaptic plasticity (LTP) was unchanged in the absence of APLP1. Based on these results we conclude that APLP1 deficiency on its own does not lead to defects in synaptic plasticity, but affects synaptic transmission and network inhibition in the dentate gyrus. © 2015 Wiley Periodicals, Inc.

  15. Wiener kernel analysis of a noise-evoked otoacoustic emission

    NARCIS (Netherlands)

    van Dijk, P; Maat, A; Wit, H P

    1997-01-01

    In one specimen of the frog species, Rana esculenta, the following were measured: (1) a spontaneous otoacoustic emission; (2) a click-evoked otoacoustic emissions; and (3) a noise evoked otoacoustic emission. From the noise evoked emission response, a first-and a second-order Wiener kernel and the

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Presynaptic LRP4 promotes synapse number and function of excitatory CNS neurons.

    Science.gov (United States)

    Mosca, Timothy J; Luginbuhl, David J; Wang, Irving E; Luo, Liqun

    2017-06-13

    Precise coordination of synaptic connections ensures proper information flow within circuits. The activity of presynaptic organizing molecules signaling to downstream pathways is essential for such coordination, though such entities remain incompletely known. We show that LRP4, a conserved transmembrane protein known for its postsynaptic roles, functions presynaptically as an organizing molecule. In the Drosophila brain, LRP4 localizes to the nerve terminals at or near active zones. Loss of presynaptic LRP4 reduces excitatory (not inhibitory) synapse number, impairs active zone architecture, and abolishes olfactory attraction - the latter of which can be suppressed by reducing presynaptic GABA B receptors. LRP4 overexpression increases synapse number in excitatory and inhibitory neurons, suggesting an instructive role and a common downstream synapse addition pathway. Mechanistically, LRP4 functions via the conserved kinase SRPK79D to ensure normal synapse number and behavior. This highlights a presynaptic function for LRP4, enabling deeper understanding of how synapse organization is coordinated.

  18. Specification of excitatory neurons in the developing cerebral cortex: progenitor diversity and environmental influences.

    Science.gov (United States)

    Costa, Marcos R; Müller, Ulrich

    2014-01-01

    The mature cerebral cortex harbors a heterogeneous population of glutamatergic neurons, organized into a highly intricate histological architecture. Classically, this mixed population of neurons was thought to be generated sequentially from a seemingly homogenous group of progenitors under the influence of external cues. This view, however, has been challenged in the last decade by evidences pointing to the existence of fate-restricted neuronal progenitors in the developing neocortex. Here, we review classical studies using cell transplantation, retroviral labeling and cell culture, as well as new data from genetic fate-mapping analysis, to discuss the lineage relationships between neocortical progenitors and subclasses of excitatory neurons. We also propose a temporal model to conciliate the existence of fate-restricted progenitors alongside multipotent progenitors in the neocortex. Finally, we discuss evidences for a critical period of plasticity among post mitotic excitatory cortical neurons when environmental influences could change neuronal cell fate.

  19. Tertiary Oximes on Brain Acetylcholinesterase and Central Excitatory Effects of Nerve Agents

    Science.gov (United States)

    2012-01-01

    3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE Tertiary Oximes on Brain Acetylcholinesterase and Central Excitatory Effects of Nerve 5a...pralidoxime (2-PAM) to reactivate inhibited AChE. The quaternary structure of this oxime does not allow it to cross the blood brain barrier (BBB) to...propan-1-aminium chloride (DHAP), two tertiary oximes that can penetrate the BBB, could prevent or reverse the central toxic effects of three nerve

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

    Science.gov (United States)

    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. Model-Free Reconstruction of Excitatory Neuronal Connectivity from Calcium Imaging Signals

    Science.gov (United States)

    Stetter, Olav; Battaglia, Demian; Soriano, Jordi; Geisel, Theo

    2012-01-01

    A systematic assessment of global neural network connectivity through direct electrophysiological assays has remained technically infeasible, even in simpler systems like dissociated neuronal cultures. We introduce an improved algorithmic approach based on Transfer Entropy to reconstruct structural connectivity from network activity monitored through calcium imaging. We focus in this study on the inference of excitatory synaptic links. Based on information theory, our method requires no prior assumptions on the statistics of neuronal firing and neuronal connections. The performance of our algorithm is benchmarked on surrogate time series of calcium fluorescence generated by the simulated dynamics of a network with known ground-truth topology. We find that the functional network topology revealed by Transfer Entropy depends qualitatively on the time-dependent dynamic state of the network (bursting or non-bursting). Thus by conditioning with respect to the global mean activity, we improve the performance of our method. This allows us to focus the analysis to specific dynamical regimes of the network in which the inferred functional connectivity is shaped by monosynaptic excitatory connections, rather than by collective synchrony. Our method can discriminate between actual causal influences between neurons and spurious non-causal correlations due to light scattering artifacts, which inherently affect the quality of fluorescence imaging. Compared to other reconstruction strategies such as cross-correlation or Granger Causality methods, our method based on improved Transfer Entropy is remarkably more accurate. In particular, it provides a good estimation of the excitatory network clustering coefficient, allowing for discrimination between weakly and strongly clustered topologies. Finally, we demonstrate the applicability of our method to analyses of real recordings of in vitro disinhibited cortical cultures where we suggest that excitatory connections are characterized

  2. Model-free reconstruction of excitatory neuronal connectivity from calcium imaging signals.

    Directory of Open Access Journals (Sweden)

    Olav Stetter

    Full Text Available A systematic assessment of global neural network connectivity through direct electrophysiological assays has remained technically infeasible, even in simpler systems like dissociated neuronal cultures. We introduce an improved algorithmic approach based on Transfer Entropy to reconstruct structural connectivity from network activity monitored through calcium imaging. We focus in this study on the inference of excitatory synaptic links. Based on information theory, our method requires no prior assumptions on the statistics of neuronal firing and neuronal connections. The performance of our algorithm is benchmarked on surrogate time series of calcium fluorescence generated by the simulated dynamics of a network with known ground-truth topology. We find that the functional network topology revealed by Transfer Entropy depends qualitatively on the time-dependent dynamic state of the network (bursting or non-bursting. Thus by conditioning with respect to the global mean activity, we improve the performance of our method. This allows us to focus the analysis to specific dynamical regimes of the network in which the inferred functional connectivity is shaped by monosynaptic excitatory connections, rather than by collective synchrony. Our method can discriminate between actual causal influences between neurons and spurious non-causal correlations due to light scattering artifacts, which inherently affect the quality of fluorescence imaging. Compared to other reconstruction strategies such as cross-correlation or Granger Causality methods, our method based on improved Transfer Entropy is remarkably more accurate. In particular, it provides a good estimation of the excitatory network clustering coefficient, allowing for discrimination between weakly and strongly clustered topologies. Finally, we demonstrate the applicability of our method to analyses of real recordings of in vitro disinhibited cortical cultures where we suggest that excitatory connections

  3. Unsupervised Discrimination of Patterns in Spiking Neural Networks with Excitatory and Inhibitory Synaptic Plasticity

    Directory of Open Access Journals (Sweden)

    Narayan eSrinivasa

    2014-12-01

    Full Text Available 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.

  4. 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’,...

  5. 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.

  6. Cannabinoid CB1 receptor signaling dichotomously modulates inhibitory and excitatory synaptic transmission in rat inner retina.

    Science.gov (United States)

    Wang, Xiao-Han; Wu, Yi; Yang, Xiao-Fang; Miao, Yanying; Zhang, Chuan-Qiang; Dong, Ling-Dan; Yang, Xiong-Li; Wang, Zhongfeng

    2016-01-01

    In the inner retina, ganglion cells (RGCs) integrate and process excitatory signal from bipolar cells (BCs) and inhibitory signal from amacrine cells (ACs). Using multiple labeling immunohistochemistry, we first revealed the expression of the cannabinoid CB1 receptor (CB1R) at the terminals of ACs and BCs in rat retina. By patch-clamp techniques, we then showed how the activation of this receptor dichotomously regulated miniature inhibitory postsynaptic currents (mIPSCs), mediated by GABAA receptors and glycine receptors, and miniature excitatory postsynaptic currents (mEPSCs), mediated by AMPA receptors, of RGCs in rat retinal slices. WIN55212-2 (WIN), a CB1R agonist, reduced the mIPSC frequency due to an inhibition of L-type Ca(2+) channels no matter whether AMPA receptors were blocked. In contrast, WIN reduced the mEPSC frequency by suppressing T-type Ca(2+) channels only when inhibitory inputs to RGCs were present, which could be in part due to less T-type Ca(2+) channels of cone BCs, presynaptic to RGCs, being in an inactivation state under such condition. This unique feature of CB1R-mediated retrograde regulation provides a novel mechanism for modulating excitatory synaptic transmission in the inner retina. Moreover, depolarization of RGCs suppressed mIPSCs of these cells, an effect that was eliminated by the CB1R antagonist SR141716, suggesting that endocannabinoid is indeed released from RGCs.

  7. The columnar and laminar organization of inhibitory connections to neocortical excitatory cells.

    Science.gov (United States)

    Kätzel, Dennis; Zemelman, Boris V; Buetfering, Christina; Wölfel, Markus; Miesenböck, Gero

    2011-01-01

    The cytoarchitectonic similarities of different neocortical regions have given rise to the idea of 'canonical' connectivity between excitatory neurons of different layers within a column. It is unclear whether similarly general organizational principles also exist for inhibitory neocortical circuits. Here we delineate and compare local inhibitory-to-excitatory wiring patterns in all principal layers of primary motor (M1), somatosensory (S1) and visual (V1) cortex, using genetically targeted photostimulation in a mouse knock-in line that conditionally expresses channelrhodopsin-2 in GABAergic neurons. Inhibitory inputs to excitatory neurons derived largely from the same cortical layer within a three-column diameter. However, subsets of pyramidal cells in layers 2/3 and 5B received extensive translaminar inhibition. These neurons were prominent in V1, where they might correspond to complex cells, less numerous in barrel cortex and absent in M1. Although inhibitory connection patterns were stereotypical, the abundance of individual motifs varied between regions and cells, potentially reflecting functional specializations.

  8. The amygdala excitatory/inhibitory balance in a valproate-induced rat autism model.

    Directory of Open Access Journals (Sweden)

    Hui-Ching Lin

    Full Text Available The amygdala is an important structure contributing to socio-emotional behavior. However, the role of the amygdala in autism remains inconclusive. In this study, we used the 28-35 days valproate (VPA-induced rat model of autism to observe the autistic phenotypes and evaluate their synaptic characteristics in the lateral nucleus (LA of the amygdala. The VPA-treated offspring demonstrated less social interaction, increased anxiety, enhanced fear learning and impaired fear memory extinction. Slice preparation and electrophysiological recordings of the amygdala showed significantly enhanced long-term potentiation (LTP while stimulating the thalamic-amygdala pathway of the LA. In addition, the pair pulse facilitation (PPF at 30- and 60-ms intervals decreased significantly. Whole-cell recordings of the LA pyramidal neurons showed an increased miniature excitatory postsynaptic current (EPSC frequency and amplitude. The relative contributions of the AMPA receptor and NMDA receptor to the EPSCs did not differ significantly between groups. These results suggested that the enhancement of the presynaptic efficiency of excitatory synaptic transmission might be associated with hyperexcitibility and enhanced LTP in LA pyramidal neurons. Disruption of the synaptic excitatory/inhibitory (E/I balance in the LA of VPA-treated rats might play certain roles in the development of behaviors in the rat that may be relevant to autism. Further experiments to demonstrate the direct link are warranted.

  9. Alterations of functional properties of hippocampal networks following repetitive closed-head injury.

    Science.gov (United States)

    Logue, Omar C; Cramer, Nathan P; Xu, Xiufen; Perl, Daniel P; Galdzicki, Zygmunt

    2016-03-01

    Traumatic brain injury (TBI) is the leading cause of death for persons under the age of 45. Military service members who have served on multiple combat deployments and contact-sport athletes are at particular risk of sustaining repetitive TBI (rTBI). Cognitive and behavioral deficits resulting from rTBI are well documented. Optimal associative LTP, occurring in the CA1 hippocampal Schaffer collateral pathway, is required for both memory formation and retrieval. Surprisingly, ipsilateral Schaffer collateral CA1 LTP evoked by 100 Hz tetanus was enhanced in mice from the 3× closed head injury (3× CHI) treatment group in comparison to LTP in contralateral or 3× Sham CA1 area, and in spite of reduced freezing during contextual fear conditioning at one week following 3× CHI. Electrophysiological activity of CA1 neurons was evaluated with whole-cell patch-clamp recordings. 3× CHI ipsilateral CA1 neurons exhibited significant increases in action potential amplitude and maximum rise and decay slope while the action potential duration was decreased. Recordings of CA1 neuron postsynaptic currents were conducted to detect spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs/sIPSCs) and respective miniature currents (mEPSCs and mIPSCs). In the 3× CHI mice, sEPSCs and sIPSCs in ipsilateral CA1 neurons had an increased frequency of events but decreased amplitudes. In addition, 3× CHI altered the action potential-independent miniature postsynaptic currents. The mEPSCs of ipsilateral CA1 neurons exhibited both an increased frequency of events and larger amplitudes. Moreover, the effect of 3× CHI on mIPSCs was opposite to that of the sIPSCs. Specifically, the frequency of the mIPSCs was decreased while the amplitudes were increased. These results are consistent with a mechanism in which repetitive closed-head injury affects CA1 hippocampal function by promoting a remodeling of excitatory and inhibitory synaptic inputs leading to impairment in hippocampal

  10. 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.

  11. Do establishing operations alter reinforcement effectiveness?

    OpenAIRE

    Cherpas, Chris

    1993-01-01

    Michael (this issue) defines an establishing operation (EO), such as food deprivation, as (a) altering the effectiveness of reinforcement as well as (b) evoking behavior. Although this dual role for EOs is compelling, it is possible that such operations have only evocative effects (i.e., function only in the form of antecedent control). The main question raised here is how the reinforcement-altering function can be experimentally analyzed. Evolutionary and conceptual implications of the two-f...

  12. Do establishing operations alter reinforcement effectiveness?

    Science.gov (United States)

    Cherpas, C

    1993-01-01

    Michael (this issue) defines an establishing operation (EO), such as food deprivation, as (a) altering the effectiveness of reinforcement as well as (b) evoking behavior. Although this dual role for EOs is compelling, it is possible that such operations have only evocative effects (i.e., function only in the form of antecedent control). The main question raised here is how the reinforcement-altering function can be experimentally analyzed. Evolutionary and conceptual implications of the two-function EO are also considered.

  13. Spatiotemporal Patterns of an Evoked Network Oscillation in Neocortical Slices: Coupled Local Oscillators

    Science.gov (United States)

    Bai, Li; Huang, Xiaoying; Yang, Qian; Wu, Jian-young

    2015-01-01

    We have discovered an evoked network oscillation in rat neocortical slices and have examined its spatiotemporal patterns with voltage sensitive dye imaging. The slices (visual and auditory cortices) were prepared in a medium of low calcium, high magnesium and with sodium replaced by choline in order to reduce the excito-toxicity and sodium loading. After slicing, the choline was washed out while normal calcium, magnesium and sodium concentrations were restored. The oscillation was evoked by a single electrical shock to slices bathed in normal artificial cerebral spinal fluid (ACSF). The oscillation was organized as an all-or-none epoch containing 4 to 13 cycles at a central frequency around 25 Hz. The activity can be reversibly blocked by CNQX, APV and atropine, but not by bicuculline, indicating poly-synaptic excitatory mechanisms. Voltage sensitive dye imaging showed high amplitude oscillation signals in superficial and middle cortical layers. Spatiotemporally, the oscillations were organized as waves, propagating horizontally along cortical laminar. Each oscillation cycle was associated with one wave propagating in space. The waveforms were often different at different locations (e.g., extra cycles), suggesting the co-existence of multiple local oscillators. For different cycles, the waves often initiated at different locations, suggesting that local oscillators are competing to initiate each oscillation cycle. Overall our results suggest that this cortical network oscillation is organized at two levels: locally, oscillating neurons are tightly coupled to form local oscillators, and globally the coupling between local oscillators is weak, allowing abrupt spatial phase lags and propagating waves with multiple initiation sites. PMID:16870836

  14. The Princip cult and what it evokes in Hungary

    Directory of Open Access Journals (Sweden)

    Eric Beckett Weaver

    2016-08-01

    Full Text Available The Princip cult and what it evokes in Hungary On the 28th of June, 1914, a consumptive student, Gavrilo Princip, shot and killed prince Franz Ferdinand, the heir to the throne of the Austro-Hungarian Monarchy. The prince’s wife Sofia was also killed by a stray bullet. In the century that has passed since the assassination, the memory of Princip and the cult constructed around him has been distorted beyond recognition. As local and international politics were altered, so changed Princip’s image. The memory of Princip now evokes strong reactions not only in the South Slav lands, but in Hungary as well. In what follows, we will examine possible sources for the strong reactions evoked by Princip’s memory among Hungarians a century after his act.   Kult Principa i co on ewokuje na Węgrzech W dniu 28 czerwca 1914 roku chory na gruźlicę student Gavrilo Princip zastrzelił księcia Franciszka Ferdynanda, następcę tronu monarchii austro-węgierskiej. Od zbłąkanej kuli zginęła także żona księcia, Zofia. W okresie stulecia, które minęło od tego zabójstwa, pamięć o Principie i kult zbudowany wokół niego przeobraziły się diametralnie. Wraz z przemianami polityki lokalnej i międzynarodowej zmieniało się także postrzeganie Principa. Obecnie pamięć o Principie wywołuje silne reakcje nie tylko na ziemiach południowosłowiańskich, ale również na Węgrzech. Autor artykułu docieka, skąd mogą wypływać silne reakcje, jakie pamięć Principa wywołuje u Węgrów sto lat po jego czynie.

  15. Light-evoked S-nitrosylation in the retina

    Science.gov (United States)

    Tooker, Ryan E; Vigh, Jozsef

    2015-01-01

    Nitric oxide (NO) synthesis in the retina is triggered by light stimulation. NO has been shown to modulate visual signal processing at multiple sites in the vertebrate retina, via activation of the most sensitive target of NO signaling, soluble guanylate cyclase. NO can also alter protein structure and function and exert biological effects directly by binding to free thiol groups of cysteine residues in a chemical reaction called S-nitrosylation. However, in the central nervous system, including the retina, this reaction has not been considered to be significant under physiological conditions. Here we provide immunohistochemical evidence for extensive S-nitrosylation that takes place in the goldfish and mouse retinas under physiologically relevant light intensities, in an intensity-dependent manner, with a strikingly similar pattern in both species. Pre-treatment with NEM, which occludes S-nitrosylation, or with TRIM, an inhibitor of neuronal NO synthase, eliminated the light-evoked increase in S-nitrosylated protein immunofluorescence (SNI) in the retinas of both species. Similarly, light did not increase SNI, above basal levels, in retinas of transgenic mice lacking neuronal NO synthase. Qualitative analysis of the light-adapted mouse retina with mass spectrometry revealed more than 300 proteins that were S-nitrosylated upon illumination, many of which are known to participate directly in retinal signal processing. Our data strongly suggest that in the retina, light-evoked NO production leads to extensive S-nitrosylation and that this process is a significant post-translational modification affecting a wide range of proteins under physiological conditions. PMID:25823749

  16. EFFECT OF SMOKING ON TRASIENTLY EVOKED OTOACOUSTIC EMISSION.

    Science.gov (United States)

    Gegenava, Kh; Japaridze, Sh; Sharashenidze, N; Jalabadze, G; Kevanishvili, Z

    2016-01-01

    Evoked otoacoustic emissions, EOAEs, are proved to be sounds aroused in response to external acoustic stimulus by the cochlear outer hair cells. Transiently evoked otoacoustic emissions, TEOAEs, are the most clinically utilized EOAEs. TEOAEs are detectable in 98% of people with normal hearing, regardless of age or sex, while two ears of any individual produce similar TEOAEs waveforms. The objective of the presented study was the comparison of TEOAE magnitudes in cigarette smokers and nonsmokers. The TEOAE occurrence and characteristics in individuals of both samples with audiometrically proved hearing losses and in those without were also specifically examined. 30 smokers and and 30 nonsmokers within the age range of 30-59 years were involved in the present study after informed concent. OAEs were performed to each subject by Madsen Capella's-OAE/middle ear analyzer-GN Otometrics, (Danmark). After OAE testing each subject was performed routine pure-tone audiometry and tympanometry. Obtained results were statistically treated by the student's t-distribution. According to our results 76.6% of smokers and 3.33% of nonsmokers had marked different level decrease in TEOAE amplitude. Audiographic measurments showed altered audiogram in 6.7% of smokers and in 3.33% of nonsmokers. Based on the above mentioned results we suppose that smoking has significant influence on hearing function, especially on cochlear apparatus; At the same time, TOEAE, as a sensitive method can be used for very early detection of hearing loss, even when there are neither any subjective complains nor some changies on audiogram.

  17. Light-evoked S-nitrosylation in the retina.

    Science.gov (United States)

    Tooker, Ryan E; Vigh, Jozsef

    2015-10-01

    Nitric oxide (NO) synthesis in the retina is triggered by light stimulation. NO has been shown to modulate visual signal processing at multiple sites in the vertebrate retina, via activation of the most sensitive target of NO signaling, soluble guanylate cyclase. NO can also alter protein structure and function and exert biological effects directly by binding to free thiol groups of cysteine residues in a chemical reaction called S-nitrosylation. However, in the central nervous system, including the retina, this reaction has not been considered to be significant under physiological conditions. Here we provide immunohistochemical evidence for extensive S-nitrosylation that takes place in the goldfish and mouse retinas under physiologically relevant light intensities, in an intensity-dependent manner, with a strikingly similar pattern in both species. Pretreatment with N-ethylmaleimide (NEM), which occludes S-nitrosylation, or with 1-(2-trifluromethylphenyl)imidazole (TRIM), an inhibitor of neuronal NO synthase, eliminated the light-evoked increase in S-nitrosylated protein immunofluorescence (SNI) in the retinas of both species. Similarly, light did not increase SNI, above basal levels, in retinas of transgenic mice lacking neuronal NO synthase. Qualitative analysis of the light-adapted mouse retina with mass spectrometry revealed more than 300 proteins that were S-nitrosylated upon illumination, many of which are known to participate directly in retinal signal processing. Our data strongly suggest that in the retina light-evoked NO production leads to extensive S-nitrosylation and that this process is a significant posttranslational modification affecting a wide range of proteins under physiological conditions. © 2015 Wiley Periodicals, Inc.

  18. Influence of rotating shift work on visual reaction time and visual evoked potential.

    Science.gov (United States)

    R V, Hemamalini; N, Krishnamurthy; A, Saravanan

    2014-10-01

    The present day life style is changing the circadian rhythm of the body especially in rotating night shift workers. The impact of this prolongs their reaction time. Night shift also interferes with the circadian variation of pupil size which may affect the visual evoked potential. To compare the visual reaction time, visual evoked potential (VEP) in rotating night shift workers & day workers and also to correlate the changes in visual reaction time with visual evoked potential. Forty healthy male security guards & staff (25 - 35 y) who did rotating night shifts at least for six months & 40 d workers (25 - 35 y) who did not do night shift in last two years were involved in the study. Visual reaction time and the latency & amplitude of VEP were recorded. Kolmogorov- Smirnov test for normalcy showed the latencies & amplitude of VEP to be normally distributed. Student's unpaired t test showed significant difference (ptime and in the latencies of VEP between night shift & day workers. There was no significant difference in the amplitude of VEP. Night shift workers who are prone to circadian rhythm alteration will have prolonged visual reaction time & visual evoked potential abnormalities. Implementation of Bright Light Therapy would be beneficial to the night shift worker.

  19. Long-term moderate exercise accelerates the recovery of stress-evoked cardiovascular responses.

    Science.gov (United States)

    Hsu, Yuan-Chang; Tsai, Sheng-Feng; Yu, Lung; Chuang, Jih-Ing; Wu, Fong-Sen; Jen, Chauying J; Kuo, Yu-Min

    2016-01-01

    Psychological stress is an important global health problem. It is well documented that stress increases the incidences of various cardiovascular disorders. Regular exercise is known to reduce resting blood pressure (BP) and heart rate (HR). This study was designed to clarify the effects of long-term exercise on stress-evoked cardiovascular responses and to emphasize post-stress recovery effects. Male Wistar rats underwent 8 weeks of moderate treadmill training, with cardiovascular responses, autonomic nervous system activities and local Fos reactivity changes in the cardiovascular regulation center were monitored before, during and after immobilization stress. A spectral analysis of cardiovascular parameters was used to examine autonomic nervous activities. We found that long-term exercise (i) lowered resting BP, HR and sympathetic activity, but increased resting parasympathetic activity and baroreflex sensitivity (BRS); (ii) accelerated post-stress recovery of stress-evoked cardiovascular and sympathetic responses along with increased BRS and (iii) accelerated post-stress recovery of stress-evoked neuron activations in the paraventricular nucleus, but delayed it in the nucleus of the tractus solitarius. We conclude that, in rats, long-term exercise accelerated recovery of stress-evoked cardiovascular responses differentially altering hypothalamic and medullar neuron activities.

  20. 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.

  1. Music-Evoked Emotions—Current Studies

    Directory of Open Access Journals (Sweden)

    Hans-Eckhardt Schaefer

    2017-11-01

    Full Text Available 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.

  2. 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

  3. Do ambient urban odors evoke basic emotions?

    Directory of Open Access Journals (Sweden)

    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.

  4. Somatosensory evoked response: application in neurology

    Directory of Open Access Journals (Sweden)

    Carlos A. M. Guerreiro

    1982-03-01

    Full Text Available One technique used for short-latency somatosensory evoked response (SER is described. SER following nerve stimulation is a unique non-invasive, clinical test used to evaluate the somatosensory pathways. It tests the physiological function of the median nerve, the brachial plexus, the C6-7 cervical roots, cervical spinal cord, the cuneate nuclei, the medial lemniscus, the thalamus, and the contralateral sensory cortex. It has been shown to be a reliable and useful clinical test partiicularly in multiple sclerosis and comatose patients. The promising technique of SER following peroneal nerve stimulation is mentioned.

  5. Differential effects of LSD serotonin and l-tryptophan on visually evoked responses.

    Science.gov (United States)

    Strahlendorf, J C; Goldstein, F J; Rossi, G V; Malseed, R T

    1982-01-01

    Alterations in photically-evoked cortical responses were assessed in immobilized artificially respired cats following intraraphe microinjections of LSD and serotonin (5-HT) and IV administration of LSD and l-tryptophan. Both systemic (10-100 micrograms/kg; N = 5) and intraraphe (0.25 microgram; N = 10) LSD significantly increased the amplitudes of the three primary components of the visual evoked response (VER). In contrast, the same VER components were significantly depressed following intraraphe 5-HT (30 micrograms; N = 4) and IV l-tryptophan (100 mg/kg; N = 6), a serotonin precursor that elevates raphe 5-HT levels. Intraraphe cinanserin (180 micrograms; 30 minute pretreatment) completely reversed LSD-induced enhancements in all three components (p less than 0.01). Depressions of VER following intraraphe 5-HT (30 micrograms) were also antagonized by cinanserin, although to lesser degree (p less than 0.05 for first 2 components only) than with LSD. The depressive effects of l-tryptophan (100 mg/kg) were unaffected by cinanserin. Modification of raphe neuronal activity can significantly alter photically evoked responses, and may explain the perceptual disturbances associated with LSD, i.e., depression of an area (raphe) normally inhibiting forebrain areas of the visual system.

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

    Directory of Open Access Journals (Sweden)

    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

  7. Enhancement by citral of glutamatergic spontaneous excitatory transmission in adult rat substantia gelatinosa neurons.

    Science.gov (United States)

    Zhu, Lan; Fujita, Tsugumi; Jiang, Chang-Yu; Kumamoto, Eiichi

    2016-02-10

    Although citral, which is abundantly present in lemongrass, has various actions including antinociception, how citral affects synaptic transmission has not been examined as yet. Citral activates in heterologous cells transient receptor potential vanilloid-1, ankyrin-1, and melastatin-8 (TRPV1, TRPA1, and TRPM8, respectively) channels, the activation of which in the spinal lamina II [substantia gelatinosa (SG)] increases the spontaneous release of L-glutamate from nerve terminals. It remains to be examined what types of transient receptor potential channel in native neurons are activated by citral. With a focus on transient receptor potential activation, we examined the effect of citral on glutamatergic spontaneous excitatory transmission using the whole-cell patch-clamp technique to SG neurons in adult rat spinal cord slices. Bath-applied citral for 3 min increased the frequency of spontaneous excitatory postsynaptic current in a concentration-dependent manner (half-maximal effective concentration=0.58 mM), with a small increase in its amplitude. The spontaneous excitatory postsynaptic current frequency increase produced by citral was repeated at a time interval of 30 min, albeit this action recovered with a slow time course after washout. The presynaptic effect of citral was inhibited by TRPA1 antagonist HC-030031, but not by voltage-gated Na-channel blocker tetrodotoxin, TRPV1 antagonist capsazepine, and TRPM8 antagonist BCTC. It is concluded that citral increases spontaneous L-glutamate release in SG neurons by activating TRPA1 channels. Considering that the SG plays a pivotal role in modulating nociceptive transmission from the periphery, the citral activity could contribute toward at least a part of the modulation.

  8. 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

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

    OpenAIRE

    Keith P. Johnson; Lei Zhao; Daniel Kerschensteiner

    2018-01-01

    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 ...

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

    Science.gov (United States)

    Shapiro-Reznik, Mika; Jilg, Anje; Lerner, Hadas; Earnest, David J; Zisapel, Nava

    2012-01-01

    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 scaffolding proteins

  11. [Personality dimensions and cerebral evoked potential].

    Science.gov (United States)

    Camposano, S; Alvarez, C; Lolas, F

    1994-12-01

    Eysenck's personality theory postulates 3 orthogonal dimensions of personality: extraversion (E), neuroticism (N) and psychoticism (P), predicting conductual and physiological predispositions to suffer mental illness. Biological bases of Eysenck's personality traits have been documented electrophysiologically. Psychoticism, the latest described dimension, is controverted, since there is some evidence of common factors with the other two. In order to assess the relation between Eysenck's dimensions and sensorial reactivity and information encoding processes we studied 20 healthy young subjects (mean age 28.5 years) with flash visual cortical evoked potentials (VEP, 3 intensities, peak to peak amplitude of III, IV-V-VI, VII components), and auditory cognitive evoked potentials (odd ball paradigm, P300 latency). There was a positive correlation between N and P dimensions (Spearman, r = 0.52), between N and VEP amplitude at high intensity (r = 0.58) and a negative correlation between E and P300 latency (r = 0.58). In short we found that P is not an independent dimension, but is related to sensorial reactivity. E dimension was related to encoding processes supporting Eysenck's observations about memory and learning differences.

  12. Long Latency Auditory Evoked Potentials during Meditation.

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    Telles, Shirley; Deepeshwar, Singh; Naveen, Kalkuni Visweswaraiah; Pailoor, Subramanya

    2015-10-01

    The auditory sensory pathway has been studied in meditators, using midlatency and short latency auditory evoked potentials. The present study evaluated long latency auditory evoked potentials (LLAEPs) during meditation. Sixty male participants, aged between 18 and 31 years (group mean±SD, 20.5±3.8 years), were assessed in 4 mental states based on descriptions in the traditional texts. They were (a) random thinking, (b) nonmeditative focusing, (c) meditative focusing, and (d) meditation. The order of the sessions was randomly assigned. The LLAEP components studied were P1 (40-60 ms), N1 (75-115 ms), P2 (120-180 ms), and N2 (180-280 ms). For each component, the peak amplitude and peak latency were measured from the prestimulus baseline. There was significant decrease in the peak latency of the P2 component during and after meditation (Pmeditation facilitates the processing of information in the auditory association cortex, whereas the number of neurons recruited was smaller in random thinking and non-meditative focused thinking, at the level of the secondary auditory cortex, auditory association cortex and anterior cingulate cortex. © EEG and Clinical Neuroscience Society (ECNS) 2014.

  13. Speech Evoked Auditory Brainstem Response in Stuttering

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    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.

  14. Glucagon-like peptide-2 modulates neurally evoked mucosal chloride secretion in guinea pig small intestine in vitro.

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    Baldassano, Sara; Liu, Sumei; Qu, Mei-Hu; Mulè, Flavia; Wood, Jackie D

    2009-10-01

    Glucagon-like peptide-2 (GLP-2) is an important neuroendocrine peptide in intestinal physiology. It influences digestion, absorption, epithelial growth, motility, and blood flow. We studied involvement of GLP-2 in intestinal mucosal secretory behavior. Submucosal-mucosal preparations from guinea pig ileum were mounted in Ussing chambers for measurement of short-circuit current (I(sc)) as a surrogate for chloride secretion. GLP-2 action on neuronal release of acetylcholine was determined with ELISA. Enteric neuronal expression of the GLP-2 receptor (GLP-2R) was studied with immunohistochemical methods. Application of GLP-2 (0.1-100 nM) to the serosal or mucosal side of the preparations evoked no change in baseline I(sc) and did not alter transepithelial ionic conductance. Transmural electrical field stimulation (EFS) evoked characteristic biphasic increases in I(sc), with an initially rapid rising phase followed by a sustained phase. Application of GLP-2 reduced the EFS-evoked biphasic responses in a concentration-dependent manner. The GLP-2R antagonist GLP-2-(3-33) significantly reversed suppression of the EFS-evoked responses by GLP-2. Tetrodotoxin, scopolamine, and hexamethonium, but not vasoactive intestinal peptide type 1 receptor (VPAC1) antagonist abolished or reduced to near zero the EFS-evoked responses. GLP-2 suppressed EFS-evoked acetylcholine release as measured by ELISA. Pretreatment with GLP-2-(3-33) offset this action of GLP-2. In the submucosal plexus, GLP-2R immunoreactivity (-IR) was expressed in choline acetyltransferase-IR neurons, somatostatin-IR neurons, neuropeptide Y-IR neurons, and vasoactive intestinal peptide-IR neurons. We conclude that submucosal neurons in the guinea pig ileum express GLP-2R. Activation of GLP-2R decreases neuronally evoked epithelial chloride secretion by suppressing acetylcholine release from secretomotor neurons.

  15. Excitatory and inhibitory effects of opiates in the rat vas deferens: a dual mechanism of opiate action.

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    Jacquet, Y F

    1980-10-03

    Both natural (-)-morphine and its unnatural enantiomer (+)-morphine exert an excitatory action on electrically stimulated contractions of rat vas deferens. Preexposure to (-)-morphine results in cross-tolerance to the inhibitory action of beta-endorphin. (-)-Naloxone and its stereoisomer (+)-naloxone also exert an excitatory action, but only (-)-naloxone bocks the inhibtory action of beta-endorphin. Thus morphine exerts a dual action on a peripheral organ: one an inhibitory action mediated by the stereospecific endorphin receptor that is blocked stereospecifically by naloxone, the other an excitatory action mediated by a nonstereospecific receptor that is not blocked by naloxone. The opiate abstinence syndrome is seen as due to the unmasking of the excitatory action of opiates when its concomitant inhibitory influence is removed by selective blockade by naloxone or weakened by selective tolerance. The view that the rat vas deferens is devoid of morphine receptors is now seen as arising from a reverse example of morphine's dual action: the masking of the inhibitory action of morphine by its concomitant and more potent excitatory action.

  16. Excitatory repetitive transcranial magnetic stimulation to left dorsal premotor cortex enhances motor consolidation of new skills

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    Boyd Lara A

    2009-07-01

    Full Text Available Abstract Background Following practice of skilled movements, changes continue to take place in the brain that both strengthen and modify memory for motor learning. These changes represent motor memory consolidation a process whereby new memories are transformed from a fragile to a more permanent, robust and stable state. In the present study, the neural correlates of motor memory consolidation were probed using repetitive transcranial magnetic stimulation (rTMS to the dorsal premotor cortex (PMd. Participants engaged in four days of continuous tracking practice that immediately followed either excitatory 5 HZ, inhibitory 1 HZ or control, sham rTMS. A delayed retention test assessed motor learning of repeated and random sequences of continuous movement; no rTMS was applied at retention. Results We discovered that 5 HZ excitatory rTMS to PMd stimulated motor memory consolidation as evidenced by off-line learning, whereas only memory stabilization was noted following 1 Hz inhibitory or sham stimulation. Conclusion Our data support the hypothesis that PMd is important for continuous motor learning, specifically via off-line consolidation of learned motor behaviors.

  17. The Balance of Excitatory and Inhibitory Synaptic Inputs for Coding Sound Location

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    Ono, Munenori

    2014-01-01

    The localization of high-frequency sounds in the horizontal plane uses an interaural-level difference (ILD) cue, yet little is known about the synaptic mechanisms that underlie processing this cue in the inferior colliculus (IC) of mouse. Here, we study the synaptic currents that process ILD in vivo and use stimuli in which ILD varies around a constant average binaural level (ABL) to approximate sounds on the horizontal plane. Monaural stimulation in either ear produced EPSCs and IPSCs in most neurons. The temporal properties of monaural responses were well matched, suggesting connected functional zones with matched inputs. The EPSCs had three patterns in response to ABL stimuli, preference for the sound field with the highest level stimulus: (1) contralateral; (2) bilateral highly lateralized; or (3) at the center near 0 ILD. EPSCs and IPSCs were well correlated except in center-preferred neurons. Summation of the monaural EPSCs predicted the binaural excitatory response but less well than the summation of monaural IPSCs. Binaural EPSCs often showed a nonlinearity that strengthened the response to specific ILDs. Extracellular spike and intracellular current recordings from the same neuron showed that the ILD tuning of the spikes was sharper than that of the EPSCs. Thus, in the IC, balanced excitatory and inhibitory inputs may be a general feature of synaptic coding for many types of sound processing. PMID:24599475

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

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    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.

  19. Asymmetric excitatory synaptic dynamics underlie interaural time difference processing in the auditory system.

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    Pablo E Jercog

    2010-06-01

    Full Text Available Low-frequency sound localization depends on the neural computation of interaural time differences (ITD and relies on neurons in the auditory brain stem that integrate synaptic inputs delivered by the ipsi- and contralateral auditory pathways that start at the two ears. The first auditory neurons that respond selectively to ITD are found in the medial superior olivary nucleus (MSO. We identified a new mechanism for ITD coding using a brain slice preparation that preserves the binaural inputs to the MSO. There was an internal latency difference for the two excitatory pathways that would, if left uncompensated, position the ITD response function too far outside the physiological range to be useful for estimating ITD. We demonstrate, and support using a biophysically based computational model, that a bilateral asymmetry in excitatory post-synaptic potential (EPSP slopes provides a robust compensatory delay mechanism due to differential activation of low threshold potassium conductance on these inputs and permits MSO neurons to encode physiological ITDs. We suggest, more generally, that the dependence of spike probability on rate of depolarization, as in these auditory neurons, provides a mechanism for temporal order discrimination between EPSPs.

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

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    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

  1. Layer-Specific Organization of Local Excitatory and Inhibitory Synaptic Connectivity in the Rat Presubiculum

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    Peng, Yangfan; Barreda Tomás, Federico J.; Klisch, Constantin; Vida, Imre

    2017-01-01

    Abstract The presubiculum is part of the parahippocampal spatial navigation system and contains head direction and grid cells upstream of the medial entorhinal cortex. This position within the parahippocampal cortex renders the presubiculum uniquely suited for analyzing the circuit requirements underlying the emergence of spatially tuned neuronal activity. To identify the local circuit properties, we analyzed the topology of synaptic connections between pyramidal cells and interneurons in all layers of the presubiculum by testing 4250 potential synaptic connections using multiple whole-cell recordings of up to 8 cells simultaneously. Network topology showed layer-specific organization of microcircuits consistent with the prevailing distinction of superficial and deep layers. While connections among pyramidal cells were almost absent in superficial layers, deep layers exhibited an excitatory connectivity of 3.9%. In contrast, synaptic connectivity for inhibition was higher in superficial layers though markedly lower than in other cortical areas. Finally, synaptic amplitudes of both excitatory and inhibitory connections showed log-normal distributions suggesting a nonrandom functional connectivity. In summary, our study provides new insights into the microcircuit organization of the presubiculum by revealing area- and layer-specific connectivity rules and sets new constraints for future models of the parahippocampal navigation system. PMID:28334142

  2. Vestibular evoked myogenic potential findings in multiple sclerosis.

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    Escorihuela García, Vicente; Llópez Carratalá, Ignacio; Orts Alborch, Miguel; Marco Algarra, Jaime

    2013-01-01

    Multiple sclerosis is an inflammatory disease involving the occurrence of demyelinating, chronic neurodegenerative lesions in the central nervous system. We studied vestibular evoked myogenic potentials (VEMPs) in this pathology, to allow us to evaluate the saccule, inferior vestibular nerve and vestibular-spinal pathway non-invasively. There were 23 patients diagnosed with multiple sclerosis who underwent VEMP recordings, comparing our results with a control group consisting of 35 healthy subjects. We registered p13 and n23 wave latencies, interaural amplitude difference and asymmetry ratio between both ears. Subjects also underwent an otoscopy and audiometric examination. The prolongation of p13 and n23 wave latencies was the most notable characteristic, with a mean p13 wave latency of 19.53 milliseconds and a mean latency of 30.06 milliseconds for n23. In contrast, the asymmetry index showed no significant differences with our control group. In case of multiple sclerosis, the prolongation of the p13 and n23 VEMP wave latencies is a feature that has been attributed to slowing of conduction by demyelination of the vestibular-spinal pathway. In this regard, alteration of the response or lack thereof in these potentials has a locator value of injury to the lower brainstem. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  3. Resting Heart Rate and Auditory Evoked Potential

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    Simone Fiuza Regaçone

    2015-01-01

    Full Text Available The objective of this study was to evaluate the association between rest heart rate (HR and the components of the auditory evoked-related potentials (ERPs at rest in women. We investigated 21 healthy female university students between 18 and 24 years old. We performed complete audiological evaluation and measurement of heart rate for 10 minutes at rest (heart rate monitor Polar RS800CX and performed ERPs analysis (discrepancy in frequency and duration. There was a moderate negative correlation of the N1 and P3a with rest HR and a strong positive correlation of the P2 and N2 components with rest HR. Larger components of the ERP are associated with higher rest HR.

  4. Visual evoked potentials in rubber factory workers.

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    Tandon, O P; Kumar, V

    1997-01-01

    Pattern reversal visual evoked potentials (pVEP) were studied in 39 male rubber factory workers in the age range of 18-55 years and 20 control subjects (aged 18-46 years) not exposed to the rubber factory environment. Results revealed that 20 (51%) rubber factory workers had abnormal latencies of wave P1 (dominant component of pVEP) as per accepted criteria of 99% tolerance limit set for the control group (i.e. any value above mean +3 SD of control was considered abnormal). The section-wise per cent distribution of abnormalities was vulcanization (83%), tubing (75%), calendering (60%), loading (38%) and mixing (14%). This study provides electrophysiological evidence that rubber factory environments affect the conduction processes in optical pathways from their origin in the retina to striate cortex. However, this study has its limitations in not identifying the specific chemical(s) causing these changes in VEP.

  5. Bayesian analysis of MEG visual evoked responses

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    Schmidt, D.M.; George, J.S.; Wood, C.C.

    1999-04-01

    The authors developed a method for analyzing neural electromagnetic data that allows probabilistic inferences to be drawn about regions of activation. The method involves the generation of a large number of possible solutions which both fir the data and prior expectations about the nature of probable solutions made explicit by a Bayesian formalism. In addition, they have introduced a model for the current distributions that produce MEG and (EEG) data that allows extended regions of activity, and can easily incorporate prior information such as anatomical constraints from MRI. To evaluate the feasibility and utility of the Bayesian approach with actual data, they analyzed MEG data from a visual evoked response experiment. They compared Bayesian analyses of MEG responses to visual stimuli in the left and right visual fields, in order to examine the sensitivity of the method to detect known features of human visual cortex organization. They also examined the changing pattern of cortical activation as a function of time.

  6. Music evokes vicarious emotions in listeners

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    Kawakami, Ai; Furukawa, Kiyoshi; Okanoya, Kazuo

    2014-01-01

    Why do we listen to sad music? We seek to answer this question using a psychological approach. It is possible to distinguish perceived emotions from those that are experienced. Therefore, we hypothesized that, although sad music is perceived as sad, listeners actually feel (experience) pleasant emotions concurrent with sadness. This hypothesis was supported, which led us to question whether sadness in the context of art is truly an unpleasant emotion. While experiencing sadness may be unpleasant, it may also be somewhat pleasant when experienced in the context of art, for example, when listening to sad music. We consider musically evoked emotion vicarious, as we are not threatened when we experience it, in the way that we can be during the course of experiencing emotion in daily life. When we listen to sad music, we experience vicarious sadness. In this review, we propose two sides to sadness by suggesting vicarious emotion. PMID:24910621

  7. RECORDING OF VESTIBULAR EVOKED MYOGENIC POTENTIALS

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    A. A. Sazgar

    2006-05-01

    Full Text Available It has been shown recently that loud clicks evoke myogenic potentials in the tonically contracting sternocleidomastoid muscles. Studies have suggested that these potentials are of vestibular origin, especially of the saccule and inferior vestibular nerve. A pilot study was undertaken in our hospital to record vestibular evoked myogenic potentials (VEMP for the first time in Iran. Eighteen healthy volunteers (32 ears without history of otologic or vestibular disorders were subjected to the VEMP test. Twenty-one patients (26 ears with unilateral (6 patients and bilateral (5 patients high frequency sensorineural hearing loss with unknown etiology, acoustic neuroma (1 patient, Meniere’s disease (4 patients and unilateral low frequency sensorineural hearing loss without vestibular complaint (5 patients were also enrolled in this study. VEMP response to clicks was obtained from 84.4% of ears of healthy subjects. These subjects demonstrated short latency waves to click stimuli during tonic neck flexor activation. Mean latencies of first positive (p13 and first negative (n23 potentials in healthy subjects were 12.45 ± 1.9 ms and 20.8 ± 3.5 ms, respectively. Median latencies of these two potentials were 12.1 and 19.3 ms, respectively. We could record VEMP in 5 patients with unilateral and all patients with high and low frequency sensorineural hearing loss without vestibular complaint. In the patient with acoustic neuroma VEMP was absent on the affected side. This technique may offer a new method to evaluate otolith and sacculocollic pathways in human.

  8. Dexmedetomidine promotes the recovery of the field excitatory postsynaptic potentials (fEPSPs) in rat hippocampal slices exposed to oxygen-glucose deprivation.

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    Kim, Sung-Eun; Ko, Il-Gyu; Kim, Chang-Ju; Chung, Jun-Young; Yi, Jae-Woo; Choi, Jeong-Hyun; Jang, Myung-Soo; Han, Jin-Hee

    2016-09-19

    Dexmedetomidine (DEX), a selective α2 adrenergic agonist, is an anesthetic and sedative agent, and is reported to exert neuroprotective effects after hypoxic ischemia. However, there are few studies on the electrophysiological effect of DEX in hippocampal slices under ischemic conditions. The effects of DEX on field potential in hippocampal slices exposed to oxygen-glucose deprivation (OGD) were evaluated. Hippocampal slices were prepared from rats, and the evoked field excitatory postsynaptic potentials (fEPSPs) were recorded using the MED 64 system. Hypoxic-ischemia was induced by perfusion with glucose-free artificial cerebrospinal fluid (aCSF) bubbled with 95% N2 and 5% CO2, and hippocampal slices were perfused with DEX-added aCSF before, during, and after OGD induction. In the normal hippocampal slices, perfusion with 1 and 10μM DEX did not significantly decrease the normalized fEPSP amplitude, but 100μM DEX significantly reduced the fEPSP amplitude compared with its baseline control. The induction of OGD remarkably decreased the fEPSP amplitude, whereas the pre-, co-, and post-treatment of 10μM DEX gradually promoted recovery after washing out, and consequently the amplitude of fEPSP in DEX pre-, co-, and post-treated OGD slices were significantly higher than that in the untreated OGD slices at 10min and 60min after washing out. In particular, co-treatment with DEX conspicuously promoted the recovery of the fEPSP amplitude at the beginning of washing out. These results suggest the possibility of DEX as a therapeutic agent to prevent hypoxic-ischemic brain damage and promote functional recovery after ischemia. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

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    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.

  10. NR2 subunits and NMDA receptors on lamina II inhibitory and excitatory interneurons of the mouse dorsal horn

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    MacDermott Amy B

    2010-05-01

    Full Text Available Abstract Background NMDA receptors expressed by spinal cord neurons in the superficial dorsal horn are involved in the development of chronic pain associated with inflammation and nerve injury. The superficial dorsal horn has a complex and still poorly understood circuitry that is mainly populated by inhibitory and excitatory interneurons. Little is known about how NMDA receptor subunit composition, and therefore pharmacology and voltage dependence, varies with neuronal cell type. NMDA receptors are typically composed of two NR1 subunits and two of four NR2 subunits, NR2A-2D. We took advantage of the differences in Mg2+ sensitivity of the NMDA receptor subtypes together with subtype preferring antagonists to identify the NR2 subunit composition of NMDA receptors expressed on lamina II inhibitory and excitatory interneurons. To distinguish between excitatory and inhibitory interneurons, we used transgenic mice expressing enhanced green fluorescent protein driven by the GAD67 promoter. Results Analysis of conductance ratio and selective antagonists showed that lamina II GABAergic interneurons express both the NR2A/B containing Mg2+ sensitive receptors and the NR2C/D containing NMDA receptors with less Mg2+ sensitivity. In contrast, excitatory lamina II interneurons express primarily NR2A/B containing receptors. Despite this clear difference in NMDA receptor subunit expression in the two neuronal populations, focally stimulated synaptic input is mediated exclusively by NR2A and 2B containing receptors in both neuronal populations. Conclusions Stronger expression of NMDA receptors with NR2C/D subunits by inhibitory interneurons compared to excitatory interneurons may provide a mechanism to selectively increase activity of inhibitory neurons during intense excitatory drive that can provide inhibitory feedback.

  11. Excitatory Hindbrain-Forebrain Communication Is Required for Cisplatin-Induced Anorexia and Weight Loss.

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    Alhadeff, Amber L; Holland, Ruby A; Zheng, Huiyuan; Rinaman, Linda; Grill, Harvey J; De Jonghe, Bart C

    2017-01-11

    Cisplatin chemotherapy is commonly used to treat cancer despite severe energy balance side effects. In rats, cisplatin activates nucleus tractus solitarius (NTS) projections to the lateral parabrachial nucleus (lPBN) and calcitonin-gene related peptide (CGRP) projections from the lPBN to the central nucleus of the amygdala (CeA). We demonstrated previously that CeA glutamate receptor signaling mediates cisplatin-induced anorexia and body weight loss. Here, we used neuroanatomical tracing, immunofluorescence, and confocal imaging to demonstrate that virtually all NTS→lPBN and lPBN→CeA CGRP projections coexpress vesicular glutamate transporter 2 (VGLUT2), providing evidence that excitatory projections mediate cisplatin-induced energy balance dysregulation. To test whether lPBN→CeA projection neurons are required for cisplatin-induced anorexia and weight loss, we inhibited these neurons chemogenetically using a retrograde Cre-recombinase-expressing canine adenovirus-2 in combination with Cre-dependent inhibitory Designer Receptors Exclusive Activated by Designer Drugs (DREADDs) before cisplatin treatment. Inhibition of lPBN→CeA neurons attenuated cisplatin-induced anorexia and body weight loss significantly. Using a similar approach, we additionally demonstrated that inhibition of NTS→lPBN neurons attenuated cisplatin-induced anorexia and body weight loss significantly. Together, our data support the view that excitatory hindbrain-forebrain projections are necessary for cisplatin's untoward effects on energy intake, elucidating a key neuroanatomical circuit driving pathological anorexia and weight loss that accompanies chemotherapy treatment. Chemotherapy treatments are commonly used to treat cancers despite accompanying anorexia and weight loss that may limit treatment adherence and reduce patient quality of life. Strikingly, we lack a neural understanding of, and effective treatments for, chemotherapy-induced anorexia and weight loss. The current data

  12. Action of thymol on spontaneous excitatory transmission in adult rat spinal substantia gelatinosa neurons.

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    Xu, Zhi-Hao; Wang, Chong; Fujita, Tsugumi; Jiang, Chang-Yu; Kumamoto, Eiichi

    2015-10-08

    Thymol, which is contained in thyme essential oil, has various actions including antinociception and nerve conduction inhibition. Although thymol activates transient receptor potential (TRP) channels expressed in heterologous cells, it remains to be examined whether this is so in native neurons. It has not yet been examined how thymol affects synaptic transmission. In order to know how thymol modulates excitatory transmission with a focus on TRP activation, we investigated its effect on glutamatergic spontaneous excitatory transmission in lamina II (substantia gelatinosa; SG) neurons with which nerve terminals expressing TRP channels make synaptic contacts. The experiment was performed by using the blind whole-cell patch-clamp technique in adult rat spinal cord slices. Superfusing thymol (1 mM) for 3 min reversibly increased the frequency of spontaneous excitatory postsynaptic current (sEPSC) with a minimal increase in its amplitude in all neurons examined. Seventy-seven% of the neurons produced an outward current at a holding potential of -70 mV. The sEPSC frequency increase and outward current produced by thymol were concentration-dependent with almost the same half-maximal effective concentration (EC50) values of 0.18 and 0.14 mM, respectively. These activities were repeated at a time interval of 30 min, although the sEPSC frequency increase but not outward current recovered with a slow time course. Voltage-gated Na(+)-channel blocker tetrodotoxin did not affect the thymol activities. The sEPSC frequency increase was inhibited by TRPA1 antagonist HC-030031 but not TRPV1 and TRPM8 antagonist (capsazepine and BCTC, respectively), while these antagonists had no effect on the outward current. This was so, albeit the two thymol activities had similar EC50 values. It is concluded that thymol increases the spontaneous release of L-glutamate onto SG neurons by activating TRPA1 channels while producing an outward current without TRP activation. Considering that the SG

  13. Electrocochleography potentials evoked by condensation and rarefaction clicks independently derived by a new numerical filtering approach.

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    Sparacino, G; Milani, S; Magnavita, V; Arslan, E

    2000-01-01

    The cochlear microphonic potential (CM) and the compound action potential (CAP) cannot be measured separately but only in combination. In the literature their individual estimates are conventionally recovered by the so-called CM cancellation technique. This method averages the potential obtained in response to rarefaction and condensation clicks under the assumption that changing the polarity of the clicks only affects the CM sign and does not alter the CAP in any way. However, both theory and evidence suggest that these hypotheses can be critical. In addition, recent contributions in the electrocochleography (ECochG) literature suggested that assessing the influence of stimulus polarity on the evoked CAP may constitute an indicator of clinical usefulness which the CM cancellation method cannot supply. In this work we propose a new algorithm to estimate the cochlear potentials evoked from positive clicks, CAP+ and CM+, and those evoked from negative clicks, CAP- and CM-, by processing the same kind and amount of data employed in the CM cancellation method. The application to real data taken from 3 subjects exhibiting quantitatively and qualitatively different ECochG responses at various levels of stimulation intensity is presented. In addition, simulated problems where the true CAP and CM are known are studied to permit a fair assessment of the proposed technique. Results suggest that the new algorithm is potentially able to point out small differences between CAP+ and CAP-. This encourages its further employment on a larger scale. Copyright 2000 S. Karger AG, Basel

  14. Hyperosmolarity evokes histamine release from ileum mucosa by stimulating a cholinergic pathway.

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    Wang, Banqin; An, Ning; Shaikh, Abdul Sami; Wang, Haoyi; Xiao, Ling; Liu, Hongwei; Li, Jingxin; Zhao, Dongbo

    2017-11-18

    Changes in extracellular osmolarity lead to alteration in cellular volume. In the study, we examined the effects of hyperosmolarity on short-circuit currents (Isc) in the rat ileum using the Ussing chamber technique. Mucosal exposure to 20 mM glucose evoked a decrease of ISC in the rat ileum, which was antagonized by the stretch-activated channel blocker GdCl3, TTX and atropine, respectively. In contrast, it was not blocked by phlorizin, a Na+-glucose cotransporter SGLT1 inhibitor. Furthermore, the unabsorbed substances, such as sucrose, lactulose or urea, also induced a decrease of ISC in rat ileum. ELISA results revealed that 20 mM glucose stimulated the release of histamine from rat ileum mucosa, which was attenuated by TTX. In addition, the glucose-induced ISC was depressed by pyrilamine, a histamine H1 receptor blocker (H1 antagonist) whereas it was not affected by ranitidine (H2 antagonist), clobenpropit (H3 antagonists) or JNJ7777120 (H4 antagonist), respectively. The ion substitution experiments suggest that the changes of Na+ and HCO3- ion flux underlie the glucose-induced ISC. In conclusion, osmotic stimulus decreased the basal ISC of rat ileum by evoking histamine release from ileum mucosa. The changes of Na+ and HCO3- ion transport are involved in the glucose-evoked decrease of basal ISC. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Evaluation of Visual Evoked Potentials in Patient with Angelmans Syndrome - Case Report

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    Tatjana Knezevic

    2013-06-01

    Full Text Available Background: Angelman syndrome (AS is a genetic disorder with varying degrees of neurological impairment. It is often associated with ocular involvement. Case Report: We present a child diagnosed with AS who had a deletion on the short arm of chromosome 15. The child seemed to be happy, with developmental delay, speech problem, and altering strabismus. To assess the potential presence and degree of damage in the visual pathway, we recorded monocular flash visual evoked potentials (VEPs. Our results revealed the presence of severe central afferent dysfunction in both optical pathways. Conclusion: VEPs can be used in patients with AS and visual disturbances to assess the integrity of the visual system.

  16. 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

  17. Localized infusions of the partial alpha 7 nicotinic receptor agonist SSR180711 evoke rapid and transient increases in prefrontal glutamate release

    DEFF Research Database (Denmark)

    Bortz, D M; Mikkelsen, J D; Bruno, J P

    2013-01-01

    that inhibited (threo-beta-benzyl-oxy-aspartate (TβOA), 100.0μM) or facilitated (ceftriaxalone, 200mg/kg, i.p.) excitatory amino acid transporters. TβOA slowed both the clearance (s) and rate of clearance (μM/s) by 10-fold, particularly at the mid-late stages of the return to baseline. Ceftriaxone reduced......The ability of local infusions of the alpha 7 nicotinic acetycholine receptor (α7 nAChR) partial agonist SSR180711 to evoke glutamate release in prefrontal cortex was determined in awake rats using a microelectrode array. Infusions of SSR180711 produced dose-dependent increases in glutamate levels...

  18. Glutathione in Cellular Redox Homeostasis: Association with the Excitatory Amino Acid Carrier 1 (EAAC1

    Directory of Open Access Journals (Sweden)

    Koji Aoyama

    2015-05-01

    Full Text Available Reactive oxygen species (ROS are by-products of the cellular metabolism of oxygen consumption, produced mainly in the mitochondria. ROS are known to be highly reactive ions or free radicals containing oxygen that impair redox homeostasis and cellular functions, leading to cell death. Under physiological conditions, a variety of antioxidant systems scavenge ROS to maintain the intracellular redox homeostasis and normal cellular functions. This review focuses on the antioxidant system’s roles in maintaining redox homeostasis. Especially, glutathione (GSH is the most important thiol-containing molecule, as it functions as a redox buffer, antioxidant, and enzyme cofactor against oxidative stress. In the brain, dysfunction of GSH synthesis leading to GSH depletion exacerbates oxidative stress, which is linked to a pathogenesis of aging-related neurodegenerative diseases. Excitatory amino acid carrier 1 (EAAC1 plays a pivotal role in neuronal GSH synthesis. The regulatory mechanism of EAAC1 is also discussed.

  19. Plasticity of Hippocampal Excitatory-Inhibitory Balance: Missing the Synaptic Control in the Epileptic Brain.

    Science.gov (United States)

    Bonansco, Christian; Fuenzalida, Marco

    2016-01-01

    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.

  20. Ionotropic excitatory amino acid receptor ligands. Synthesis and pharmacology of a new amino acid AMPA antagonist

    DEFF Research Database (Denmark)

    Madsen, U; Sløk, F A; Stensbøl, T B

    2000-01-01

    We have previously described the potent and selective (RS)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) receptor agonist, (RS)-2-amino-3-(3-carboxy-5-methyl-4-isoxazolyl)propionic acid (ACPA), and the AMPA receptor antagonist (RS)-2-amino-3-[3-(carboxymethoxy)-5-methyl-4......-isoxazolyl]propionic acid (AMOA). Using these AMPA receptor ligands as leads, a series of compounds have been developed as tools for further elucidation of the structural requirements for activation and blockade of AMPA receptors. The synthesized compounds have been tested for activity at ionotropic...... excitatory amino acid (EAA) receptors using receptor binding and electrophysiological techniques, and for activity at metabotropic EAA receptors using second messenger assays. Compounds 1 and 4 were essentially inactive. (RS)-2-Amino-3-[3-(2-carboxyethyl)-5-methyl-4-isoxazolyl]propionic acid (ACMP, 2...

  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. Chaos and Correlated Avalanches in Excitatory Neural Networks with Synaptic Plasticity

    Science.gov (United States)

    Pittorino, Fabrizio; Ibáñez-Berganza, Miguel; di Volo, Matteo; Vezzani, Alessandro; Burioni, Raffaella

    2017-03-01

    A collective chaotic phase with power law scaling of activity events is observed in a disordered mean field network of purely excitatory leaky integrate-and-fire neurons with short-term synaptic plasticity. The dynamical phase diagram exhibits two transitions from quasisynchronous and asynchronous regimes to the nontrivial, collective, bursty regime with avalanches. In the homogeneous case without disorder, the system synchronizes and the bursty behavior is reflected into a period doubling transition to chaos for a two dimensional discrete map. Numerical simulations show that the bursty chaotic phase with avalanches exhibits a spontaneous emergence of persistent time correlations and enhanced Kolmogorov complexity. Our analysis reveals a mechanism for the generation of irregular avalanches that emerges from the combination of disorder and deterministic underlying chaotic dynamics.

  3. Sex differences in pudendal somatosensory evoked potentials.

    Science.gov (United States)

    Pelliccioni, G; Piloni, V; Sabbatini, D; Fioravanti, P; Scarpino, O

    2014-06-01

    Somatosensory evoked potentials (SEPs) of the pudendal nerve are a well-established diagnostic tool for the evaluation of pelvic floor disorders. However, the possible influence of sex differences on response latencies has not been established yet. The aim of this study was to standardize the procedures and to evaluate possible effects of gender differences on anal and penile/clitoral SEPs. The anal and dorsal penile/clitoral SEPs were recorded in 84 healthy subjects (40 males and 44 females; mean age 47.9 ± 16.6 years, range 16-81 years; mean height 168.3 ± 20.3 cm, range 155-187 cm). Pudendal SEPs were evoked with a bipolar surface electrode stimulating the clitoris or the base of the penis and the anal orifice and recorded using scalp electrodes. The latency of the first positive component (P1) was measured. The effect and possible interaction of (a) stimulation site and (b) gender on the two variables was explored by multivariate analysis of variance (MANOVA). The examination was well tolerated and a reproducible waveform of sufficient quality was obtained in all the subjects examined. In the female subjects, a mean cortical P1 latency of 37.0 ± 2.6 and 36.4 ± 3.2 ms for anal and clitoral stimulation, respectively, was found. In the male subjects, the cortical latencies were 38.0 ± 3.5 ms for the anal stimulation and 40.2 ± 3.7 ms for the penile stimulation. At MANOVA, a statistically significant main effect of stimulation site and gender as well as a significant interaction between the two variables was found. Anal and dorsal penile/clitoral SEPs represent a well-tolerated and reproducible method to assess the functional integrity of the sensory pathways in male and female subjects. Obtaining sex-specific reference data, by individual electrophysiological testing, is highly recommended because of significant latency differences between males and females, at least as far as penile/clitoral responses are concerned.

  4. N-cofilin can compensate for the loss of ADF in excitatory synapses.

    Science.gov (United States)

    Görlich, Andreas; Wolf, Michael; Zimmermann, Anika-Maria; Gurniak, Christine B; Al Banchaabouchi, Mumna; Sassoè-Pognetto, Marco; Witke, Walter; Friauf, Eckhard; Rust, Marco B

    2011-01-01

    Actin plays important roles in a number of synaptic processes, including synaptic vesicle organization and exocytosis, mobility of postsynaptic receptors, and synaptic plasticity. However, little is known about the mechanisms that control actin at synapses. Actin dynamics crucially depend on LIM kinase 1 (LIMK1) that controls the activity of the actin depolymerizing proteins of the ADF/cofilin family. While analyses of mouse mutants revealed the importance of LIMK1 for both pre- and postsynaptic mechanisms, the ADF/cofilin family member n-cofilin appears to be relevant merely for postsynaptic plasticity, and not for presynaptic physiology. By means of immunogold electron microscopy and immunocytochemistry, we here demonstrate the presence of ADF (actin depolymerizing factor), a close homolog of n-cofilin, in excitatory synapses, where it is particularly enriched in presynaptic terminals. Surprisingly, genetic ablation of ADF in mice had no adverse effects on synapse structure or density as assessed by electron microscopy and by the morphological analysis of Golgi-stained hippocampal pyramidal cells. Moreover, a series of electrophysiological recordings in acute hippocampal slices revealed that presynaptic recruitment and exocytosis of synaptic vesicles as well as postsynaptic plasticity were unchanged in ADF mutant mice. The lack of synaptic defects may be explained by the elevated n-cofilin levels observed in synaptic structures of ADF mutants. Indeed, synaptic actin regulation was impaired in compound mutants lacking both ADF and n-cofilin, but not in ADF single mutants. From our results we conclude that n-cofilin can compensate for the loss of ADF in excitatory synapses. Further, our data suggest that ADF and n-cofilin cooperate in controlling synaptic actin content.

  5. N-cofilin can compensate for the loss of ADF in excitatory synapses.

    Directory of Open Access Journals (Sweden)

    Andreas Görlich

    Full Text Available Actin plays important roles in a number of synaptic processes, including synaptic vesicle organization and exocytosis, mobility of postsynaptic receptors, and synaptic plasticity. However, little is known about the mechanisms that control actin at synapses. Actin dynamics crucially depend on LIM kinase 1 (LIMK1 that controls the activity of the actin depolymerizing proteins of the ADF/cofilin family. While analyses of mouse mutants revealed the importance of LIMK1 for both pre- and postsynaptic mechanisms, the ADF/cofilin family member n-cofilin appears to be relevant merely for postsynaptic plasticity, and not for presynaptic physiology. By means of immunogold electron microscopy and immunocytochemistry, we here demonstrate the presence of ADF (actin depolymerizing factor, a close homolog of n-cofilin, in excitatory synapses, where it is particularly enriched in presynaptic terminals. Surprisingly, genetic ablation of ADF in mice had no adverse effects on synapse structure or density as assessed by electron microscopy and by the morphological analysis of Golgi-stained hippocampal pyramidal cells. Moreover, a series of electrophysiological recordings in acute hippocampal slices revealed that presynaptic recruitment and exocytosis of synaptic vesicles as well as postsynaptic plasticity were unchanged in ADF mutant mice. The lack of synaptic defects may be explained by the elevated n-cofilin levels observed in synaptic structures of ADF mutants. Indeed, synaptic actin regulation was impaired in compound mutants lacking both ADF and n-cofilin, but not in ADF single mutants. From our results we conclude that n-cofilin can compensate for the loss of ADF in excitatory synapses. Further, our data suggest that ADF and n-cofilin cooperate in controlling synaptic actin content.

  6. The Drosophila Postsynaptic DEG/ENaC Channel ppk29 Contributes to Excitatory Neurotransmission.

    Science.gov (United States)

    Hill, Alexis; Zheng, Xingguo; Li, Xiling; McKinney, Ross; Dickman, Dion; Ben-Shahar, Yehuda

    2017-03-22

    The protein family of degenerin/epithelial sodium channels (DEG/ENaCs) is composed of diverse animal-specific, non-voltage-gated ion channels that play important roles in regulating cationic gradients across epithelial barriers. Some family members are also enriched in neural tissues in both vertebrates and invertebrates. However, the specific neurophysiological functions of most DEG/ENaC-encoding genes remain poorly understood. The fruit fly Drosophila melanogaster is an excellent model for deciphering the functions of DEG/ENaC genes because its genome encodes an exceptionally large number of DEG/ENaC subunits termed pickpocket (ppk) 1-31 Here we demonstrate that ppk29 contributes specifically to the postsynaptic modulation of excitatory synaptic transmission at the larval neuromuscular junction. Electrophysiological data indicate that the function of ppk29 in muscle is necessary for normal postsynaptic responsivity to neurotransmitter release and for normal coordinated larval movement. The ppk29 mutation does not affect gross synaptic morphology and ultrastructure, which indicates that the observed phenotypes are likely due to defects in glutamate receptor function. Together, our data indicate that DEG/ENaC ion channels play a fundamental role in the postsynaptic regulation of excitatory neurotransmission.SIGNIFICANCE STATEMENT Members of the degenerin/epithelial sodium channel (DEG/ENaC) family are broadly expressed in epithelial and neuronal tissues. To date, the neurophysiological functions of most family members remain unknown. Here, by using the power of Drosophila genetics in combination with electrophysiological and behavioral approaches, we demonstrate that the DEG/ENaC-encoding gene pickpocket 29 contributes to baseline neurotransmission, possibly via the modulation of postsynaptic glutamate receptor functionality. Copyright © 2017 the authors 0270-6474/17/373171-10$15.00/0.

  7. Opioid Tolerance and Physical Dependence: Role of Spinal Neuropeptides, Excitatory Amino Acids and Their Messengers

    Directory of Open Access Journals (Sweden)

    Khem Jhamandas

    2000-01-01

    Full Text Available Chronic opioid treatment results in the development of tolerance and physical dependence. The mechanisms underlying opioid tolerance and/or physical dependence are unclear. Recent studies suggest that opioid receptor or nociceptive, neural network-based adaptations contribute to this phenomenon. At the spinal level, the genesis of tolerance and physical dependence is associated with increased excitatory amino acid activity expressed through N-methyl-D-aspartate receptors in the dorsal horn. However, recent evidence also implicates spinal neuropeptide transmitters such as calcitonin gene-related peptide (CGRP and  substance P in the development of opioid tolerance. Long term spinal morphine treatment increases CGRP-like immunostaining in the dorsal horn, and coadministration of morphine with CGRP8-37, a competitive CGRP1 receptor antagonist, prevents this response as well as loss of the analgesic potency. CGRP8-37, like N-methyl-D-aspartate receptor antagonists, has the potential to restore morphine potency in experimental animals who are already tolerant to the opioid agonist. Recent evidence suggests that the effects of excitatory amino acid and neuropeptide receptor activity may be expressed through the generation of messengers such as nitric oxide and prostanoids. Agents that inhibit the synthesis of nitric oxide and prostanoids have the potential to inhibit and reverse spinal opioid tolerance, suggesting that this phenomenon may be expressed through the activity of these mediators. Nociceptive transmission in the dorsal horn of the spinal cord also involves activity of a number of other mediators including morphine modulatory neuropeptides, neuropeptide FF  and neuropeptide SF. The role of these mediators and their relationship with other factors implicated in tolerance remain to be determined.

  8. 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

  9. 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.

  10. Organization of binaural excitatory and inhibitory inputs to the inferior colliculus from the superior olive.

    Science.gov (United States)

    Loftus, William C; Bishop, Deborah C; Saint Marie, Richard L; Oliver, Douglas L

    2004-05-03

    The major excitatory, binaural inputs to the central nucleus of the inferior colliculus (ICC) are from two groups of neurons with different functions-the ipsilateral medial superior olive (MSO) and the contralateral lateral superior olive (LSO). A major inhibitory, binaural input emerges from glycinergic neurons in the ipsilateral LSO. To determine whether these inputs converge on the same postsynaptic targets in the ICC, two different anterograde tracers were injected in tonotopically matched areas of the MSO and the LSO on the opposite side in the same animal. The main findings were that the boutons from MSO axons terminated primarily in the central and caudal parts of the ICC laminae but that contralateral LSO terminals were concentrated more rostrally and on the ventral margins of the MSO inputs. In contrast, the ipsilateral LSO projection converged with the MSO inputs and was denser than the contralateral LSO projection. Consistent with this finding, retrograde transport experiments showed that the very low-frequency areas of the ICC with dense MSO inputs also received inputs from greater numbers of ipsilateral LSO neurons than from contralateral LSO neurons. The results suggest that different binaural pathways through the low-frequency ICC may be formed by the segregation of excitatory inputs to ICC from the MSO and the contralateral LSO. At the same time, the ipsilateral LSO is a major inhibitory influence in the target region of the MSO. These data support the concept that each frequency-band lamina in the ICC may comprise several functional modules with different combinations of inputs. Copyright 2004 Wiley-Liss, Inc.

  11. Dynamics of networks of excitatory and inhibitory neuronsin response to time-dependent inputs

    Directory of Open Access Journals (Sweden)

    Erwan eLedoux

    2011-05-01

    Full Text Available We investigate the dynamics of recurrent networks of excitatory (E and inhibitory(I neurons in the presence of time-dependent inputs. The dynamics is characterizedby the network dynamical transfer function, i.e. how the population firing rate ismodulated by sinusoidal inputs at arbitrary frequencies. Two types of networks arestudied and compared: (i a Wilson-Cowan type firing rate model; and (ii a fullyconnected network of leaky integrate-and-fire neurons, in a strong noise regime. Wefirst characterize the region of stability of the ‘asynchronous state’ (a state in whichpopulation activity is constant in time when external inputs are constant in the spaceof parameters characterizing the connectivity of the network. We then systematicallycharacterize the qualitative behaviors of the dynamical transfer function, as a functionof the connectivity. We find that the transfer function can be either low-pass, or witha single or double resonance, depending on the connection strengths and synaptic timeconstants. Resonances appear when the system is close to Hopf bifurcations, that canbe induced by two separate mechanisms: the I-I connectivity and the E-I connectivity.Double resonances can appear when excitatory delays are larger than inhibitory delays,due to the fact that two distinct instabilities exist with a finite gap between thecorresponding frequencies. In networks of LIF neurons, changes in external inputs andexternal noise are shown to be able to change qualitatively the network transfer function.Firing rate models are shown to exhibit the same diversity of transfer functions asthe LIF network, provided delays are present. They can also exhibit input-dependentchanges of the transfer function, provided a suitable static nonlinearity is incorporated.

  12. Therapeutic testosterone administration preserves excitatory synaptic transmission in the hippocampus during autoimmune demyelinating disease.

    Science.gov (United States)

    Ziehn, Marina O; Avedisian, Andrea A; Dervin, Shannon M; Umeda, Elizabeth A; O'Dell, Thomas J; Voskuhl, Rhonda R

    2012-09-05

    Over 50% of multiple sclerosis (MS) patients experience cognitive deficits, and hippocampal-dependent memory impairment has been reported in >30% of these patients. While postmortem pathology studies and in vivo magnetic resonance imaging demonstrate that the hippocampus is targeted in MS, the neuropathology underlying hippocampal dysfunction remains unknown. Furthermore, there are no treatments available to date to effectively prevent neurodegeneration and associated cognitive dysfunction in MS. We have recently demonstrated that the hippocampus is also targeted in experimental autoimmune encephalomyelitis (EAE), the most widely used animal model of MS. The objective of this study was to assess whether a candidate treatment (testosterone) could prevent hippocampal synaptic dysfunction and underlying pathology when administered in either a preventative or a therapeutic (postdisease induction) manner. Electrophysiological studies revealed impairments in basal excitatory synaptic transmission that involved both AMPA receptor-mediated changes in synaptic currents, and faster decay rates of NMDA receptor-mediated currents in mice with EAE. Neuropathology revealed atrophy of the pyramidal and dendritic layers of hippocampal CA1, decreased presynaptic (Synapsin-1) and postsynaptic (postsynaptic density 95; PSD-95) staining, diffuse demyelination, and microglial activation. Testosterone treatment administered either before or after disease induction restores excitatory synaptic transmission as well as presynaptic and postsynaptic protein levels within the hippocampus. Furthermore, cross-modality correlations demonstrate that fluctuations in EPSPs are significantly correlated to changes in postsynaptic protein levels and suggest that PSD-95 is a neuropathological substrate to impaired synaptic transmission in the hippocampus during EAE. This is the first report demonstrating that testosterone is a viable therapeutic treatment option that can restore both hippocampal

  13. Training Excitatory-Inhibitory Recurrent Neural Networks for Cognitive Tasks: A Simple and Flexible Framework.

    Directory of Open Access Journals (Sweden)

    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

  14. Maternal Immune Activation Delays Excitatory-to-Inhibitory Gamma-Aminobutyric Acid Switch in Offspring.

    Science.gov (United States)

    Corradini, Irene; Focchi, Elisa; Rasile, Marco; Morini, Raffaella; Desiato, Genni; Tomasoni, Romana; Lizier, Michela; Ghirardini, Elsa; Fesce, Riccardo; Morone, Diego; Barajon, Isabella; Antonucci, Flavia; Pozzi, Davide; Matteoli, Michela

    2017-11-14

    The association between maternal infection and neurodevelopmental defects in progeny is well established, although the biological mechanisms and the pathogenic trajectories involved have not been defined. Pregnant dams were injected intraperitoneally at gestational day 9 with polyinosinic:polycytidylic acid. Neuronal development was assessed by means of electrophysiological, optical, and biochemical analyses. Prenatal exposure to polyinosinic:polycytidylic acid causes an imbalanced expression of the Na+-K+-2Cl- cotransporter 1 and the K+-Cl- cotransporter 2 (KCC2). This results in delayed gamma-aminobutyric acid switch and higher susceptibility to seizures, which endures up to adulthood. Chromatin immunoprecipitation experiments reveal increased binding of the repressor factor RE1-silencing transcription (also known as neuron-restrictive silencer factor) to position 509 of the KCC2 promoter that leads to downregulation of KCC2 transcription in prenatally exposed offspring. Interleukin-1 receptor type I knockout mice, which display braked immune response and no brain cytokine elevation upon maternal immune activation, do not display KCC2/Na+-K+-2Cl- cotransporter 1 imbalance when implanted in a wild-type dam and prenatally exposed. Notably, pretreatment of pregnant dams with magnesium sulfate is sufficient to prevent the early inflammatory state and the delay in excitatory-to-inhibitory switch associated to maternal immune activation. We provide evidence that maternal immune activation hits a key neurodevelopmental process, the excitatory-to-inhibitory gamma-aminobutyric acid switch; defects in this switch have been unequivocally linked to diseases such as autism spectrum disorder or epilepsy. These data open the avenue for a safe pharmacological treatment that may prevent the neurodevelopmental defects caused by prenatal immune activation in a specific pregnancy time window. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights

  15. 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.

  16. Excitatory effects induced by carbachol on bursting neurons of the rat subiculum.

    Science.gov (United States)

    Kawasaki, H; Avoli, M

    1996-11-15

    Conventional intracellular recordings were made from neurons of the rat subiculum in an in vitro slice preparation. Intracellular pulses of depolarizing current (duration, 10-120 ms) delivered at a resting membrane potential of -62.2 +/- 7.7 mV (mean +/- SD, n = 14) induced bursts of 3-5 fast, action potentials riding on a slow depolarization. The burst was terminated by an afterhyperpolarization (burst AHP) that lasted 117 +/- 26 ms and reached peak amplitude of 5.1 +/- 1.8 mV (n = 8). Bath application of the cholinergic agonist carbachol (CCh; 30-100 microM; n = 20) in the presence of ionotropic excitatory amino acid receptor antagonists induced a steady depolarization (4.6 +/- 2.7 mV) of the membrane potential, and a small increase in input resistance. Action potential bursts continued to occur in response to intracellular depolarizing pulses during CCh application. However, this cholinergic agonist reduced and eventually blocked the burst AHP, which was replaced by action potentials firing. In the presence of CCh (> 70 microM; n = 9) the burst response, was followed by a depolarizing plateau potential (PP) that outlasted the intracellular depolarizing pulse by 731 +/- 386 ms (range 160-1900 ms), and could trigger repetitive action potential firing at 35-116 Hz. The effects induced by CCh were reversed by bath application of the muscarinic antagonist atropine (0.5-1 microM; n = 4). Our findings demonstrate that CCh exerts in the rat subiculum an excitatory action that is dependent upon muscarinic receptor stimulation. This cholinergic mechanism may play a physiological role in the subicular processing of signals arising from the hippocampus proper, and may also contribute to the generation of sustained epileptiform discharges induced in the limbic system by cholinergic agents.

  17. Decreased serotonin level during pregnancy alters morphological and functional characteristics of tonic nociceptive system in juvenile offspring of the rat

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    Mikhailenko Victor A

    2003-11-01

    Full Text Available Abstract Serotonin (5-HT contributes to the prenatal development of the central nervous system, acting as a morphogen in the young embryo and later as a neurotransmitter. This biologically active agent influences both morphological and biochemical differentiation of raphe neurons, which give rise to the descending serotonergic paths that regulate the processing of acutely evoked nociceptive inputs. The involvement of 5-HT in the prenatal development of tonic nociceptive system has not been studied. In the present study we evaluated the effects of a single injection (400 mg/kg, 2 ml, i.p. of the 5-HT synthesis inhibitor, para-chlorophenylalanine (pCPA, given to pregnant rats during the critical period fetal serotonin development. The functional integrity of the tonic nociceptive response was investigated in 25 day old rats using the classic formalin test. Morphological analysis of brain structures involved in formalin-induced pain and 5-HT levels in the heads of 12-day embryos were also evaluated. Embryonic levels of 5-HT were significantly lowered by the treatment. The juvenile rats from pCPA-treated females showed altered brain morphology and cell differentiation in the developing cortex, hippocampus, raphe nuclei, and substantia nigra. In the formalin test, there were significant decreases in the intensity and duration of the second phase of the formalin-induced response, characterizing persistent, tonic pain. The extent of impairments in the brain structures correlated positively with the level of decrease in the behavioral responses. The data demonstrate the involvement of 5-HT in the prenatal development of the tonic nociceptive system. The decreased tonic component of the behavioral response can be explained by lower activity of the descending excitatory serotonergic system originating in the raphe nuclei, resulting in decreased tonic pain processing organized at the level of the dorsal horn of the spinal cord.

  18. Visually evoked spiking evolves while spontaneous ongoing dynamics persist

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    Raoul eHuys

    2016-01-01

    Full Text Available 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.

  19. Transient evoked otoacoustic emissions in rock musicians.

    Science.gov (United States)

    Høydal, Erik Harry; Lein Størmer, Carl Christian; Laukli, Einar; Stenklev, Niels Christian

    2017-09-01

    Our focus in this study was the assessment of transient evoked otoacoustic emissions (TEOAEs) in a large group of rock musicians. A further objective was to analyse tinnitus among rock musicians as related to TEOAEs. The study was a cross-sectional survey of rock musicians selected at random. A control group was included at random for comparison. We recruited 111 musicians and a control group of 40 non-musicians. Testing was conducted by using clinical examination, pure tone audiometry, TEOAEs and a questionnaire. TEOAE SNR in the half-octave frequency band centred on 4 kHz was significantly lower bilaterally in musicians than controls. This effect was strongly predicted by age and pure-tone hearing threshold levels in the 3-6 kHz range. Bilateral hearing thresholds were significantly higher at 6 kHz in musicians. Twenty percent of the musicians had permanent tinnitus. There was no association between the TEOAE parameters and permanent tinnitus. Our results suggest an incipient hearing loss at 6 kHz in rock musicians. Loss of TEOAE SNR in the 4 kHz half-octave frequency band was observed, but it was related to higher mean 3-6 kHz hearing thresholds and age. A large proportion of rock musicians have permanent tinnitus.

  20. Visual evoked potential study in slow learners.

    Science.gov (United States)

    Khaliq, Farah; Anjana, Yumnam; Vaney, Neelam

    2009-01-01

    Slow learners are individuals with low achievement and comparably low IQ scores. It may be a symptom reflecting a larger underlying problem in them. Sensory neural processing of visual information can be one of the contributory factors for their underachievement. The present study was undertaken to examine the integrity and function of visual pathway by means of Visual Evoked Potential (VEP). Pattern reversal VEP was performed on seventeen slow learners. Fifteen age and sex matched children with good school performance and normal IQ were taken as controls. There was significant prolongation of N75 component of VEP in slow learners. The latencies of P100 and N145 were also increased but could not reach the level of significance. Our findings are suggestive of the presence of a weaker VEP response in slow learners indicative of a deficit early in the visual processing. There is some abnormality in the geniculate afferents to V1 which is consistent with a defect in the magnocellular pathway at the level of Visual Area 1 or earlier.

  1. 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...

  2. Calcium Channel α2δ1 Proteins Mediate Trigeminal Neuropathic Pain States Associated with Aberrant Excitatory Synaptogenesis*

    Science.gov (United States)

    Li, Kang-Wu; Yu, Yanhui Peter; Zhou, Chunyi; Kim, Doo-Sik; Lin, Bin; Sharp, Kelli; Steward, Oswald; Luo, Z. David

    2014-01-01

    To investigate a potential mechanism underlying trigeminal nerve injury-induced orofacial hypersensitivity, we used a rat model of chronic constriction injury to the infraorbital nerve (CCI-ION) to study whether CCI-ION caused calcium channel α2δ1 (Cavα2δ1) protein dysregulation in trigeminal ganglia and associated spinal subnucleus caudalis and C1/C2 cervical dorsal spinal cord (Vc/C2). Furthermore, we studied whether this neuroplasticity contributed to spinal neuron sensitization and neuropathic pain states. CCI-ION caused orofacial hypersensitivity that correlated with Cavα2δ1 up-regulation in trigeminal ganglion neurons and Vc/C2. Blocking Cavα2δ1 with gabapentin, a ligand for the Cavα2δ1 proteins, or Cavα2δ1 antisense oligodeoxynucleotides led to a reversal of orofacial hypersensitivity, supporting an important role of Cavα2δ1 in orofacial pain processing. Importantly, increased Cavα2δ1 in Vc/C2 superficial dorsal horn was associated with increased excitatory synaptogenesis and increased frequency, but not the amplitude, of miniature excitatory postsynaptic currents in dorsal horn neurons that could be blocked by gabapentin. Thus, CCI-ION-induced Cavα2δ1 up-regulation may contribute to orofacial neuropathic pain states through abnormal excitatory synapse formation and enhanced presynaptic excitatory neurotransmitter release in Vc/C2. PMID:24459143

  3. Evidence that nitric oxide may mediate the ovarian steroid-induced luteinizing hormone surge: involvement of excitatory amino acids.

    Science.gov (United States)

    Bonavera, J J; Sahu, A; Kalra, P S; Kalra, S P

    1993-12-01

    The involvement of excitatory N-methyl-D-aspartate (NMDA) receptors in the hypothalamic control of pituitary LH secretion is well recognized. Recent evidence shows that nitric oxide (NO), a free radical gas, may act as neurotransmitter in the brain, and its efflux is stimulated by activation of NMDA receptors. Studies were undertaken to determine whether NO is involved in the hypothalamic release of LHRH and in the LH surge induced by progesterone (P) in estrogen-primed ovariectomized rats. Rats were ovariectomized and 2 weeks later received estradiol benzoate (30 micrograms sc) at 1000 h. Two days later, P was injected at 1000 h to potentiate the estradiol benzoate-induced LH surge in the afternoon. Serial blood samples were collected at hourly intervals from 1400-1800 h via an intraatrial cannula implanted the day before P injection. Additionally, at various times before onset of the LH surge at 1400 h, the rats were injected sc with one of three inhibitors of NO synthase, the enzyme that generates NO. Control, saline-injected rats showed unambiguous LH surges in the afternoon. However, either a single injection at 1000 h of NG-methyl-L-arginine (20 mg/kg) or three injections at 1000, 1200, and 1400 h of either Nw-nitro-L-arginine methyl ester (NAME, 40 mg/kg) or Nw-nitro-L-arginine (60 mg/kg) to inhibit NO efflux markedly suppressed the P-induced LH surge in the afternoon. To ascertain whether suppression of LH surge was due to blockade of hypothalamic LHRH release, a series of in vitro studies were performed in steroid-primed rats. First we examined the effects of sodium nitroprusside (NPS), a compound that spontaneously generates and releases NO. NPS increased basal and KCl-induced LHRH release in vitro from the medial basal hypothalamus-preoptic area and median eminence fragments. No direct effect of NO at the pituitary level was seen, since NPS did not alter basal or LHRH-induced LH in vitro release from hemipituitaries. In addition, we tested the effects of

  4. Tracking the expression of excitatory and inhibitory neurotransmission-related proteins and neuroplasticity markers after noise induced hearing loss.

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    Cherylea J Browne

    Full Text Available Excessive exposure to loud noise can damage the cochlea and create a hearing loss. These pathologies coincide with a range of CNS changes including reorganisation of frequency representation, alterations in the pattern of spontaneous activity and changed expression of excitatory and inhibitory neurotransmitters. Moreover, damage to the cochlea is often accompanied by acoustic disorders such as hyperacusis and tinnitus, suggesting that one or more of these neuronal changes may be involved in these disorders, although the mechanisms remain unknown. We tested the hypothesis that excessive noise exposure increases expression of markers of excitation and plasticity, and decreases expression of inhibitory markers over a 32-day recovery period. Adult rats (n = 25 were monaurally exposed to a loud noise (16 kHz, 1/10(th octave band pass (115 dB SPL for 1-hour, or left as non-exposed controls (n = 5. Animals were euthanased at either 0, 4, 8, 16 or 32 days following acoustic trauma. We used Western Blots to quantify protein levels of GABA(A receptor subunit α1 (GABA(Aα1, Glutamic-Acid Decarboxylase-67 (GAD-67, N-Methyl-D-Aspartate receptor subunit 2A (NR2A, Calbindin (Calb1 and Growth Associated Protein 43 (GAP-43 in the Auditory Cortex (AC, Inferior Colliculus (IC and Dorsal Cochlear Nucleus (DCN. Compared to sham-exposed controls, noise-exposed animals had significantly (p<0.05: lower levels of GABA(Aα1 in the contralateral AC at day-16 and day-32, lower levels of GAD-67 in the ipsilateral DCN at day-4, lower levels of Calb1 in the ipsilateral DCN at day-0, lower levels of GABA(Aα1 in the ipsilateral AC at day-4 and day-32. GAP-43 was reduced in the ipsilateral AC for the duration of the experiment. These complex fluctuations in protein expression suggests that for at least a month following acoustic trauma the auditory system is adapting to a new pattern of sensory input.

  5. Evoked potentials and head injury. 1. Rating of evoked potential abnormality.

    Science.gov (United States)

    Rappaport, M; Hall, K; Hopkins, H K; Belleza, T

    1981-10-01

    This paper describes a method for rating the degree of abnormality of auditory, visual and somatosensory evoked potential patterns in head injury (HI) patients. Criteria for judging degree of EP abnormality are presented that allow assessment of the extent and severity of subcortical and cortical dysfunction associated with traumatic brain damage. Interrater reliability data based upon blind ratings of normal and HI patients are presented and shown to be highly significant. Tables of normative values of peak latencies and amplitudes are given and illustrations of EP patterns of different degrees of abnormality are presented.

  6. 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).

  7. Emissão otoacústica evocada transitória: instrumento para detecção precoce de alterações auditivas em recém-nascidos a termo e pré-termo Transient evoked otoacoustic emissions: tool for early detection of hearing alteration in full-term and preterm neonates

    Directory of Open Access Journals (Sweden)

    Cristiane Fregonesi Dutra Garcia

    2002-05-01

    early diagnostic and intervention in the hearing alterations are of fundamental importance in the infantile development. The register of the otoacoustic emissions has been enlargement indicated for being a fast exam, easily applied. Aim: The objectives of the present study were to value the peripheral hearing function of full term neonate and adequate and small preterm neonate for the gestacional age, by the research of the transient otoacoustic emissions, identifying the prevalence of hearing alterations in this population; to verify the influence from the variable gestacional ages and weight in the moment of the birth, as well as the kinds of treatment, mechanics ventilations, administration of ototoxicity medicines and the permanence in the incubator and to analyze the factors that interfere in the programs of neonatal hearing screening. Study design: Clinical prospective. Material and method: There were appraised 157 children, whose 43 were born full term, 79 preterm adequate to gestacional age and 35 small preterm to gestacional age. It had been observed that premature neonates fail more in the answers from otoacoustic emissions. Results: The prevalence of conductive hearing impairment in the population studied was from 29 ears to 1000 and for the sensory-neural hearing impairment from the 16 to 1000. The low weight children in the birth were the most difficult to be appraised. The transient otoacoustic emissions were observed from the beginning of 27 gestacional weeks old. The kinds of treatments used were factors that influenced negatively in the answers of the otoacoustic emissions in premature groups. Conclusion: The early diagnostic work of the hearing impairment must be objective of the interdisciplinary team -- neonatologist, pediatrician, ear/nose and throat doctor, audiologist and speech-language pathologist, nurse and relatives -- and must be followed, immediately, by the early interventions programs.

  8. 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.

  9. Distraction Reduces Both Early and Late Electrocutaneous Stimulus Evoked Potentials

    NARCIS (Netherlands)

    Blom, J.H.G.; Wiering, Caro H.; van der Lubbe, Robert Henricus Johannes

    2012-01-01

    Previous electroencephalography studies revealed mixed effects of sustained distraction on early negative and later positive event-related potential components evoked by electrocutaneous stimuli. In our study we further examined the influence of sustained distraction to clarify these discrepancies.

  10. Click-evoked responses in vestibular afferents in rats

    National Research Council Canada - National Science Library

    Zhu, Hong; Tang, Xuehui; Wei, Wei; Mustain, William; Xu, Youguo; Zhou, Wu

    2011-01-01

    Sound activates not only the cochlea but also the vestibular end organs. Research on this phenomenon led to the discovery of the sound-evoked vestibular myogenic potentials recorded from the sternocleidomastoid muscles...

  11. Agonist-Evoked Ca2+ Signaling in Enteric Glia Drives Neural Programs That Regulate Intestinal Motility in MiceSummary

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    Jonathon L. McClain

    2015-11-01

    Full Text Available Background & Aims: Gastrointestinal motility is regulated by enteric neural circuitry that includes enteric neurons and glia. Enteric glia monitor synaptic activity and exhibit responses to neurotransmitters that are encoded by intracellular calcium (Ca2+ signaling. What role evoked glial responses play in the neural regulation of gut motility is unknown. We tested how evoking Ca2+ signaling in enteric glia affects the neural control of intestinal motility. Methods: We used a novel chemogenetic mouse model that expresses the designer receptor hM3Dq under the transcriptional control of the glial fibrillary acidic protein (GFAP promoter (GFAP::hM3Dq mice to selectively trigger glial Ca2+ signaling. We used in situ Ca2+ imaging and immunohistochemistry to validate this model, and we assessed gut motility by measuring pellet output and composition, colonic bead expulsion time, small intestinal transit time, total gut transit time, colonic migrating motor complex (CMMC recordings, and muscle tension recordings. Results: Expression of the hM3Dq receptor is confined to GFAP-positive enteric glia in the intestines of GFAP::hM3Dq mice. In these mice, application of the hM3Dq agonist clozapine-N-oxide (CNO selectively triggers intracellular Ca2+ responses in enteric glia. Glial activation drove neurogenic contractions in the ileum and colon but had no effect on neurogenic relaxations. CNO enhanced the amplitude and frequency of CMMCs in ex vivo preparations of the colon, and CNO increased colonic motility in vivo. CNO had no effect on the composition of fecal matter, small intestinal transit, or whole gut transit. Conclusions: Glial excitability encoded by intracellular Ca2+ signaling functions to modulate excitatory enteric circuits. Selectively triggering glial Ca2+ signaling might be a novel strategy to improve gut function in motility disorders. Keywords: Autonomic, Chemogenetic, Enteric Nervous System, Intestine, Gut

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

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    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

  13. Effects of isoflurane and desflurane on neurogenic motor- and somatosensory-evoked potential monitoring for scoliosis surgery.

    Science.gov (United States)

    Bernard, J M; Péréon, Y; Fayet, G; Guihéneuc, P

    1996-11-01

    -to-peak amplitude of this wave was not significantly altered with isoflurane and desflurane, either in the presence or in the absence of nitrous oxide. Compared with cortical somatosensory-evoked potentials, neurogenic motor-evoked potential signals are well preserved in patients undergoing surgery to correct scoliosis under general anesthesia supplemented with isoflurane or desflurane in concentrations as great as 1 MAC.

  14. Excitatory actions of GABA in developing chick vestibular afferents: effects on resting electrical activity.

    Science.gov (United States)

    Cortes, Celso; Galindo, Fabian; Galicia, Salvador; Cebada, Jorge; Flores, Amira

    2013-07-01

    The aim of this study was to characterize the effect of γ-aminobutyric acid (GABA) in the resting multiunit activity of the vestibular afferents during development using the isolated inner ear of embryonic and postnatal chickens (E15-E21 and P5). GABA (10(-3) to 10(-5) M; n = 133) and muscimol (10(-3) M) elicited an increase in the frequency of the basal discharge of the vestibular afferents. We found that GABA action was dose-dependent and inversely related to animal age. Thus, the largest effect was observed in embryonic ages such as E15 and E17 and decreases in E21 and P5. The GABAA receptor antagonists, bicuculline (10(-5) M; n = 10) and picrotoxin (10(-4) M; n = 10), significantly decreased the excitatory action of GABA and muscimol (10(-3) M). Additionally, CNQX 10(-6) M, MCPG 10(-5) M and 7ClKyn 10(-5) M (n = 5) were co-applied by bath substitution (n = 5). Both the basal discharge and the GABA action significantly decreased in these experimental conditions. The chloride channel blocker 9-AC 0.5 mM produced an important reduction in the effect of GABA 10(-3) (n = 5) and 10(-4) M (n = 5). Thus, our results suggest an excitatory role of GABA in the resting activity of the vestibular afferents that can be explained by changes in the gradient of concentration of Cl(-) during development. We show for the first time that the magnitude of this GABA effect decreases at later stages of embryonic and early postnatal development. Taking into account the results with glutamatergic antagonists, we conclude that GABA has a presynaptic action but is not the neurotransmitter in the vestibular afferent synapses, although it could act as a facilitator of the spontaneous activity and may regulate glutamate release. Copyright © 2013 Wiley Periodicals, Inc.

  15. Postsynaptic mechanisms underlying the excitatory action of histamine on medial vestibular nucleus neurons in rats

    Science.gov (United States)

    Zhang, Xiao-Yang; Yu, Lei; Zhuang, Qian-Xing; Peng, Shi-Yu; Zhu, Jing-Ning; Wang, Jian-Jun

    2013-01-01

    Background and Purpose Anti-histaminergic drugs have been widely used in the clinical treatment of vestibular disorders and most studies concentrate on their presynaptic actions. The present study investigated the postsynaptic effect of histamine on medial vestibular nucleus (MVN) neurons and the underlying mechanisms. Experimental Approach Histamine-induced postsynaptic actions on MVN neurons and the corresponding receptor and ionic mechanisms were detected by whole-cell patch-clamp recordings on rat brain slices. The distribution of postsynaptic histamine H1, H2 and H4 receptors was mapped by double and single immunostaining. Furthermore, the expression of mRNAs for H1, H2 and H4 receptors and for subtypes of Na+–Ca2+ exchangers (NCXs) and hyperpolarization-activated cyclic nucleotide-gated (HCN) channels was assessed by quantitative real-time RT-PCR. Key Results A marked postsynaptic excitatory effect, co-mediated by histamine H1 and H2 receptors, was involved in the histamine-induced depolarization of MVN neurons. Postsynaptic H1 and H2 rather than H4 receptors were co-localized in the same MVN neurons. NCXs contributed to the inward current mediated by H1 receptors, whereas HCN channels were responsible for excitation induced by activation of H2 receptors. Moreover, NCX1 and NCX3 rather than NCX2, and HCN1 rather than HCN2-4 mRNAs, were abundantly expressed in MVN. Conclusion and Implications NCXs coupled to H1 receptors and HCN channels linked to H2 receptors co-mediate the strong postsynaptic excitatory action of histamine on MVN neurons. These results highlight an active role of postsynaptic mechanisms in the modulation by central histaminergic systems of vestibular functions and suggest potential targets for clinical treatment of vestibular disorders. Linked Articles This article is part of a themed issue on Histamine Pharmacology Update. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2013.170.issue-1 PMID:23713466

  16. Flash visual evoked potentials in preterm infants.

    Science.gov (United States)

    Feng, Jing-Jing; Wang, Wei-Ping; Guo, Shu-Juan; Liu, Zhi-Wei; Xu, Xiu

    2013-03-01

    To describe the development of flash visual evoked potentials (FVEPs) in preterm infants from 1 to 18 months and to determine if the maturation of FVEPs is similar to that of term infants. Longitudinal follow-up study. Twenty very low birth weight (VLBW) preterm infants, 42 low birth weight (LBW) preterm infants, and 41 term infants underwent FVEP recordings and neurodevelopmental examinations at 1, 3, 6, 9, 12, and 18 months of corrected and chronological ages. The FVEP recordings were carried out with the VikingQuest-IV neuroelectrophysiological device (VikingQuest, Nicolet, WI), and neurodevelopmental assessments were made by the Development Screen Test and Bayley Scales of Infant Development, Second Edition. At 1, 3, 6, and 9 months of age, neurodevelopment was measured with the Mental Index and Developmental Quotient. At 12 and 18 months, neurodevelopment was assessed using the Mental Developmental Index and Psychomotor Developmental Index. Two FVEP values were analyzed: the P2 amplitude (peak to peak from the preceding N2 wave) and the latency of the P2 wave. There was no significant difference for age-dependent decreased pattern of FVEP P2 latency between preterm infants and the control group. This pattern consisted of a rapid decrease in the first 6 months of life, a gradual decline from 6 to 12 months of age, and a steady reduction from 12 to 18 months of age. The P2 latencies were prolonged significantly at all 6 recorded times in the VLBW group compared with the controls and showed a delay in the LBW group at 1 and 3 months of corrected age. The maturation of P2 latency in LBW infants is similar to that of the controls at 3 months of corrected age, but the maturation of P2 latency in VLBW children remained delayed when compared with the controls until 18 months of corrected age. Although the FVEP development pattern of preterm infants was similar to that of healthy full-term infants, the former had deficits in visual electrophysiologic maturation

  17. 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.

  18. Somatodendritic and excitatory postsynaptic distribution of neuron-type dystrophin isoform, Dp40, in hippocampal neurons.

    Science.gov (United States)

    Fujimoto, Takahiro; Itoh, Kyoko; Yaoi, Takeshi; Fushiki, Shinji

    2014-09-12

    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 NH2-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. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Coupling-induced population synchronization in an excitatory population of subthreshold Izhikevich neurons.

    Science.gov (United States)

    Kim, Sang-Yoon; Lim, Woochang

    2013-12-01

    We consider an excitatory population of subthreshold Izhikevich neurons which exhibit noise-induced firings. By varying the coupling strength J, we investigate population synchronization between the noise-induced firings which may be used for efficient cognitive processing such as sensory perception, multisensory binding, selective attention, and memory formation. As J is increased, rich types of population synchronization (e.g., spike, burst, and fast spike synchronization) are found to occur. Transitions between population synchronization and incoherence are well described in terms of an order parameter [Formula: see text]. As a final step, the coupling induces oscillator death (quenching of noise-induced spikings) because each neuron is attracted to a noisy equilibrium state. The oscillator death leads to a transition from firing to non-firing states at the population level, which may be well described in terms of the time-averaged population spike rate [Formula: see text]. In addition to the statistical-mechanical analysis using [Formula: see text] and [Formula: see text], each population and individual state are also characterized by using the techniques of nonlinear dynamics such as the raster plot of neural spikes, the time series of the membrane potential, and the phase portrait. We note that population synchronization of noise-induced firings may lead to emergence of synchronous brain rhythms in a noisy environment, associated with diverse cognitive functions.

  20. The relative contribution of NMDARs to excitatory postsynaptic currents is controlled by Ca2+-induced inactivation.

    Directory of Open Access Journals (Sweden)

    Fliza eValiullina

    2016-01-01

    Full Text Available NMDA receptors (NMDARs are important mediators of excitatory synaptic transmission and plasticity. A hallmark of these channels is their high permeability to Ca2+. At the same time, they are themselves inhibited by the elevation of intracellular Ca2+ concentration. It is unclear however, whether the Ca2+ entry associated with single NMDAR mediated synaptic events is sufficient to self-inhibit their activation. Such auto-regulation would have important effects on the dynamics of synaptic excitation in several central networks. Therefore, we studied NMDAR-mediated synaptic currents in mouse hippocampal CA1 pyramidal neurons. Postsynaptic responses to subthreshold Schaffer collateral stimulation depended strongly on the absence or presence of intracellular Ca2+ buffers. Loading of pyramidal cells with exogenous Ca2+ buffers increased the amplitude and decay time of NMDAR mediated EPSCs (EPSP and prolonged the time window for action potential generation.Our data indicate that the Ca2+ influx mediated by unitary synaptic events is sufficient to produce detectable self-inhibition of NMDARs even at a physiological Mg2+ concentration. Therefore, the contribution of NMDARs to synaptic excitation is strongly controlled by both previous synaptic activity as well as by the Ca2+ buffer capacity of postsynaptic neurons.

  1. A family of excitatory peptide toxins from venomous crassispirine snails: using Constellation Pharmacology to assess bioactivity.

    Science.gov (United States)

    Imperial, Julita S; Cabang, April B; Song, Jie; Raghuraman, Shrinivasan; Gajewiak, Joanna; Watkins, Maren; Showers-Corneli, Patrice; Fedosov, Alexander; Concepcion, Gisela P; Terlau, Heinrich; Teichert, Russell W; Olivera, Baldomero M

    2014-10-01

    The toxinology of the crassispirine snails, a major group of venomous marine gastropods within the superfamily Conoidea, is largely unknown. Here we define the first venom peptide superfamily, the P-like crassipeptides, and show that the organization of their gene sequences is similar to conotoxin precursors. We provide evidence that one peptide family within the P-like crassipeptide superfamily includes potassium-channel (K-channel) blockers, the κP-crassipeptides. Three of these peptides were chemically synthesized (cce9a, cce9b and iqi9a). Using conventional electrophysiology, cce9b was shown to be an antagonist of both a human Kv1.1 channel isoform (Shaker subfamily of voltage-gated K channels) and a Drosophila K-channel isoform. We assessed the bioactivity of these peptides in native mammalian dorsal root ganglion neurons in culture. We demonstrate that two of these crassipeptides, cce9a and cce9b, elicited an excitatory phenotype in a subset of small-diameter capsaicin-sensitive mouse DRG neurons that were also affected by κJ-conotoxin PlXIVA (pl14a), a blocker of Kv1.6 channels. Given the vast complexity of heteromeric K-channel isoforms, this study demonstrates that the crassispirine venoms are a potentially rich source for discovering novel peptides that can help to identify and characterize the diversity of K-channel subtypes expressed in native neurons and other cell types. Published by Elsevier Ltd.

  2. Designing Novel Nanoformulations Targeting Glutamate Transporter Excitatory Amino Acid Transporter 2: Implications in Treating Drug Addiction.

    Science.gov (United States)

    Rao, Pss; Yallapu, Murali M; Sari, Youssef; Fisher, Paul B; Kumar, Santosh

    Chronic drug abuse is associated with elevated extracellular glutamate concentration in the brain reward regions. Deficit of glutamate clearance has been identified as a contributing factor that leads to enhanced glutamate concentration following extended drug abuse. Importantly, normalization of glutamate level through induction of glutamate transporter 1 (GLT1)/ excitatory amino acid transporter 2 (EAAT2) expression has been described in several in vivo studies. GLT1 upregulators including ceftriaxone, a beta-lactam antibiotic, have been effective in attenuating drug-seeking and drug-consumption behavior in rodent models. However, potential obstacles toward clinical translation of GLT1 (EAAT2) upregulators as treatment for drug addiction might include poor gastrointestinal absorption, serious peripheral adverse effects, and/or suboptimal CNS concentrations. Given the growing success of nanotechnology in targeting CNS ailments, nanoformulating known GLT1 (EAAT2) upregulators for selective uptake across the blood brain barrier presents an ideal therapeutic approach for treating drug addiction. In this review, we summarize the results obtained with promising GLT1 (EAAT2) inducing compounds in animal models recapitulating drug addiction. Additionally, the various nanoformulations that can be employed for selectively increasing the CNS bioavailability of GLT1 (EAAT2) upregulators are discussed. Finally, the applicability of GLT1 (EAAT2) induction via central delivery of drug-loaded nanoformulations is described.

  3. Common circuit defect of excitatory-inhibitory balance in mouse models of autism.

    Science.gov (United States)

    Gogolla, Nadine; Leblanc, Jocelyn J; Quast, Kathleen B; Südhof, Thomas C; Fagiolini, Michela; Hensch, Takao K

    2009-06-01

    One unifying explanation for the complexity of Autism Spectrum Disorders (ASD) may lie in the disruption of excitatory/inhibitory (E/I) circuit balance during critical periods of development. We examined whether Parvalbumin (PV)-positive inhibitory neurons, which normally drive experience-dependent circuit refinement (Hensch Nat Rev Neurosci 6:877-888, 1), are disrupted across heterogeneous ASD mouse models. We performed a meta-analysis of PV expression in previously published ASD mouse models and analyzed two additional models, reflecting an embryonic chemical insult (prenatal valproate, VPA) or single-gene mutation identified in human patients (Neuroligin-3, NL-3 R451C). PV-cells were reduced in the neocortex across multiple ASD mouse models. In striking contrast to controls, both VPA and NL-3 mouse models exhibited an asymmetric PV-cell reduction across hemispheres in parietal and occipital cortices (but not the underlying area CA1). ASD mouse models may share a PV-circuit disruption, providing new insight into circuit development and potential prevention by treatment of autism. The online version of this article (doi:10.1007/s11689-009-9023-x) contains supplementary material, which is available to authorized users.

  4. APP Homodimers Transduce an Amyloid-β-Mediated Increase in Release Probability at Excitatory Synapses

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    Hilla Fogel

    2014-06-01

    Full Text Available Accumulation of amyloid-β peptides (Aβ, the proteolytic products of the amyloid precursor protein (APP, induces a variety of synaptic dysfunctions ranging from hyperactivity to depression that are thought to cause cognitive decline in Alzheimer’s disease. While depression of synaptic transmission has been extensively studied, the mechanisms underlying synaptic hyperactivity remain unknown. Here, we show that Aβ40 monomers and dimers augment release probability through local fine-tuning of APP-APP interactions at excitatory hippocampal boutons. Aβ40 binds to the APP, increases the APP homodimer fraction at the plasma membrane, and promotes APP-APP interactions. The APP activation induces structural rearrangements in the APP/Gi/o-protein complex, boosting presynaptic calcium flux and vesicle release. The APP growth-factor-like domain (GFLD mediates APP-APP conformational changes and presynaptic enhancement. Thus, the APP homodimer constitutes a presynaptic receptor that transduces signal from Aβ40 to glutamate release. Excessive APP activation may initiate a positive feedback loop, contributing to hippocampal hyperactivity in Alzheimer’s disease.

  5. [Ischemic Stroke, Excitatory Amino Acids Toxicity and the Adjustment of Acupuncture Intervention].

    Science.gov (United States)

    Li, Xiao-xiao; Lu, Sheng-feng; Zhu, Bing-mei; Fu, Shu-ping

    2016-04-01

    Excitatory amino acids toxicity is an onset causation of cerebral ischemia injury cascade reaction, and eventually leading to brain cell necrosis and apoptosis. Acupuncture is reported to be effective for ischemic stroke in clinical practice and animal experiments, but its mechanism is still under exploring. In this paper the authors introduce the research status of antiexcitatory amino acids toxicity effect of acupuncture in ischemic stroke animals by summarizing its effects on subunits of ionotropic glutamate receptor (NMDA/AMPA) and metabotropic glutamate receptors (mGluRs), and on astrocyte activities. Results indicated that acupuncture intervention may down-regulate the expression levels of cerebral multi-types (NR 1, NR 2 B) of glutamate NMDA receptors, up-regulate expression of glutamate transporter-1, NR 2 A, cannabinoid receptor (CBR) type 1 and 2, and suppress activities of cerebral astrocytes, reduce the content of extracellular glutamate to lower its toxicity and to improve stroke at last. The present paper may provide a reference for acupuncture research on ischemic brain injury.

  6. Beyond blow-up in excitatory integrate and fire neuronal networks: Refractory period and spontaneous activity.

    Science.gov (United States)

    Cáceres, María J; Perthame, Benoît

    2014-06-07

    The Network Noisy Leaky Integrate and Fire equation is among the simplest model allowing for a self-consistent description of neural networks and gives a rule to determine the probability to find a neuron at the potential v. However, its mathematical structure is still poorly understood and, concerning its solutions, very few results are available. In the midst of them, a recent result shows blow-up in finite time for fully excitatory networks. The intuitive explanation is that each firing neuron induces a discharge of the others; thus increases the activity and consequently the discharge rate of the full network. In order to better understand the details of the phenomena and show that the equation is more complex and fruitful than expected, we analyze further the model. We extend the finite time blow-up result to the case when neurons, after firing, enter a refractory state for a given period of time. We also show that spontaneous activity may occur when, additionally, randomness is included on the firing potential VF in regimes where blow-up occurs for a fixed value of VF. Copyright © 2014 Elsevier Ltd. All rights reserved.

  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. 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.

  9. Sex-Specific Automatic Responses to Infant Cries: TMS Reveals Greater Excitability in Females than Males in Motor Evoked Potentials.

    Science.gov (United States)

    Messina, Irene; Cattaneo, Luigi; Venuti, Paola; de Pisapia, Nicola; Serra, Mauro; Esposito, Gianluca; Rigo, Paola; Farneti, Alessandra; Bornstein, Marc H

    2015-01-01

    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 after 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 infant cry specific to females and to the ID1 muscle. We regard this modulation as a response to natural cry sounds because it was attenuated to stimuli increasingly different from natural cry and 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 response 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.

  10. Effects of ketamine and propofol on motor evoked potentials elicited by intracranial microstimulation during deep brain stimulation

    Directory of Open Access Journals (Sweden)

    Havan eFurmaga

    2014-05-01

    Full Text Available Few preclinical or clinical studies have evaluated the effect of anesthetics on motor evoked potentials (MEPs, either alone or in the presence of conditioning stimuli such as deep brain stimulation (DBS. In this study we evaluated the effect of two commonly used anesthetic agents, propofol and ketamine, on MEPs elicited by intra-cortical microstimulation of the motor cortex in a rodent model with and without DBS of the dentatothalamocortical (DTC pathway. The effects of propofol anesthesia on MEP amplitudes during DTC DBS were found to be highly dose dependent. Standard-, but not high-, dose propofol potentiated the facilitatory effects of 30 Hz DTC DBS on MEPs. This facilitation was sustained and phase-dependent, indicating that, compared to high dose propofol, standard dose propofol has a beta-band excitatory effect on cortical networks. In contrast, ketamine anesthetic demonstrated a monotonic relationship with increasing frequencies of stimulation, such that the highest frequency of stimulation resulted in the greatest MEP amplitude. Ketamine also showed phase dependency but less pronounced than standard dose propofol. The results underscore the importance of better understanding the complex effects of anesthetics on cortical networks and exogenous stimuli. Choice of anesthetic agents and dosing may significantly confound or even skew research outcomes, including experimentation in novel DBS indications and paradigms.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. Different neuropeptides are expressed in different functional subsets of cholinergic excitatory motorneurons in the nematode Ascaris suum.

    Science.gov (United States)

    Konop, Christopher J; Knickelbine, Jennifer J; Sygulla, Molly S; Vestling, Martha M; Stretton, Antony O W

    2015-06-17

    Neuropeptides are known to have dramatic effects on neurons and synapses; however, despite extensive studies of the motorneurons in the parasitic nematode Ascaris suum, their peptide content had not yet been described. We determined the peptide content of single excitatory motorneurons by mass spectrometry and tandem mass spectrometry. There are two subsets of ventral cord excitatory motorneurons, each with neuromuscular output either anterior or posterior to their cell body, mediating forward or backward locomotion, respectively. Strikingly, the two sets of neurons contain different neuropeptides, with AF9 and six novel peptides (As-NLP-21.1-6) in anterior projectors, and the six afp-1 peptides in addition to AF2 in posterior projectors. In situ hybridization confirmed the expression of these peptides, validating the integrity of the dissection technique. This work identifies new components of the functional behavioral circuit, as well as potential targets for antiparasitic drug development.

  16. ELKS controls the pool of readily releasable vesicles at excitatory synapses through its N-terminal coiled-coil domains.

    Science.gov (United States)

    Held, Richard G; Liu, Changliang; Kaeser, Pascal S

    2016-06-02

    In a presynaptic nerve terminal, synaptic strength is determined by the pool of readily releasable vesicles (RRP) and the probability of release (P) of each RRP vesicle. These parameters are controlled at the active zone and vary across synapses, but how such synapse specific control is achieved is not understood. ELKS proteins are enriched at vertebrate active zones and enhance P at inhibitory hippocampal synapses, but ELKS functions at excitatory synapses are not known. Studying conditional knockout mice for ELKS, we find that ELKS enhances the RRP at excitatory synapses without affecting P. Surprisingly, ELKS C-terminal sequences, which interact with RIM, are dispensable for RRP enhancement. Instead, the N-terminal ELKS coiled-coil domains that bind to Liprin-α and Bassoon are necessary to control RRP. Thus, ELKS removal has differential, synapse-specific effects on RRP and P, and our findings establish important roles for ELKS N-terminal domains in synaptic vesicle priming.

  17. Splicing-Dependent Trans-synaptic SALM3–LAR-RPTP Interactions Regulate Excitatory Synapse Development and Locomotion

    Directory of Open Access Journals (Sweden)

    Yan Li

    2015-09-01

    Full Text Available Synaptic adhesion molecules regulate diverse aspects of synapse development and plasticity. SALM3 is a PSD-95-interacting synaptic adhesion molecule known to induce presynaptic differentiation in contacting axons, but little is known about its presynaptic receptors and in vivo functions. Here, we identify an interaction between SALM3 and LAR family receptor protein tyrosine phosphatases (LAR-RPTPs that requires the mini-exon B splice insert in LAR-RPTPs. In addition, SALM3-dependent presynaptic differentiation requires all three types of LAR-RPTPs. SALM3 mutant (Salm3−/− mice display markedly reduced excitatory synapse number but normal synaptic plasticity in the hippocampal CA1 region. Salm3−/− mice exhibit hypoactivity in both novel and familiar environments but perform normally in learning and memory tests administered. These results suggest that SALM3 regulates excitatory synapse development and locomotion behavior.

  18. Effect of pelvic floor muscle contraction on vesical and rectal function with identification of puborectalis-rectovesical inhibitory reflex and levator-rectovesical excitatory reflex.

    Science.gov (United States)

    Shafik, A; El-Sibai, O

    2001-08-01

    changes. Repetition of the test using saline instead of xylocaine resulted in rectal and vesical pressure responses similar to those without the use of saline. In conclusion, the decline in rectal and vesical responses upon PR muscle contraction indicates a reflex relationship which we term 'puborectalis rectovesical inhibitory reflex'. This reflex is suggested to abort the urge to defecate or urinate. In contrast, LA muscle contraction produced rectal and vesical pressure elevation which is suggested to be mediated through the 'levator rectovesical excitatory reflex'. 'This reflex is probably evoked to promote rectal and vesical evacuation.

  19. β2-Adrenergic Receptor Activation Suppresses the Rat Phenethylamine Hallucinogen-Induced Head Twitch Response: Hallucinogen-Induced Excitatory Post-synaptic Potentials as a Potential Substrate

    Directory of Open Access Journals (Sweden)

    Gerard J. Marek

    2018-02-01

    Full Text Available 5-Hydroxytryptamine2A (5-HT2A receptors are enriched in layers I and Va of the rat prefrontal cortex and neocortex and their activation increases the frequency of glutamatergic excitatory post-synaptic potentials/currents (EPSP/Cs onto layer V pyramidal cells. A number of other G-protein coupled receptors (GPCRs are also enriched in cortical layers I and Va and either induce (α1-adrenergic and orexin2 or suppress (metabotropic glutamate2 [mGlu2], adenosine A1, μ-opioid both 5-HT-induced EPSCs and head twitches or head shakes induced by the phenethylamine hallucinogen 2,5-dimethoxy-4-iodoamphetamine (DOI. Another neurotransmitter receptor also localized to apparent thalamocortical afferents to layers I and Va of the rat prefrontal cortex and neocortex is the β2-adrenergic receptor. Therefore, we conducted preliminary electrophysiological experiments with rat brain slices examining the effects of epinephrine on electrically-evoked EPSPs following bath application of DOI (3 μM. Epinephrine (0.3–10 μM suppressed the late EPSPs produced by electrical stimulation and DOI. The selective β2-adrenergic receptor antagonist ICI-118,551 (300 nM resulted in a rightward shift of the epinephrine concentration-response relationship. We also tested the selective β2-adrenergic receptor agonist clenbuterol and the antagonist ICI-118,551 on DOI-induced head twitches. Clenbuterol (0.3–3 mg/kg, i.p. suppressed DOI (1.25 mg/kg, i.p.-induced head twitches. This clenbuterol effect appeared to be at least partially reversed by the selective β2-adrenergic receptor antagonist ICI-118,553 (0.01–1 mg/kg, i.p., with significant reversal at doses of 0.1 and 1 mg/kg. Thus, β2-adrenergic receptor activation reverses the effects of phenethylamine hallucinogens in the rat prefrontal cortex. While Gi/Go-coupled GPCRs have previously been shown to suppress both the electrophysiological and behavioral effects of 5-HT2A receptor activation in the mPFC, the present work

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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.

  2. Circuits that Innervate Excitatory-Inhibitory Cells in the Inferior Colliculus Obtained with In-Vivo Whole Cell Recordings

    Science.gov (United States)

    Li, Na; Pollak, George D.

    2013-01-01

    Neurons excited by stimulation of one ear and suppressed by the other, called EI neurons, are sensitive to interaural intensity disparities (IIDs), the cues animals use to localize high frequencies. EI neurons are first formed in lateral superior olive (LSO), which then sends excitatory projections to the dorsal nucleus of the lateral lemniscus (DNLL) and the inferior colliculus (IC), both of which contain large populations of EI cells. We evaluate the inputs that innervate EI cells in the IC of Mexican free-tailed bats, Tadarida brasilensis mexicana, with in vivo whole cell recordings from which we derived excitatory and inhibitory conductances. We show that the basic EI property in the majority of IC cells is inherited from LSO, but each type of EI cell is also innervated by the ipsi- or contralateral DNLL, as well as additional excitatory and inhibitory inputs from monaural nuclei. We identify three EI types, where each type receives a set of projections that are different from the other types. To evaluate the role that the various projections played in generating binaural responses, we used modeling to compute a predicted response from the conductances. We then omitted one of the conductances from the computation to evaluate the degree to which that input contributed to the binaural response. We show that formation of the EI property in the various types is complex, and that some projections exert such subtle influences that they could not have been detected with extracellular recordings or even from intracellular recordings of post-synaptic potentials. PMID:23575835

  3. Preferential labeling of inhibitory and excitatory cortical neurons by endogenous tropism of adeno-associated virus and lentivirus vectors.

    Science.gov (United States)

    Nathanson, J L; Yanagawa, Y; Obata, K; Callaway, E M

    2009-06-30

    Despite increasingly widespread use of recombinant adeno-associated virus (AAV) and lentiviral (LV) vectors for transduction of neurons in a wide range of brain structures and species, the diversity of cell types within a given brain structure is rarely considered. For example, the ability of a vector to transduce neurons within a brain structure is often assumed to indicate that all neuron types within the structure are transduced. We have characterized the transduction of mouse somatosensory cortical neuron types by recombinant AAV pseudotyped with serotype 1 capsid (rAAV2/1) and by recombinant lentivirus pseudotyped with the vesicular stomatitis virus (VSV) glycoprotein. Both vectors used human synapsin (hSyn) promoter driving DsRed-Express. We demonstrate that high titer rAAV2/1-hSyn efficiently transduces both cortical excitatory and inhibitory neuronal populations, but use of lower titers exposes a strong preference for transduction of cortical inhibitory neurons and layer 5 pyramidal neurons. In contrast, we find that VSV-G-LV-hSyn principally labels excitatory cortical neurons at the highest viral titer generated. These findings demonstrate that endogenous tropism of rAAV2/1 and VSV-G-LV can be used to obtain preferential gene expression in mouse somatosensory cortical inhibitory and excitatory neuron populations, respectively.

  4. Repetitive magnetic stimulation induces plasticity of excitatory postsynapses on proximal dendrites of cultured mouse CA1 pyramidal neurons.

    Science.gov (United States)

    Lenz, Maximilian; Platschek, Steffen; Priesemann, Viola; Becker, Denise; Willems, Laurent M; Ziemann, Ulf; Deller, Thomas; Müller-Dahlhaus, Florian; Jedlicka, Peter; Vlachos, Andreas

    2015-11-01

    Repetitive transcranial magnetic stimulation (rTMS) of the human brain can lead to long-lasting changes in cortical excitability. However, the cellular and molecular mechanisms which underlie rTMS-induced plasticity remain incompletely understood. Here, we used repetitive magnetic stimulation (rMS) of mouse entorhino-hippocampal slice cultures to study rMS-induced plasticity of excitatory postsynapses. By employing whole-cell patch-clamp recordings of CA1 pyramidal neurons, local electrical stimulations, immunostainings for the glutamate receptor subunit GluA1 and compartmental modeling, we found evidence for a preferential potentiation of excitatory synapses on proximal dendrites of CA1 neurons (2-4 h after stimulation). This rMS-induced synaptic potentiation required the activation of voltage-gated sodium channels, L-type voltage-gated calcium channels and N-methyl-D-aspartate-receptors. In view of these findings we propose a cellular model for the preferential strengthening of excitatory synapses on proximal dendrites following rMS in vitro, which is based on a cooperative effect of synaptic glutamatergic transmission and postsynaptic depolarization.

  5. 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

    Spinal neuronal networks are essential for motor function. They are involved in the integration of sensory inputs and the generation of rhythmic motor outputs. They continuously adapt their activity to the internal state of the organism and to the environment. This plasticity can be provided...... 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...... by releasing gliotransmitters, which in turn modulate synaptic transmission. Here we investigated if astrocytes present in the ventral horn of the spinal cord modulate synaptic transmission. We evoked synaptic inputs in ventral horn neurons recorded in a slice preparation from the spinal cord of neonatal mice...

  6. Cerebroprotective activity of U-50488H: Relationship to interactions with excitatory amino acids and calcium

    Energy Technology Data Exchange (ETDEWEB)

    Camacho Ochoa, M.

    1987-01-01

    The mechanism underlying the anticonvulsant and cerebroprotective activity of U-50488H was evaluated using {sup 45}Ca{sup ++} uptake in rat Ficoll purified synaptosomes, ({sup 3}H)-2-deoxyglucose uptake in selected mouse brain regions, ({sup 3}H)kainic acid binding to mouse forebrain synaptic membranes and incidence of KA-induced lesions in the CA3 region of the mouse hippocampus. U-50488H causes reduction in K{sup +}-evoked {sup 45}Ca{sup ++} uptake. These effects are comparable to those of the calcium channel blockers verapamil and nifedipine and seem to be related to calcium dependent mechanisms. Changes in saturability, specificity and dissociation constant values of kainic acid receptor binding were demonstrated in the presence of U-50488H at concentrations similar to those used in {sup 45}Ca{sup ++} uptake studies and in the presence of calcium and chloride ions.

  7. Advanced Glycation-Modified Human Serum Albumin Evokes Alterations in Membrane and Eryptosis in Erythrocytes.

    Science.gov (United States)

    Awasthi, Saurabh; Gayathiri, S K; Ramya, R; Duraichelvan, R; Dhason, A; Saraswathi, N T

    2015-11-01

    Increased burden of advanced glycation end-products (AGEs) in case of hyperglycemic conditions leads to the development of retinopathy, nephropathy, and cardiovascular and neurological disorders such as Alzheimer's disease. AGEs are considered as pro-oxidants, and their accumulation increases the oxidative stress. The prolonged exposure to these AGEs is the fundamental cause of chronic oxidative stress. Abnormal morphology of red blood cells (RBCs) and excessive eryptosis has been observed in diabetes, glomerulonephritis, dyslipidemia, and obesity, but yet the contribution of extracellular AGEs remains undefined. In this study, we investigated the effect of AGEs on erythrocytes to determine their impact on the occurrence of different pathological forms of these blood cells. Specifically, carboxymethyllysine (CML), carboxyethyllysine (CEL), and Arg-pyrimidine (Arg-P) which have been reported to be the most pre-dominant AGEs formed under in vivo conditions were used in this study. Results suggested the eryptotic properties of CML, CEL, and Arg-P for RBCs, which were evident from the highly damaged cell membrane and occurrence of abnormal morphologies. Methylglyoxal-modified albumin showed more severe effects, which can be attributed to the high reactivity and pro-oxidant nature of glycation end products. These findings suggest the possible role of AGE-modified albumin towards the morphological changes in erythrocyte's membrane associated with diabetic conditions.

  8. Cannabinoid CB1 receptor calibrates excitatory synaptic balance in the mouse hippocampus.

    Science.gov (United States)

    Monory, Krisztina; Polack, Martin; Remus, Anita; Lutz, Beat; Korte, Martin

    2015-03-04

    The endocannabinoid system negatively regulates the release of various neurotransmitters in an activity-dependent manner, thereby influencing the excitability of neuronal circuits. In the hippocampus, cannabinoid type 1 (CB1) receptor is present on both GABAergic and glutamatergic axon terminals. CB1 receptor-deficient mice were previously shown to have increased hippocampal long-term potentiation (LTP). In this study, we have investigated the consequences of cell-type-specific deletion of the CB1 receptor on the induction of hippocampal LTP and on CA1 pyramidal cell morphology. Deletion of CB1 receptor in GABAergic neurons in GABA-CB1-KO mice leads to a significantly decreased hippocampal LTP compared with WT controls. Concomitantly, CA1 pyramidal neurons have a significantly reduced dendritic branching both on the apical and on the basal dendrites. Moreover, the average spine density on the apical dendrites of CA1 pyramidal neurons is significantly diminished. In contrast, in mice lacking CB1 receptor in glutamatergic cells (Glu-CB1-KO), hippocampal LTP is significantly enhanced and CA1 pyramidal neurons show an increased branching and an increased spine density in the apical dendritic region. Together, these results indicate that the CB1 receptor signaling system both on inhibitory and excitatory neurons controls functional and structural synaptic plasticity of pyramidal neurons in the hippocampal CA1 region to maintain an appropriate homeostatic state upon neuronal activation. Consequently, if the CB1 receptor is lost in either neuronal population, an allostatic shift will occur leading to a long-term dysregulation of neuronal functions. Copyright © 2015 the authors 0270-6474/15/353842-09$15.00/0.

  9. The Effects of Excitatory and Inhibitory Social Cues on Cocaine-Seeking Behavior

    Directory of Open Access Journals (Sweden)

    Mark Andrew Smith

    2016-11-01

    Full Text Available Social partners influence the likelihood of using drugs, developing a substance use disorder, and relapse to drug use after a period of abstinence. Preclinical studies report that social cues influence the acquisition of cocaine use, the escalation of cocaine use over time, and the compulsive patterns of cocaine use that emerge during an extended binge. The purpose of this study was to examine the effects of social cues on the reinstatement of cocaine-seeking behavior after a period of abstinence. Male rats were obtained at weaning, assigned to triads (3 rats/cage, reared to adulthood, and implanted with intravenous catheters. Rats from each triad were then assigned to one of three conditions: (1 test rats were trained to self-administer cocaine and were tested for reinstatement, (2 cocaine partners were trained to self-administer cocaine and were predictive of response-contingent cocaine delivery, and (3 abstinent partners were not given access to cocaine and were predictive of extinction. Test rats alternated social partners every 5 days for 20 days such that responding was reinforced with cocaine in the presence of the cocaine partner (S+ for 10 days and not reinforced with cocaine in the presence of the abstinent partner (S- for 10 days. Responding of the test rats was then extinguished over 7 days under isolated conditions. Tests of reinstatement were then conducted in the presence of the cocaine partner and abstinent partner under extinction conditions. Neither social partner reinstated responding relative to that observed on the final day of extinction; however, responding was greater in the presence of the cocaine partner (S+ than the abstinent partner (S- during the reinstatement test. These data fail to demonstrate that a social partner reinstates cocaine-seeking behavior after a period of abstinence, but they do indicate that social partners can serve as either excitatory or inhibitory discriminative stimuli to influence drug

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

    National Research Council Canada - National Science Library

    Blakely, Pennelope K; Hussain, Shabbir; Carlin, Lindsey E; Irani, David N

    2015-01-01

    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...

  11. Human auditory evoked potentials. II - Effects of attention

    Science.gov (United States)

    Picton, T. W.; Hillyard, S. A.

    1974-01-01

    Attention directed toward auditory stimuli, in order to detect an occasional fainter 'signal' stimulus, caused a substantial increase in the N1 (83 msec) and P2 (161 msec) components of the auditory evoked potential without any change in preceding components. This evidence shows that human auditory attention is not mediated by a peripheral gating mechanism. The evoked response to the detected signal stimulus also contained a large P3 (450 msec) wave that was topographically distinct from the preceding components. This late positive wave could also be recorded in response to a detected omitted stimulus in a regular train and therefore seemed to index a stimulus-independent perceptual decision process.

  12. Peripheral electrical stimulation triggered by self-paced detection of motor intention enhances motor evoked potentials.

    Science.gov (United States)

    Niazi, Imran Khan; Mrachacz-Kersting, Natalie; Jiang, Ning; Dremstrup, Kim; Farina, Dario

    2012-07-01

    This paper proposes the development and experimental tests of a self-paced asynchronous brain-computer interfacing (BCI) system that detects movement related cortical potentials (MRCPs) produced during motor imagination of ankle dorsiflexion and triggers peripheral electrical stimulations timed with the occurrence of MRCPs to induce corticospinal plasticity. MRCPs were detected online from EEG signals in eight healthy subjects with a true positive rate (TPR) of 67.15 ± 7.87% and false positive rate (FPR) of 22.05 ±9.07%. The excitability of the cortical projection to the target muscle (tibialis anterior) was assessed before and after the intervention through motor evoked potentials (MEP) using transcranial magnetic stimulation (TMS). The peak of the evoked potential significantly (P=0.02) increased after the BCI intervention by 53 ± 43% (relative to preintervention measure), although the spinal excitability (tested by stretch reflexes) did not change. These results demonstrate for the first time that it is possible to alter the corticospinal projections to the tibialis anterior muscle by using an asynchronous BCI system based on online motor imagination that triggered peripheral stimulation. This type of repetitive proprioceptive feedback training based on self-generated brain signal decoding may be a requirement for purposeful skill acquisition in intact humans and in the rehabilitation of persons with brain damage.

  13. Effect of color of flash stimulus on variability of flash visual evoked potential latencies.

    Science.gov (United States)

    Subramanian, Senthil Kumar; Gaur, Giriwar Singh; Narayan, Sunil K

    2012-01-01

    Visual Evoked Potentials (VEPs) are evoked potentials generated in response to visual stimuli. The flash VEP (FVEP) is used less frequently than pattern-reversal VEP (PR-VEP) because; it shows great variations in both latency and amplitude in normal subjects. The advantage of FVEP is its feasibility in non-cooperative subjects, which circumvents the major limitation of PR-VEP. The present study was undertaken to assess the effect of change of color of flashlight on variability of FVEP latencies. Healthy subjects in the age group of 18-30 years underwent the standard stimulus using white light, followed by altered stimuli done with red and blue light. 2 trials were given for each eye, for each type of stimulus. The same set of studies was repeated at the same clock time the following day. The inter-individual and intra-individual variability in the peak latency of P2 and N2 waveforms was assessed using coefficient of variation (COV). Both inter-individual and intra-individual variability was less when monochromatic light was used. Between red and blue FVEP, inter-individual variability was less in blue FVEP and the results of intra-individual variability was inconclusive. Monochromatic stimulation preferably with blue light reduced both inter-individual and intra-individual variability seen in latency of P2 and N2 waveforms in FVEP and hence recommended in preference to standard white stimulus for FVEP recording.

  14. Changes in visual-evoked potential habituation induced by hyperventilation in migraine.

    Science.gov (United States)

    Coppola, Gianluca; Currà, Antonio; Sava, Simona Liliana; Alibardi, Alessia; Parisi, Vincenzo; Pierelli, Francesco; Schoenen, Jean

    2010-12-01

    Hyperventilation is often associated with stress, an established trigger factor for migraine. Between attacks, migraine is associated with a deficit in habituation to visual-evoked potentials (VEP) that worsens just before the attack. Hyperventilation slows electroencephalographic (EEG) activity and decreases the functional response in the occipital cortex during visual stimulation. The neural mechanisms underlying deficient-evoked potential habituation in migraineurs remain unclear. To find out whether hyperventilation alters VEP habituation, we recorded VEPs before and after experimentally induced hyperventilation lasting 3 min in 18 healthy subjects and 18 migraine patients between attacks. We measured VEP P100 amplitudes in six sequential blocks of 100 sweeps and habituation as the change in amplitude over the six blocks. In healthy subjects, hyperventilation decreased VEP amplitude in block 1 and abolished the normal VEP habituation. In migraine patients, hyperventilation further decreased the already low block 1 amplitude and worsened the interictal habituation deficit. Hyperventilation worsens the habituation deficit in migraineurs possibly by increasing dysrhythmia in the brainstem-thalamo-cortical network.

  15. Visual evoked potentials in diagnostics of optic neuropathy associated with renal failure

    Directory of Open Access Journals (Sweden)

    Małgorzata Jurys

    2017-01-01

    Full Text Available Chronic renal failure is associated with many neurological complications. Due to accumulation of uremic neurotoxins axonal degeneration with its secondary demyelination occurs, which results in development of polineuropathy in 60-100% of patients with chronic renal failure. One of the most severe peripheral neuropathy is optic neuropathy. It is associated with visual deterioration and reduction in quality of life. Symptoms of the optic neuropathy may appear either before or after dialysis therapy. They often worsen after renal transplant, probably due to immunosuppressive regimen. Early diagnostics of the optic neuropathy became possible by using visual evoked potentials (VEP. This reliable, sensitive and noninvasive technique provides a direct measure of subclinical impairment of visual pathways. Among hemodialysed or immunosupressed patients one can observe abnormal VEP parameters – especially prolonged latency of the P100 component, less often fluctuation of its amplitude. These alterations are pronounced even if clinical examination reveals no abnormalities. This review presents a summary of current use of visual evoked potentials in monitoring of patients with chronic renal failure.

  16. Contact heat evoked potentials using simultaneous EEG and fMRI and their correlation with evoked pain

    Directory of Open Access Journals (Sweden)

    Atherton Duncan

    2008-12-01

    Full Text Available Abstract Background The Contact Heat Evoked Potential Stimulator (CHEPS utilises rapidly delivered heat pulses with adjustable peak temperatures to stimulate the differential warm/heat thresholds of receptors expressed by Aδ and C fibres. The resulting evoked potentials can be recorded and measured, providing a useful clinical tool for the study of thermal and nociceptive pathways. Concurrent recording of contact heat evoked potentials using electroencephalogram (EEG and functional magnetic resonance imaging (fMRI has not previously been reported with CHEPS. Developing simultaneous EEG and fMRI with CHEPS is highly desirable, as it provides an opportunity to exploit the high temporal resolution of EEG and the high spatial resolution of fMRI to study the reaction of the human brain to thermal and nociceptive stimuli. Methods In this study we have recorded evoked potentials stimulated by 51°C contact heat pulses from CHEPS using EEG, under normal conditions (baseline, and during continuous and simultaneous acquisition of fMRI images in ten healthy volunteers, during two sessions. The pain evoked by CHEPS was recorded on a Visual Analogue Scale (VAS. Results Analysis of EEG data revealed that the latencies and amplitudes of evoked potentials recorded during continuous fMRI did not differ significantly from baseline recordings. fMRI results were consistent with previous thermal pain studies, and showed Blood Oxygen Level Dependent (BOLD changes in the insula, post-central gyrus, supplementary motor area (SMA, middle cingulate cortex and pre-central gyrus. There was a significant positive correlation between the evoked potential amplitude (EEG and the psychophysical perception of pain on the VAS. Conclusion The results of this study demonstrate the feasibility of recording contact heat evoked potentials with EEG during continuous and simultaneous fMRI. The combined use of the two methods can lead to identification of distinct patterns of brain

  17. Glutamatergic modulation of separation distress: profound emotional effects of excitatory amino acids in chicks.

    Science.gov (United States)

    Normansell, Larry; Panksepp, Jaak

    2011-10-01

    Pre-clinical models of brain affective circuits provide relevant evidence for understanding the brain systems that figure heavily in psychiatric disorders. Social isolation and the resulting separation distress contribute to the onset of depression. In this work, the effects of excitatory amino acids (EAA) on isolation-induced distress vocalization (DV) were assessed in young domestic chicks. Both glutamate and quisqualate (QA) produced dose-dependent reductions in DVs, while N-methyl-d-aspartate (NMDA) and kainate (KA) increased DVs. Such a differential pattern of responsiveness may indicate the presence of reciprocal or interacting EAA systems in the brain control of separation distress. Administration of either the NMDA receptor antagonist 2-amino-5-phosphonovalerate (APV) or the broad-spectrum antagonist gamma-d-glutamylglycine (DGG) greatly reduced DVs, as did the antagonist 2-amino-4-phosphonobutyrate (APB). APV did not attenuate the increase in vocalizations seen after NMDA or KA administration. DGG, however, was able to block the increase in calling produced by either of these agonists, suggesting a KA receptor mechanism. KA treatment inhibited the ability of other chicks, or auditory and somatosensory information, to suppress DVs. KA-treated animals exhibited a hyperemotional behavior pattern during which a variety of motivated behaviors were disrupted including reactions to novel objects, approaching the flock, and foraging. They could not sustain a coherent flock-like social cohesion, but exhibited strong fixed-action patterns of flight interspersed with hiding and crouching behaviors. The evident behavioral changes suggest that glutamatergic synapses directly influence sensory, motor and emotional processes in the brain and may be especially important in the integration of environmental stimuli with emotional central state processes of animals. Considering that unresolved social loss and grief have been deemed to be among the main precipitating causes

  18. Brainstem auditory evoked responses in man. 1: Effect of stimulus rise-fall time and duration

    Science.gov (United States)

    Hecox, K.; Squires, N.; Galambos, R.

    1975-01-01

    Short latency (under 10 msec) responses elicited by bursts of white noise were recorded from the scalps of human subjects. Response alterations produced by changes in the noise burst duration (on-time), inter-burst interval (off-time), and onset and offset shapes were analyzed. The latency of the most prominent response component, wave V, was markedly delayed with increases in stimulus rise time but was unaffected by changes in fall time. Increases in stimulus duration, and therefore in loudness, resulted in a systematic increase in latency. This was probably due to response recovery processes, since the effect was eliminated with increases in stimulus off-time. The amplitude of wave V was insensitive to changes in signal rise and fall times, while increasing signal on-time produced smaller amplitude responses only for sufficiently short off-times. It was concluded that wave V of the human auditory brainstem evoked response is solely an onset response.

  19. 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

  20. Pattern visual evoked responses in hereditary spastic paraplegia

    Science.gov (United States)

    Livingstone, I R; Mastaglia, F L; Edis, R; Howe, J W

    1981-01-01

    Pattern visual evoked responses were studied in 13 patients from nine families with dominant herditary spastic paraplegia and in seven sporadic cases. The responses were normal in all the dominantly inherited cases but abnormal in three of the seven sporadic cases. PMID:7217977

  1. 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 ...

  2. Temporal Tuning Effects in the Visually Evoked Response,

    Science.gov (United States)

    1985-08-01

    Berger (1932) also observed that these brain waves are slowed in states of depressed function such as sleep activity and that they can be blocked by...Ma4cay and Jefferys, 1973). Transient VER’s, polyphasic in form and 200-500 milliseconds in duration, are evoked by stepwise changes in one or more per

  3. Visual evoked potentials in workers with chronic solvent encephalopathy

    NARCIS (Netherlands)

    Verberk, Maarten M.; Brons, Joke T.; Sallé, Herman J. A.

    2004-01-01

    Objectives. Two promising variations of visual evoked potentials (VEPs) were studied in solvent-exposed workers: the effect of a low-contrast stimulus in comparison with the usually applied high contrast, and the ability of pattern-onset VEP to reveal damage to specific visual cortical areas. In

  4. The computation of evoked heart rate and blood pressure

    NARCIS (Netherlands)

    Koers, G.; Mulder, L.J.M.; van der Veen, F.M.

    1999-01-01

    For many years psychophysiologists have been interested in stimulus related changes in heart rate and blood pressure. To represent these evoked heart rate and blood pressure patterns, heart rate and blood pressure data have to be transformed into equidistant time series. This paper presents an

  5. The masseteric reflex evoked by tooth and denture tapping.

    Science.gov (United States)

    Brodin, P; Fløystrand, F; Orstavik, J

    1991-07-01

    The characteristics of the masseter reflex evoked by tapping a maxillary incisor were compared with the reflex pattern evoked by tapping a corresponding denture tooth after insertion of an immediate denture. Up to three inhibitory phases (I-1, I-2 and I-3), followed by excitation, were found on an averaged EMG. The tapping force threshold for the early inhibitory phase was lower than for the late phases. The pattern of the reflex was generally the same before and after insertion of the denture, but the threshold values increased. After insertion of the denture, the threshold for I-1 increased from 1 +/- 0.3N to 2.2 +/- 0.4N, the threshold for I-2 increased from 2.4 +/- 0.8N to 3.8 +/- 0.9N, and the threshold for I-3 increased from 5.1 +/- 0.6N to 8.3 +/- 0.9N. The latency period for I-1 also increased from 12.3 +/- 0.5 ms to 13.1 +/- 0.3 ms after insertion of the denture. After relining, the threshold for evoking I-1 decreased from 2.7 +/- 1.2N to 1.2 +/- 0.6N. It was assumed that the mechanoreceptors situated in the mucosa under the denture base could take over the functional role of the periodontal mechanoreceptors for evoking the masseter reflex during tapping, and that these afferents probably had connections to the same interneurones.

  6. Comparison of clinical and evoked pain measures in fibromyalgia.

    Science.gov (United States)

    Harris, Richard E; Gracely, Richard H; McLean, Samuel A; Williams, David A; Giesecke, Thorsten; Petzke, Frank; Sen, Ananda; Clauw, Daniel J

    2006-07-01

    Evoked pain measures such as tender point count and dolorimetry are often used to determine tenderness in studies of fibromyalgia (FM). However, these measures frequently do not improve in clinical trials and are known to be influenced by factors other than pain such as distress and expectancy. The purpose of this investigation was to determine whether evoked pain paradigms that present pressure stimuli in a random fashion (eg, Multiple Random Staircase [MRS]) would track with clinical pain improvement in patients with FM better than traditional measures. Sixty-five subjects enrolled in a randomized clinical trial of acupuncture were observed longitudinally. Clinical pain was measured on a 101-point numerical rating scale (NRS) and the Short Form McGill Pain Questionnaire (SF-MPQ), whereas evoked pressure sensitivity was assessed via manual tender point count, dolorimetry, and MRS methods. Improvements in clinical pain and evoked pain were assessed irrespective of group assignment. Improvement was seen in clinical pain during the course of the trial as measured by both NRS (P = .032) and SF-MPQ (P = .001). The MRS was the only evoked pain measure to improve correspondingly with treatment (MRS, P = .001; tender point count and dolorimeter, P > .05). MRS change scores were correlated with changes in NRS pain ratings (P = .003); however, this association was not stronger than tender point or dolorimetry correlations with clinical pain improvement (P > .05). Pain sensitivity as assessed by random paradigms was associated with improvements in clinical FM pain. Sophisticated pain testing paradigms might be responsive to change in clinical trials. Trials in fibromyalgia often use both clinical and experimental methods of pain assessment; however, these two outcomes are often poorly correlated. We explore the relationship between changes in clinical and experimental pain within FM patients. Pressure pain testing that applies stimuli in a random order is associated with

  7. 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.

  8. Multiple excitatory and inhibitory neural signals converge to fine-tune Caenorhabditis elegans feeding to food availability

    Science.gov (United States)

    Dallière, Nicolas; Bhatla, Nikhil; Luedtke, Zara; Ma, Dengke K.; Woolman, Jonathan; Walker, Robert J.; Holden-Dye, Lindy; O’Connor, Vincent

    2016-01-01

    How an animal matches feeding to food availability is a key question for energy homeostasis. We addressed this in the nematode Caenorhabditis elegans, which couples feeding to the presence of its food (bacteria) by regulating pharyngeal activity (pumping). We scored pumping in the presence of food and over an extended time course of food deprivation in wild-type and mutant worms to determine the neural substrates of adaptive behavior. Removal of food initially suppressed pumping but after 2 h this was accompanied by intermittent periods of high activity. We show pumping is fine-tuned by context-specific neural mechanisms and highlight a key role for inhibitory glutamatergic and excitatory cholinergic/peptidergic drives in the absence of food. Additionally, the synaptic protein UNC-31 [calcium-activated protein for secretion (CAPS)] acts through an inhibitory pathway not explained by previously identified contributions of UNC-31/CAPS to neuropeptide or glutamate transmission. Pumping was unaffected by laser ablation of connectivity between the pharyngeal and central nervous system indicating signals are either humoral or intrinsic to the enteric system. This framework in which control is mediated through finely tuned excitatory and inhibitory drives resonates with mammalian hypothalamic control of feeding and suggests that fundamental regulation of this basic animal behavior may be conserved through evolution from nematode to human.—Dallière, N., Bhatla, N., Luedtke, Z., Ma, D. K., Woolman, J., Walker, R. J., Holden-Dye, L., O’Connor, V. Multiple excitatory and inhibitory neural signals converge to fine-tune Caenorhabditis elegans feeding to food availability. PMID:26514165

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Bioavailability Studies and in vitro Profiling of the Selective Excitatory Amino Acid Transporter Subtype 1 (EAAT1) Inhibitor UCPH‐102

    DEFF Research Database (Denmark)

    Haym, Isabell; Huynh, Tri H. V.; Hansen, Stinne W.

    2016-01-01

    Although the selective excitatory amino acid transporter subtype 1 (EAAT1) inhibitor UCPH‐101 has become a standard pharmacological tool compound for in vitro and ex vivo studies in the EAAT research field, its inability to penetrate the blood–brain barrier makes it unsuitable for in vivo studies...... displayed substantially improved properties in this respect. In vitro profiling of UCPH‐102 (10 μm) at 51 central nervous system targets in radioligand binding assays strongly suggests that the compound is completely selective for EAAT1. Finally, in a rodent locomotor model, p.o. administration of UCPH‐102...

  11. 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, the af...... that the afferent nerve provides powerful and reliable excitatory input as well as a feed-forward inhibitory input, which is partially presynaptic in origin. These results question the cellular location within the DON where cancelation of expected incoming signals occurs....

  12. 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...

  13. Origin of facilitation of motor-evoked potentials after paired magnetic stimulation: direct recording of epidural activity in conscious humans.

    Science.gov (United States)

    Di Lazzaro, V; Pilato, F; Oliviero, A; Dileone, M; Saturno, E; Mazzone, P; Insola, A; Profice, P; Ranieri, F; Capone, F; Tonali, P A; Rothwell, J C

    2006-10-01

    A magnetic transcranial conditioning stimulus given over the motor cortex at intensities below active threshold for obtaining motor-evoked potentials (MEPs) facilitates EMG responses evoked at rest in hand muscles by a suprathreshold magnetic stimulus given 10-25 ms later. This is known as intracortical facilitation (ICF). We recorded descending volleys produced by single and paired magnetic motor cortex stimulation through high cervical epidural electrodes implanted for pain relief in six conscious patients. At interstimulus intervals (ISIs) of 10 and 15 ms, although MEP was facilitated, there was no change in the amplitude or number of descending volleys. An additional I wave sometimes was observed at 25 ms ISI. In one subject, we also evaluated the effects of reversing the direction of the induced current in the brain. At 10 ms ISI, the facilitation of the MEPs disappeared and was replaced by slight suppression; at 2 ms ISI, there was a pronounced facilitation of epidural volleys. Subsequent experiments on healthy subjects showed that a conditioning stimulus capable of producing ICF of MEPs had no effect on the EMG response evoked by transmastoidal electrical stimulation of corticospinal tract. We conclude that ICF occurs because either 1) the conditioning stimulus has a (thus far undetected) effect on spinal cord excitability that increases its response to the same amplitude test volley or 2) that it can alter the composition (but not the amplitude) of the descending volleys set up by the test stimulus such that a larger proportion of the activity is destined for the target muscle.

  14. Clinical evaluation of cochlear hearing status in dogs using evoked otoacoustic emissions.

    Science.gov (United States)

    Gonçalves, R; McBrearty, A; Pratola, L; Calvo, G; Anderson, T J; Penderis, J

    2012-06-01

    Evoked otoacoustic emission testing is the preferred test in human patients for sensorineural deafness screening in neonates and cochlear outer hair cell function monitoring in adults. This study evaluated evoked otoacoustic emission testing for cochlear function assessment in dogs within a clinical setting. Two populations of anaesthetised dogs were included. In group 1 the evoked otoacoustic emission response was compared to the brainstem auditory evoked response in 10 dogs having hearing assessment. Group 2 comprised 43 presumed normal dogs, in which the suitability of two types of evoked otoacoustic emissions, transient-evoked and distortion product otoacoustic emissions, were evaluated (brainstem auditory evoked response was not performed in this group). Valid transient-evoked otoacoustic emission and distortion-product otoacoustic emission responses were successfully recorded within the clinical setting and correctly identified deaf and hearing ears. Within presumed healthy dogs, normal otoacoustic emission response was demonstrated in more than 80% of dogs using a single, short distortion-product otoacoustic emission run and in 78% of dogs with valid transient-evoked otoacoustic emission responses using a series of three repeated transient-evoked otoacoustic emission short runs. Transient-evoked otoacoustic emission and distortion-product otoacoustic emission testing provided a rapid, non-invasive frequency-specific assessment of cochlear function. Transient-evoked otoacoustic emission and distortion product otoacoustic emission testing is suitable as a screening procedure to detect loss of cochlear function in dogs, although further investigation is needed. © 2012 British Small Animal Veterinary Association.

  15. 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

  16. The proportion of common synaptic input to motor neurons increases with an increase in net excitatory input.

    Science.gov (United States)

    Castronovo, Anna Margherita; Negro, Francesco; Conforto, Silvia; Farina, Dario

    2015-12-01

    α-Motor neurons receive synaptic inputs from spinal and supraspinal centers that comprise components either common to the motor neuron pool or independent. The input shared by motor neurons--common input--determines force control. The aim of the study was to investigate the changes in the strength of common synaptic input delivered to motor neurons with changes in force and with fatigue, two conditions that underlie an increase in the net excitatory drive to the motor neurons. High-density surface electromyogram (EMG) signals were recorded from the tibialis anterior muscle during contractions at 20, 50, and 75% of the maximal voluntary contraction force (in 3 sessions separated by at least 2 days), all sustained until task failure. EMG signal decomposition identified the activity of a total of 1,245 motor units. The coherence values between cumulative motor unit spike trains increased with increasing force, especially for low frequencies. This increase in coherence was not observed when comparing two subsets of motor units having different recruitment thresholds, but detected at the same force level. Moreover, the coherence values for frequencies input to motor neurons increases with respect to independent input when the net excitatory drive to motor neurons increases as a consequence of a change in force and fatigue. Copyright © 2015 the American Physiological Society.

  17. Up-Regulation of the Excitatory Amino Acid Transporters EAAT1 and EAAT2 by Mammalian Target of Rapamycin

    Directory of Open Access Journals (Sweden)

    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.

  18. Medial superior olivary neurons receive surprisingly few excitatory and inhibitory inputs with balanced strength and short-term dynamics.

    Science.gov (United States)

    Couchman, Kiri; Grothe, Benedikt; Felmy, Felix

    2010-12-15

    Neurons in the medial superior olive (MSO) process microsecond interaural time differences, the major cue for localizing low-frequency sounds, by comparing the relative arrival time of binaural, glutamatergic excitatory inputs. This coincidence detection mechanism is additionally shaped by highly specialized glycinergic inhibition. Traditionally, it is assumed that the binaural inputs are conveyed by many independent fibers, but such an anatomical arrangement may decrease temporal precision. Short-term depression on the other hand might enhance temporal fidelity during ongoing activity. For the first time we show that binaural coincidence detection in MSO neurons may require surprisingly few but strong inputs, challenging long-held assumptions about mammalian coincidence detection. This study exclusively uses adult gerbils for in vitro electrophysiology, single-cell electroporation and immunohistochemistry to characterize the size and short-term plasticity of inputs to the MSO. We find that the excitatory and inhibitory inputs to the MSO are well balanced both in strength and short-term dynamics, redefining this fastest of all mammalian coincidence detector circuits.

  19. Fear learning increases the number of polyribosomes associated with excitatory and inhibitory synapses in the barrel cortex.

    Directory of Open Access Journals (Sweden)

    Malgorzata Jasinska

    Full Text Available Associative fear learning, resulting from whisker stimulation paired with application of a mild electric shock to the tail in a classical conditioning paradigm, changes the motor behavior of mice and modifies the cortical functional representation of sensory receptors involved in the conditioning. It also induces the formation of new inhibitory synapses on double-synapse spines of the cognate barrel hollows. We studied density and distribution of polyribosomes, the putative structural markers of enhanced synaptic activation, following conditioning. By analyzing serial sections of the barrel cortex by electron microscopy and stereology, we found that the density of polyribosomes was significantly increased in dendrites of the barrel activated during conditioning. The results revealed fear learning-induced increase in the density of polyribosomes associated with both excitatory and inhibitory synapses located on dendritic spines (in both single- and double-synapse spines and only with the inhibitory synapses located on dendritic shafts. This effect was accompanied by a significant increase in the postsynaptic density area of the excitatory synapses on single-synapse spines and of the inhibitory synapses on double-synapse spines containing polyribosomes. The present results show that associative fear learning not only induces inhibitory synaptogenesis, as demonstrated in the previous studies, but also stimulates local protein synthesis and produces modifications of the synapses that indicate their potentiation.

  20. Multiple excitatory and inhibitory neural signals converge to fine-tune Caenorhabditis elegans feeding to food availability.

    Science.gov (United States)

    Dallière, Nicolas; Bhatla, Nikhil; Luedtke, Zara; Ma, Dengke K; Woolman, Jonathan; Walker, Robert J; Holden-Dye, Lindy; O'Connor, Vincent

    2016-02-01

    How an animal matches feeding to food availability is a key question for energy homeostasis. We addressed this in the nematode Caenorhabditis elegans, which couples feeding to the presence of its food (bacteria) by regulating pharyngeal activity (pumping). We scored pumping in the presence of food and over an extended time course of food deprivation in wild-type and mutant worms to determine the neural substrates of adaptive behavior. Removal of food initially suppressed pumping but after 2 h this was accompanied by intermittent periods of high activity. We show pumping is fine-tuned by context-specific neural mechanisms and highlight a key role for inhibitory glutamatergic and excitatory cholinergic/peptidergic drives in the absence of food. Additionally, the synaptic protein UNC-31 [calcium-activated protein for secretion (CAPS)] acts through an inhibitory pathway not explained by previously identified contributions of UNC-31/CAPS to neuropeptide or glutamate transmission. Pumping was unaffected by laser ablation of connectivity between the pharyngeal and central nervous system indicating signals are either humoral or intrinsic to the enteric system. This framework in which control is mediated through finely tuned excitatory and inhibitory drives resonates with mammalian hypothalamic control of feeding and suggests that fundamental regulation of this basic animal behavior may be conserved through evolution from nematode to human. © FASEB.

  1. High-Throughput Genetic Screen for Synaptogenic Factors: Identification of LRP6 as Critical for Excitatory Synapse Development

    Directory of Open Access Journals (Sweden)

    Kamal Sharma

    2013-12-01

    Full Text Available Genetic screens in invertebrates have discovered many synaptogenic genes and pathways. However, similar genetic studies have not been possible in mammals. We have optimized an automated high-throughput platform that employs automated liquid handling and imaging of primary mammalian neurons. Using this platform, we have screened 3,200 shRNAs targeting 800 proteins. One of the hits identified was LRP6, a coreceptor for canonical Wnt ligands. LRP6 regulates excitatory synaptogenesis and is selectively localized to excitatory synapses. In vivo knockdown of LRP6 leads to a reduction in the number of functional synapses. Moreover, we show that the canonical Wnt ligand, Wnt8A, promotes synaptogenesis via LRP6. These results provide a proof of principle for using a high-content approach to screen for synaptogenic factors in the mammalian nervous system and identify and characterize a Wnt ligand receptor complex that is critical for the development of functional synapses in vivo.

  2. Examining the limits of cellular adaptation bursting mechanisms in biologically-based excitatory networks of the hippocampus.

    Science.gov (United States)

    Ferguson, K A; Njap, F; Nicola, W; Skinner, F K; Campbell, S A

    2015-12-01

    Determining the biological details and mechanisms that are essential for the generation of population rhythms in the mammalian brain is a challenging problem. This problem cannot be addressed either by experimental or computational studies in isolation. Here we show that computational models that are carefully linked with experiment provide insight into this problem. Using the experimental context of a whole hippocampus preparation in vitro that spontaneously expresses theta frequency (3-12 Hz) population bursts in the CA1 region, we create excitatory network models to examine whether cellular adaptation bursting mechanisms could critically contribute to the generation of this rhythm. We use biologically-based cellular models of CA1 pyramidal cells and network sizes and connectivities that correspond to the experimental context. By expanding our mean field analyses to networks with heterogeneity and non all-to-all coupling, we allow closer correspondence with experiment, and use these analyses to greatly extend the range of parameter values that are explored. We find that our model excitatory networks can produce theta frequency population bursts in a robust fashion.Thus, even though our networks are limited by not including inhibition at present, our results indicate that cellular adaptation in pyramidal cells could be an important aspect for the occurrence of theta frequency population bursting in the hippocampus. These models serve as a starting framework for the inclusion of inhibitory cells and for the consideration of additional experimental features not captured in our present network models.

  3. Neonatal maternal separation delays the GABA excitatory-to-inhibitory functional switch by inhibiting KCC2 expression.

    Science.gov (United States)

    Furukawa, Minami; Tsukahara, Takao; Tomita, Kazuo; Iwai, Haruki; Sonomura, Takahiro; Miyawaki, Shouichi; Sato, Tomoaki

    2017-11-25

    The excitatory-to-inhibitory functional switch of γ-aminobutyric acid (GABA; GABA switch), which normally occurs in the first to the second postnatal week in the hippocampus, is necessary for the development of appropriate central nervous system function. A deficit in GABAergic inhibitory function could cause excitatory/inhibitory (E/I) neuron imbalance that is found in many neurodegenerative disorders. In the present study, we examined whether neonatal stress can affect the timing of the GABA functional switch and cause disorders during adolescence. Neonatal stress was induced in C57BL/6J male mouse pups by maternal separation (MS) on postnatal days (PND) 1-21. Histological quantification of K+-Cl- co-transporter (KCC2) and Ca2+ imaging were performed to examine the timing of the GABA switch during the MS period. To evaluate the influence of neonatal MS on adolescent hippocampal function, we quantified KCC2 expression and evaluated hippocampal-related behavioral tasks at PND35-38. We showed that MS delayed the timing of the GABA switch in the hippocampus and inhibited the increase in membrane KCC2 expression, with KCC2 expression inhibition persisting until adolescence. Behavioral tests showed impaired cognition, declined attention, hyperlocomotion, and aggressive character in maternally separated mice. Taken together, our results show that neonatal stress delayed the timing of the GABA switch, which could change the E/I balance and cause neurodegenerative disorders in later life. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. 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

  5. [Motor evoked potentials of the perineal floor. Preliminary results].

    Science.gov (United States)

    Opsomer, R J; Van Cangh, P J; Humblet, Y; Abi Aad, A; Rossini, P M

    1989-01-01

    Neuromotor pathways from the brain to the pelvic floor have been poorly documented. The recent development of Motor Evoked Potentials may well fill this gap in our basic knowledge. Our technique consists of transcutaneous stimulation of the motor cortex and sacral roots with a magnetic device while recording the evoked response from the bulbocavernosus muscle and anal sphincter. Cortical stimulation is performed first at rest and then during voluntary contraction of the examined muscles ("facilitation" procedure). Sacral root stimulation is performed at rest. Stimulation at 2 different levels allows measurement of the total transit time (brain to muscle transit time) and the peripheral transit time (sacral roots to muscle). By subtracting the latter from the former, the central transit time (brain to sacral roots) is obtained. The technique is painless, and to our knowledge no side effects have been reported. The authors present the preliminary results of this new technique.

  6. Evoked potentials and head injury. 2. Clinical applications.

    Science.gov (United States)

    Rappaport, M; Hopkins, H K; Hall, K; Belleza, T

    1981-10-01

    The method of rating abnormality of evoked brain potential patterns and assessing the extent and severity of cortical and subcortical brain dysfunction in head injury patients described in Part I is applied in a clinical context. Evoked potential abnormality (EPA) scores are found to be significantly correlated both with admission and outcome disability approximately one year after head injury. Correlations increase with the increase in the number of sensory modalities tested. Correlations between EPA scores and clinical disability (measured by the Disability Rating Scale) decrease with time after injury. Significant correlations, however, persist for about 60 days after onset of injury. It was found that EP pattern abnormalities can reflect specific sensory (and at times motor) deficits in noncommunicative patients and thereby contribute significantly to early treatment and rehabilitation planning.

  7. Binocular interactions in the guinea pig's visual-evoked potentials.

    Science.gov (United States)

    Ates, Kahraman; Demirtas, Serdar; Goksoy, Cuneyt

    2006-12-13

    In this study, binocular interaction in guinea pigs is evaluated using bioelectrical activities. A difference potential, as evidence of an interaction, is calculated by subtracting the sum of visual-evoked potentials recorded by left and right monocular visual stimulations from the potential recorded by binocular stimulation. A negative monophasic wave with an average amplitude of 15.1 microV and an average latency of 106 ms is observed in the difference potential. This finding implies that the P100 is the main guinea pig visual-evoked potential wave that is affected by binocular interaction. Binocular interaction is also observed in the waves N75 and N140, although with a smaller amplitude. No interaction is observed in the segments of P55 and P200 waves.

  8. Multimodality evoked potentials in occupational exposure to metallic mercury vapour.

    Science.gov (United States)

    Langauer-Lewowicka, H; Kazibutowska, Z

    1989-01-01

    Central nervous system dysfunction among workers exposed to metallic mercury was studied by measuring somatosensory evoked potentials (SSEPs) and visual evoked potentials (VEPs). The examinations were conducted in 28 workers suspected of chronic mercury intoxication. They were exposed to Hg for a period ranging from 4-34 years (mean 22.1) in an acetic aldehyde and chlorine manufacturing plant. The increase of amplitude of N20 SSEP (13 cases) and elongation of its latency were frequent abnormalities in the examined group. The latency of N20 was significantly longer in the exposed group in comparison with the control one, the amplitude of N20 was also significantly higher. Significantly prolonged latency of P100 VEP was found in the group exposed to Hg. These findings suggest the possibility of an adverse effect due to Hg on the central part of the somatosensory and visual pathway.

  9. 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.

  10. Evoked response audiometry used in testing auditory organs of miners

    Energy Technology Data Exchange (ETDEWEB)

    Malinowski, T.; Klepacki, J.; Wagstyl, R.

    1980-01-01

    The evoked response audiometry method of testing hearing loss is presented and the results of comparative studies using subjective tonal audiometry and evoked response audiometry in tests of 56 healthy men with good hearing are discussed. The men were divided into three groups according to age and place of work: work place without increased noise; work place with noise and vibrations (at drilling machines); work place with noise and shocks (work at excavators in surface coal mines). The ERA-MKII audiometer produced by the Medelec-Amplaid firm was used. Audiometric threshhold curves for the three groups of tested men are given. At frequencies of 500, 1000 and 4000 Hz mean objective auditory threshhold was shifted by 4-9.5 dB in comparison to the subjective auditory threshold. (21 refs.) (In Polish)

  11. 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...

  12. The Dynamic Functional Capacity Theory: Music Evoked Emotions

    OpenAIRE

    Klineburger, Philip C

    2014-01-01

    The music-evoked emotion literature implicates many brain regions involved in emotional processing but is currently lacking a model that specifically explains how they temporally and dynamically interact to produce intensely pleasurable emotions. A conceptual model, The Dynamic Functional Capacity Theory (DFCT), is proposed that provides a foundation for the further understanding of how brain regions interact to produce intense intensely pleasurable emotions. The DFCT claims th...

  13. Multimodality evoked potentials in HTLV-I associated myelopathy.

    OpenAIRE

    Kakigi, R; Shibasaki, H; Kuroda, Y; Endo, C; Oda, K; Ikeda, A; Hashimoto, K

    1988-01-01

    Multimodality evoked potentials (EPs) consisting of somatosensory EPs (SEPs), visual EPs (VEPs) and brainstem auditory EPs (BAEPs) were studied in 16 cases with HTLV-I associated myelopathy (HAM). Median nerve SEPs were normal in all cases. In posterior tibial nerve SEPs, the potential recorded at the 12th thoracic spinal process was normal in every case but cortical components were significantly prolonged in 10 cases, although five of these showed no sensory impairment. BAEPs were normal in ...

  14. Establishing an evoked-potential vision-tracking system

    Science.gov (United States)

    Skidmore, Trent A.

    1991-01-01

    This paper presents experimental evidence to support the feasibility of an evoked-potential vision-tracking system. The topics discussed are stimulator construction, verification of the photic driving response in the electroencephalogram, a method for performing frequency separation, and a transient-analysis example. The final issue considered is that of object multiplicity (concurrent visual stimuli with different flashing rates). The paper concludes by discussing several applications currently under investigation.

  15. 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.

  16. 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.

  17. Brainstem auditory evoked potentials in children with lead exposure

    Directory of Open Access Journals (Sweden)

    Katia de Freitas Alvarenga

    2015-02-01

    Full Text Available Introduction: Earlier studies have demonstrated an auditory effect of lead exposure in children, but information on the effects of low chronic exposures needs to be further elucidated. Objective: To investigate the effect of low chronic exposures of the auditory system in children with a history of low blood lead levels, using an auditory electrophysiological test. Methods: Contemporary cross-sectional cohort. Study participants underwent tympanometry, pure tone and speech audiometry, transient evoked otoacoustic emissions, and brainstem auditory evoked potentials, with blood lead monitoring over a period of 35.5 months. The study included 130 children, with ages ranging from 18 months to 14 years, 5 months (mean age 6 years, 8 months ± 3 years, 2 months. Results: The mean time-integrated cumulative blood lead index was 12 µg/dL (SD ± 5.7, range:2.433. All participants had hearing thresholds equal to or below 20 dBHL and normal amplitudes of transient evoked otoacoustic emissions. No association was found between the absolute latencies of waves I, III, and V, the interpeak latencies I-III, III-V, and I-V, and the cumulative lead values. Conclusion: No evidence of toxic effects from chronic low lead exposures was observed on the auditory function of children living in a lead contaminated area.

  18. Brainstem auditory evoked potentials in children with lead exposure.

    Science.gov (United States)

    Alvarenga, Katia de Freitas; Morata, Thais Catalani; Lopes, Andrea Cintra; Feniman, Mariza Ribeiro; Corteletti, Lilian Cassia Bornia Jacob

    2015-01-01

    Earlier studies have demonstrated an auditory effect of lead exposure in children, but information on the effects of low chronic exposures needs to be further elucidated. To investigate the effect of low chronic exposures of the auditory system in children with a history of low blood lead levels, using an auditory electrophysiological test. Contemporary cross-sectional cohort. Study participants underwent tympanometry, pure tone and speech audiometry, transient evoked otoacoustic emissions, and brainstem auditory evoked potentials, with blood lead monitoring over a period of 35.5 months. The study included 130 children, with ages ranging from 18 months to 14 years, 5 months (mean age 6 years, 8 months ± 3 years, 2 months). The mean time-integrated cumulative blood lead index was 12 μg/dL (SD ± 5.7, range: 2.433). All participants had hearing thresholds equal to or below 20 dBHL and normal amplitudes of transient evoked otoacoustic emissions. No association was found between the absolute latencies of waves I, III, and V, the interpeak latencies I-III, III-V, and I-V, and the cumulative lead values. No evidence of toxic effects from chronic low lead exposures was observed on the auditory function of children living in a lead contaminated area. Copyright © 2014 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  19. 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.

  20. The hypothalamic peptides, beta-endorphin, neuropeptide K and interleukin-1 beta, and the opiate morphine, enhance the excitatory amino acid-induced LH release under the influence of gonadal steroids.

    Science.gov (United States)

    Bonavera, J J; Sahu, A; Kalra, S P; Kalra, P S

    1994-10-01

    Several hypothalamic neuropeptides and amino acids are known to inhibit or excite pituitary luteinizing hormone (LH) release, but the precise interplay between these 2 classes of signals in episodic LH discharge is not known. In this study, we have evaluated the interaction between neuropeptides shown previously to inhibit LH release in castrated rats and the excitatory amino acid agonist, N-methyl-D-aspartate (NMDA), on LH release in intact male rats. Rats received a permanent intracerebroventricular (i.c.v.) cannula and 9-12 days later an intrajugular cannula for frequent blood sampling. The next day, rats received i.c.v. either saline (SAL, 3 microliters, controls) or a neuropeptide: the opioid beta-endorphin (beta-END; 2.9 nmol), the tachykinin neuropeptide K (NPK, 2.5 nmol) or the cytokine interleukin-1 beta (IL-1 beta, 5.9 pmol) in SAL. The LH response to 2 consecutive i.v. injections of NMDA (5 mg/kg) at 30 min intervals was evaluated. In control rats, each NMDA injection evoked a significant release of LH at 10 min. Quite unexpectedly, the three peptides, instead of exerting an inhibitory effect, enhanced the LH response to NMDA. The peak plasma LH levels after each NMDA injection and the cumulative LH responses were significantly higher in peptide-treated than in control rats. This peculiar ability of the peptides that inhibit LH release in castrated rats, to potentiate the NMDA-induced LH release in the presence of gonadal steroids was further validated in female rats treated with an opiate receptor agonist, morphine (MOR) which is also known to suppress LH release in ovariectomized rats.(ABSTRACT TRUNCATED AT 250 WORDS)

  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. 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

  3. Deletion of glutamate dehydrogenase 1 (Glud1) in the central nervous system affects glutamate handling without altering synaptic transmission

    DEFF Research Database (Denmark)

    Frigerio, Francesca; Karaca, Melis; De Roo, Mathias

    2012-01-01

    Glutamate dehydrogenase (GDH), encoded by GLUD1, participates in the breakdown and synthesis of glutamate, the main excitatory neurotransmitter. In the CNS, besides its primary signaling function, glutamate is also at the crossroad of metabolic and neurotransmitter pathways. Importance of brain G...... transporters and of glutamine synthetase. Present data show that the lack of GDH in the CNS modifies the metabolic handling of glutamate without altering synaptic transmission....

  4. Short-term high-fat diet primes excitatory synapses for long-term depression in orexin neurons.

    Science.gov (United States)

    Linehan, Victoria; Fang, Lisa Z; Hirasawa, Michiru

    2018-01-15

    High-fat diet consumption is a major cause of obesity. Orexin neurons are known to be activated by a high-fat diet and in turn promote further consumption of a high-fat diet. Our study shows that excitatory synapses to orexin neurons become amenable to long-term depression (LTD) after 1 week of high-fat diet feeding. However, this effect reverses after 4 weeks of a high-fat diet. This LTD may be a homeostatic response to a high-fat diet to curb the activity of orexin neurons and hence caloric consumption. Adaptation seen after prolonged high-fat diet intake may contribute to the development of obesity. Overconsumption of high-fat diets is one of the strongest contributing factors to the rise of obesity rates. Orexin neurons are known to be activated by a palatable high-fat diet and mediate the activation of the mesolimbic reward pathway, resulting in further food intake. While short-term exposure to a high-fat diet is known to induce synaptic plasticity within the mesolimbic pathway, it is unknown if such changes occur in orexin neurons. To investigate this, 3-week-old male rats were fed a palatable high-fat western diet (WD) or control chow for 1 week and then in vitro patch clamp recording was performed. In the WD condition, an activity-dependent long-term depression (LTD) of excitatory synapses was observed in orexin neurons, but not in chow controls. This LTD was presynaptic and depended on postsynaptic metabotropic glutamate receptor 5 (mGluR5) and retrograde endocannabinoid signalling. WD also increased extracellular glutamate levels, suggesting that glutamate spillover and subsequent activation of perisynaptic mGluR5 may occur more readily in the WD condition. In support of this, pharmacological inhibition of glutamate uptake was sufficient to prime chow control synapses to undergo a presynaptic LTD. Interestingly, these WD effects are transient, as extracellular glutamate levels were similar to controls and LTD was no longer observed in orexin neurons

  5. Electrical coupling and excitatory synaptic transmission between rhythmogenic respiratory neurons in the preBötzinger complex

    DEFF Research Database (Denmark)

    Rekling, J C; Shao, X M; Feldman, J L

    2000-01-01

    Breathing pattern is postulated to be generated by brainstem neurons. However, determination of the underlying cellular mechanisms, and in particular the synaptic interactions between respiratory neurons, has been difficult. Here we used dual recordings from two distinct populations of brainstem...... respiratory neurons, hypoglossal (XII) motoneurons, and rhythmogenic (type-1) neurons in the preBötzinger complex (preBötC), the hypothesized site for respiratory rhythm generation, to determine whether electrical and chemical transmission is present. Using an in vitro brainstem slice preparation from newborn...... recordings also demonstrated unidirectional excitatory chemical transmission (EPSPs of approximately 3 mV) between type-1 neurons. These data indicate that respiratory motor output from the brainstem involves gap junction-mediated current transfer between motoneurons. Furthermore, bidirectional electrical...

  6. Pharmacology of morphine and morphine-3-glucuronide at opioid, excitatory amino acid, GABA and glycine binding sites

    Energy Technology Data Exchange (ETDEWEB)

    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.).

  7. Serotonin differentially modulates excitatory and inhibitory synaptic inputs to putative sleep-promoting neurons of the ventrolateral preoptic nucleus.

    Science.gov (United States)

    Sangare, Aude; Dubourget, Romain; Geoffroy, Hélène; Gallopin, Thierry; Rancillac, Armelle

    2016-10-01

    The role of serotonin (5-HT) in sleep-wake regulation has been a subject of intense debate and remains incompletely understood. In the ventrolateral preoptic nucleus (VLPO), the main structure that triggers non-rapid eye movement (NREM) sleep, putative sleep-promoting (PSP) neurons were shown ex vivo to be either inhibited (Type-1) or excited (Type-2) by 5-HT application. To determine the complex action of this neurotransmitter on PSP neurons, we recorded spontaneous and miniature excitatory and inhibitory postsynaptic currents (sEPSCs, sIPSCs, mEPSCs and mIPSCs) in response to bath application of 5-HT. We established in mouse acute VLPO slices that 5-HT reduces spontaneous and miniature EPSC and IPSC frequencies to Type-1 neurons, whereas 5-HT selectively increases sIPSC and mIPSC frequencies to Type-2 VLPO neurons. We further determined that Type-1 neurons display a lower action potential threshold and a smaller soma size than Type-2 neurons. Finally, single-cell RT-PCR designed to identify the 13 serotonergic receptor subtypes revealed the specific mRNA expression of the 5-HT1A,B,D,F receptors by Type-1 neurons. Furthermore, the 5-HT2A-C,4,7 receptors were found to be equivalently expressed by both neuronal types. Altogether, our results establish that the excitatory and inhibitory inputs to Type-1 and Type-2 VLPO PSP neurons are differentially regulated by 5-HT. Electrophysiological, morphological and molecular differences were also identified between these two neuronal types. Our results provide new insights regarding the orchestration of sleep regulation by 5-HT release, and strongly suggest that Type-2 neurons could play a permissive role, whereas Type-1 neurons could have an executive role in sleep induction and maintenance. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Differential Alterations in Excitatory and Inhibitory Networks Involving Dentate Granule Cells Following Chronic Treatment with Distinct Classes of NMDAR Antagonists in Hippocampal Slice Cultures

    Science.gov (United States)

    2010-03-08

    synaptic Ras-GTPase activating protein TBI: traumatic brain injury TeNT: tetanus toxin TLE: temporal lobe epilepsy TEA: tetraethylammonium TTX...minimum essential medium, 25% Hank’s buffered salt solution, 25% heat-inactivated horse serum, 0.5% GlutaMax, 10 mM HEPES (all from Invitrogen...or specific blockade of neuronal glutamate release with tetanus toxin (Schiavo et al., 1992; Fellin et al., 2004). These findings showed that the

  9. 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.

  10. The neonatal development of the light flash visual evoked potential.

    Science.gov (United States)

    Kraemer, M; Abrahamsson, M; Sjöström, A

    1999-01-01

    To follow visual development longitudinally in the normal neonate using the flash visual evoked potential (VEP) and to find indications for a relationship between potential development and visual development. Twenty healthy infants, born at term, were included in the study. Flash and patterned flash VEPs were used. The first VEP was recorded the day of birth or just postnatally, and succeeding recordings were performed the following weeks and months. The data revealed different types of VEP in the neonatal period suggesting great variability in visual function on the day of birth. In the early development a potential of long latency and duration preceded the development of a more compound potential of shorter latency. The two types of responses seemed to coalesce during early development; the first late response was attenuated and was eventually integrated in the more mature VEP. At approximately five weeks of age changes in the VEP were simultaneous with the development of responsive smiling and another visual behaviour of the infants. The results showed many similarities between the VEP development in infants and in immature animals. In developing animals geniculo-cortical and extra-geniculate visual afferent pathways evoke two types of VEPs similar to those recorded in the present study. The early responses were also similar to previous recordings from children with lesions in the geniculo-striatal pathway or primary cortex. Our interpretation of the results was that the human VEP also consists of responses evoked by afferents running both in geniculo-cortical and extra-geniculate pathways and that the two types of responses could be separated in the VEP in the neonatal period. These findings are important for our understanding of conditions with a delay in visual maturation, for example intracranial haemorrhages, hydrocephalus, pre/dys-maturity and 'idiopathic' delayed visual maturation.

  11. Human auditory evoked potentials. I - Evaluation of components

    Science.gov (United States)

    Picton, T. W.; Hillyard, S. A.; Krausz, H. I.; Galambos, R.

    1974-01-01

    Fifteen distinct components can be identified in the scalp recorded average evoked potential to an abrupt auditory stimulus. The early components occurring in the first 8 msec after a stimulus represent the activation of the cochlea and the auditory nuclei of the brainstem. The middle latency components occurring between 8 and 50 msec after the stimulus probably represent activation of both auditory thalamus and cortex but can be seriously contaminated by concurrent scalp muscle reflex potentials. The longer latency components occurring between 50 and 300 msec after the stimulus are maximally recorded over fronto-central scalp regions and seem to represent widespread activation of frontal cortex.

  12. The division of attention and the human auditory evoked potential

    Science.gov (United States)

    Hink, R. F.; Van Voorhis, S. T.; Hillyard, S. A.; Smith, T. S.

    1977-01-01

    The sensitivity of the scalp-recorded, auditory evoked potential to selective attention was examined while subjects responded to stimuli presented to one ear (focused attention) and to both ears (divided attention). The amplitude of the N1 component was found to be largest to stimuli in the ear upon which attention was to be focused, smallest to stimuli in the ear to be ignored, and intermediate to stimuli in both ears when attention was divided. The results are interpreted as supporting a capacity model of attention.

  13. Brain stem auditory evoked responses in human infants and adults

    Science.gov (United States)

    Hecox, K.; Galambos, R.

    1974-01-01

    Brain stem evoked potentials were recorded by conventional scalp electrodes in infants (3 weeks to 3 years of age) and adults. The latency of one of the major response components (wave V) is shown to be a function both of click intensity and the age of the subject; this latency at a given signal strength shortens postnatally to reach the adult value (about 6 msec) by 12 to 18 months of age. The demonstrated reliability and limited variability of these brain stem electrophysiological responses provide the basis for an optimistic estimate of their usefulness as an objective method for assessing hearing in infants and adults.

  14. The Electrically Evoked Compound Action Potential: From Laboratory to Clinic.

    Science.gov (United States)

    He, Shuman; Teagle, Holly F B; Buchman, Craig A

    2017-01-01

    The electrically evoked compound action potential (eCAP) represents the synchronous firing of a population of electrically stimulated auditory nerve fibers. It can be directly recorded on a surgically exposed nerve trunk in animals or from an intra-cochlear electrode of a cochlear implant. In the past two decades, the eCAP has been widely recorded in both animals and clinical patient populations using different testing paradigms. This paper provides an overview of recording methodologies and response characteristics of the eCAP, as well as its potential applications in research and clinical situations. Relevant studies are reviewed and implications for clinicians are discussed.

  15. Temporal suppression and augmentation of click-evoked otoacoustic emissions

    DEFF Research Database (Denmark)

    Verhulst, Sarah; Harte, James; Dau, Torsten

    2008-01-01

    This study investigates and models temporal suppression of click-evoked otoacoustic emissions (CEOAEs). This suppression-effect is created when a suppressor-click is presented close in time to a test-click. The analysis was carried out for short time-frames of short- and long-latency CEOAEs...... suppression is present in all CEOAEs for inter-click intervals (ICIs) less than 8 ms. The long-latency CEOAEs showed augmentation (i.e., negative suppression) for ICIs of 6-7 ms which was not reported for the short-latency CEOAE at these ICIs. A phenomenological approach is adopted here to explain both...

  16. Estimation of evoked potentials using total least squares prony technique.

    Science.gov (United States)

    Akkin, T; Saliu, S

    1998-09-01

    The authors investigate the applicability of Prony modelling to the estimation of evoked potentials. Four types of total least squares (TLS) model are considered and their optimal parameters are defined based on ten visual averaged EPs. Simulations with various signal and noise characteristics show that the TLS-Prony estimation is superior to averaging for two of the models, namely the unconstrained and the stable models. Application of the TLS-Prony estimator as a post-processor to moderate averaging allows a reduction in the number of responses averaged, or equivalently of recording time, by a factor of two.

  17. Neuronal Rac1 is required for learning-evoked neurogenesis

    DEFF Research Database (Denmark)

    Haditsch, Ursula; Anderson, Matthew P; Freewoman, Julia

    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...

  18. 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 poten...

  19. Pharmacological characterization of human excitatory amino acid transporters EAAT1, EAAT2 and EAAT3 in a fluorescence-based membrane potential assay

    DEFF Research Database (Denmark)

    Jensen, Anders A.; Bräuner-Osborne, Hans

    2004-01-01

    We have expressed the human excitatory amino acid transporters EAAT1, EAAT2 and EAAT3 stably in HEK293 cells and characterized the transporters pharmacologically in a conventional [(3) H]-d-aspartate uptake assay and in a fluorescence-based membrane potential assay, the FLIPR Membrane Potential (...

  20. 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

  1. Clinical application of visual evoked potential in orbital cellulitis of infants

    Directory of Open Access Journals (Sweden)

    Xiao-Juan Jing

    2014-07-01

    Full Text Available AIM: To explore the visual evoked potential in infantile orbital cellulitis' clinical applications by monitoring the visual evoked potential changes in infantile orbital cellulitis before, during and after treatment.METHODS: Twenty-three cases of CT diagnosed single orbital cellulitis were examined by the visual evoked potentials. The affected eyes as observation group, and healthy eyes as control group. Comparative observation of visual evoked potential changes in amplitude and incubation period before, during and after the treatment. RESULTS: Compared with the control group, the observation group's visual evoked potential changes included reduced amplitude, extended incubation period. With the treatment progress, the observation group had gradual increase in amplitude, gradual reduction in incubation period. CONCLUSION: In infantile orbital cellulitis, the use of visual evoked potentials is a simple, feasible and effective method to monitoring the visual function during the treatment.

  2. Magnetic fields evoked by speech sounds in preschool children.

    Science.gov (United States)

    Pihko, Elina; Kujala, Teija; Mickos, Annika; Antell, Henrik; Alku, Paavo; Byring, Roger; Korkman, Marit

    2005-01-01

    Our objective was to study how well the auditory evoked magnetic fields (EF) reflect the behavioral discrimination of speech sounds in preschool children, and if they reveal the same information as simultaneously recorded evoked potentials (EP). EFs and EPs were recorded in 11 preschool children (mean age 6 years 9 months) using an oddball paradigm with two sets of speech stimuli consisting both of one standard and two deviants. After the brain activity recording, children were tested on behavioural discrimination of the same stimuli presented in pairs. There was a mismatch negativity (MMN) calculated from difference curves and its magnetic counterpart MMNm measured from the original responses only to those deviants, which were behaviourally easiest to discriminate from the standards. In addition, EF revealed significant differences between the locations of the activation depending on the hemisphere and stimulus properties. EF, in addition to reflecting the sound-discrimination accuracy in a similar manner as EP, also reflected the spatial differences in activation of the temporal lobes. These results suggest that both EPs and EFs are feasible for investigating the neural basis of sound discrimination in young children. The recording of EFs with its high spatial resolution reveals information on the location of the activated neural sources.

  3. A New Measure for Monitoring Intraoperative Somatosensory Evoked Potentials

    Science.gov (United States)

    Jin, Seung-Hyun; Kim, Jeong Eun; Choi, Young Doo

    2014-01-01

    Objective To propose a new measure for effective monitoring of intraoperative somatosensory evoked potentials (SEP) and to validate the feasibility of this measure for evoked potentials (EP) and single trials with a retrospective data analysis study. Methods The proposed new measure (hereafter, a slope-measure) was defined as the relative slope of the amplitude and latency at each EP peak compared to the baseline value, which is sensitive to the change in the amplitude and latency simultaneously. We used the slope-measure for EP and single trials and compared the significant change detection time with that of the conventional peak-to-peak method. When applied to single trials, each single trial signal was processed with optimal filters before using the slope-measure. In this retrospective data analysis, 7 patients who underwent cerebral aneurysm clipping surgery for unruptured aneurysm middle cerebral artery (MCA) bifurcation were included. Results We found that this simple slope-measure has a detection time that is as early or earlier than that of the conventional method; furthermore, using the slope-measure in optimally filtered single trials provides warning signs earlier than that of the conventional method during MCA clipping surgery. Conclusion Our results have confirmed the feasibility of the slope-measure for intraoperative SEP monitoring. This is a novel study that provides a useful measure for either EP or single trials in intraoperative SEP monitoring. PMID:25628803

  4. A wireless system for monitoring transcranial motor evoked potentials.

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    Farajidavar, Aydin; Seifert, Jennifer L; Bell, Jennifer E S; Seo, Young-Sik; Delgado, Mauricio R; Sparagana, Steven; Romero, Mario I; Chiao, J-C

    2011-01-01

    Intraoperative neurophysiological monitoring (IONM) is commonly used as an attempt to minimize neurological morbidity from operative manipulations. The goal of IONM is to identify changes in the central and peripheral nervous system function prior to irreversible damage. Intraoperative monitoring also has been effective in localizing anatomical structures, including peripheral nerves and sensorimotor cortex, which helps guide the surgeon during dissection. As part of IONM, transcranial motor evoked potentials (TcMEPs), and somatosensory evoked potentials (SSEPs) are routinely monitored. However, current wired systems are cumbersome as the wires contribute to the crowded conditions in the operating room and in doing so not only it limits the maneuverability of the surgeon and assistants, but also places certain demand in the total anesthesia required during surgery, due to setup preoperative time needed for proper electrode placement, due to the number and length of the wires, and critical identification of the lead wires needed for stimulation and recording. To address these limitations, we have developed a wireless TcMEP IONM system as a first step toward a multimodality IONM system. Bench-top and animal experiments in rodents demonstrated that the wireless method reproduced with high fidelity, and even increased the frequency bandwidth of the TcMEP signals, compared to wired systems. This wireless system will reduce the preoperative time required for IONM setup, add convenience for surgical staff, and reduce wire-related risks for patients during the operation.

  5. Evoked brain potentials and disability in brain-damaged patients.

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    Rappaport, M; Hall, K; Hopkins, K; Belleza, T; Berrol, S; Reynolds, G

    1977-08-01

    Various measures of evoked brain potential abnormality (EPA) were correlated with disability ratings (DR) for 35 brain-damaged patients. EPA data consisted of judgements of abnormality of ipsilateral, contralateral and bilateral responses to auditory and visual stimuli reflecting activity in the brain stem, subcortex and cortex. DR data were obtained from a scale developed for this study to quantize and categorize patients with a wide range of disabilities from coma to normal functioning. EPA scores based on visual and auditory cortical responses showed significantly positive correlations with degree of disability. Visual response correlation was .49, auditory .38 and combined visual and auditory .51. It was concluded that EPA measures can reflect disability independently of clinical information. They are useful in assessing brain function in general and, specifically, in assessing impairment of sensory function. The evoked potential technique was particularly useful in patients who were not able to participate fully in their own examination. There were indications that the technique may also be valuable in monitoring progress and in predicting clinical outcome in brain-damaged patients.

  6. Somatosensory evoked potentials in children with severe head trauma.

    Science.gov (United States)

    Schalamon, Johannes; Singer, Georg; Kurschel, Senta; Höllwarth, Michael E

    2005-07-01

    We evaluated the predictive value of somatosensory evoked potentials (SEP) in a series of children with severe traumatic brain injury (TBI). The prospective clinical investigation was performed in a Level I paediatric trauma centre. We included 26 consecutive comatose paediatric patients aged from 1 month to 17 years (median age 11 years) following severe TBI (initial Glasgow Coma Score (GCS) 8 or below). Besides SEP recordings, the intracranial pressure and the results of an initial cranial CT scan were filed. The Glasgow Outcome Scale (GOS) was used to assess outcome at discharge. Thirteen children had normal SEP measurements, three patients had abnormal SEP recordings and a cortical response was bilaterally absent in ten children. Out of 26 children, 10 died whereas two remained in a persistent vegetative state. Only one child suffered from significant neurological deficits (GOS 3) at discharge. Seven patients survived with a GOS of 4 and six children survived without neurological impairment (GOS 5). Normal SEP indicated a favourable outcome in most children but did not rule out the occurrence of death, while absence of SEP was related to unfavourable outcome in all cases. Measurement of somatosensory evoked potentials provides valuable data for determining the prognosis at early coma stages. Our data show that an unfavourable outcome can be predicted with higher precision than a favourable outcome.

  7. Unwanted sexual experiences and cognitive appraisals that evoke mental contamination.

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    Ishikawa, Ryotaro; Kobori, Osamu; Shimizu, Eiji

    2015-01-01

    Mental contamination is a psychological sense of contamination that involves an internal, emotional feeling of dirtiness that may be evoked by unwanted thoughts and images, such as sexual assaults. This study aimed to investigate which types of unwanted sexual experiences evoke the strongest mental contamination, and to test the hypothesis that cognitive appraisals of an unwanted sexual experience predict indices of mental contamination (i.e. feeling of dirtiness, urge to wash, internal negative emotions, and external negative emotions). 148 female participants were asked to recall their most distressing unwanted sexual experiences. Indices of mental contamination and cognitive appraisals of the experience were then assessed. Our findings indicated that individuals recalling experiences related to rape felt more intense feelings of dirtiness than individuals recalling other types of unwanted sexual experience, such as verbal sexual assault, visual sexual assault, and forcible touching/frottage. In addition, hierarchical regression analyses demonstrated that a cognitive appraisal of perceived violation predicted all of the indices of mental contamination after controlling anxiety, depression, and fear of contact contamination. The present study demonstrated that an individual is at greatest risk of mental contamination if she has experienced rape/attempted rape, and if she makes a cognitive appraisal of violation regarding the incident.

  8. Synaptically evoked glutamate transporter currents in Spinal Dorsal Horn Astrocytes

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    Dougherty Patrick M

    2009-07-01

    Full Text Available Abstract Background Removing and sequestering synaptically released glutamate from the extracellular space is carried out by specific plasma membrane transporters that are primarily located in astrocytes. Glial glutamate transporter function can be monitored by recording the currents that are produced by co-transportation of Na+ ions with the uptake of glutamate. The goal of this study was to characterize glutamate transporter function in astrocytes of the spinal cord dorsal horn in real time by recording synaptically evoked glutamate transporter currents. Results Whole-cell patch clamp recordings were obtained from astrocytes in the spinal substantia gelatinosa (SG area in spinal slices of young adult rats. Glutamate transporter currents were evoked in these cells by electrical stimulation at the spinal dorsal root entry zone in the presence of bicuculline, strychnine, DNQX and D-AP5. Transporter currents were abolished when synaptic transmission was blocked by TTX or Cd2+. Pharmacological studies identified two subtypes of glutamate transporters in spinal astrocytes, GLAST and GLT-1. Glutamate transporter currents were graded with stimulus intensity, reaching peak responses at 4 to 5 times activation threshold, but were reduced following low-frequency (0.1 – 1 Hz repetitive stimulation. Conclusion These results suggest that glutamate transporters of spinal astrocytes could be activated by synaptic activation, and recording glutamate transporter currents may provide a means of examining the real time physiological responses of glial cells in spinal sensory processing, sensitization, hyperalgesia and chronic pain.

  9. Nostalgia-Evoked Inspiration: Mediating Mechanisms and Motivational Implications.

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    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.

  10. Visual evoked potentials, reaction times and eye dominance in cricketers.

    Science.gov (United States)

    Thomas, N G; Harden, L M; Rogers, G G

    2005-09-01

    Few studies have examined the physiology of cricket, including the difference in ability between batsmen to make controlled contact with a ball bowled at high speed. We therefore measured visual evoked potentials and choice reaction times with dominant eyes, non-dominant eyes, and both eyes together, in 15 elite batsmen and 10 elite bowlers (aged 20.9 SD 1.9 years) and 9 control subjects (aged 20.2 SD 1.5 years). The latency and amplitude of waves N70, P100 and N145 were determined for each visual evoked potential (VEP). In addition interpeak latencies and peak to peak amplitudes were measured. The subjects also completed a choice reaction test to a visual stimulus. We found that cricketers were not more likely to have crossed dominance (dominant eye contralateral to dominant hand) than controls. Cricketers had a faster latency for VEP wave N70 than controls (p=0.03). However reaction time was not different between cricketers and the control group. Across all subjects, in comparison to monocular testing, binocular testing led to a faster choice reaction time (p=0.02) and larger amplitudes of VEP wave N70 (p=0.01). Visual processing during the first 100(-1)50 ms of the balls flight together with binocular vision facilitates retinal activation in talented cricketers.

  11. Cortical Auditory-Evoked Potential and Behavioral Evidence for Differences in Auditory Processing between Good and Poor Readers.

    Science.gov (United States)

    Barker, Matthew D; Kuruvilla-Mathew, Abin; Purdy, Suzanne C

    2017-06-01

    the poor readers. The current study found altered AP in poor readers using behavioral Feather Squadron measures and speech-evoked cortical potentials. These results provide further evidence that intact central auditory function is fundamental for reading development.

  12. Surviving mossy cells enlarge and receive more excitatory synaptic input in a mouse model of temporal lobe epilepsy.

    Science.gov (United States)

    Zhang, Wei; Thamattoor, Ajoy K; LeRoy, Christopher; Buckmaster, Paul S

    2015-05-01

    Numerous hypotheses of temporal lobe epileptogenesis have been proposed, and several involve hippocampal mossy cells. Building on previous hypotheses we sought to test the possibility that after epileptogenic injuries surviving mossy cells develop into super-connected seizure-generating hub cells. If so, they might require more cellular machinery and consequently have larger somata, elongate their dendrites to receive more synaptic input, and display higher frequencies of miniature excitatory synaptic currents (mEPSCs). To test these possibilities pilocarpine-treated mice were evaluated using GluR2-immunocytochemistry, whole-cell recording, and biocytin-labeling. Epileptic pilocarpine-treated mice displayed substantial loss of GluR2-positive hilar neurons. Somata of surviving neurons were 1.4-times larger than in controls. Biocytin-labeled mossy cells also were larger in epileptic mice, but dendritic length per cell was not significantly different. The average frequency of mEPSCs of mossy cells recorded in the presence of tetrodotoxin and bicuculline was 3.2-times higher in epileptic pilocarpine-treated mice as compared to controls. Other parameters of mEPSCs were similar in both groups. Average input resistance of mossy cells in epileptic mice was reduced to 63% of controls, which is consistent with larger somata and would tend to make surviving mossy cells less excitable. Other intrinsic physiological characteristics examined were similar in both groups. Increased excitatory synaptic input is consistent with the hypothesis that surviving mossy cells develop into aberrantly super-connected seizure-generating hub cells, and soma hypertrophy is indirectly consistent with the possibility of axon sprouting. However, no obvious evidence of hyperexcitable intrinsic physiology was found. Furthermore, similar hypertrophy and hyper-connectivity has been reported for other neuron types in the dentate gyrus, suggesting mossy cells are not unique in this regard. Thus

  13. 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

  14. The Intraoperative Effect of Methadone on Somatosensory Evoked Potentials.

    Science.gov (United States)

    Higgs, Maureen; Hackworth, Robert J; John, King; Riffenburgh, Robert; Tomlin, Jeffrey; Wamsley, Brian

    2017-04-01

    Evoked potentials (EP), both somatosensory evoked potentials (SSEP) and transcranial motor evoked potentials (TcMEP), are often used during complex spine surgery to monitor the integrity of spinal pathways during operations in or around the spine. Changes in these monitored EP signals (increased latency and decreased amplitude) may result from ischemia, direct surgical injury, changes in blood pressure, hypoxia, changes in CO2 tension, and anesthetic agents. Typically, a clinically significant change for SSEPs is defined as an increase in latency >10% or a decrease of amplitude >50%. A clinically significant change for TcMEPs is much more complex but is also described in terms of large signal loss or decrease. Opioids have been shown to both increase latency and decrease the amplitude of SSEPs, although this change is usually not clinically significant. There has been a renewed interest in methadone for use in spine and other complex surgeries. However, the effect of methadone on intraoperative monitoring of SSEPs and TcMEPs is unknown. We present the first study to directly look at the effects of methadone on SSEP and TcMEP monitoring during complex spine surgery. The goal of this study was to observe the effect of methadone on an unrandomized set of patients. The primary endpoint was methadone's effect on SSEPs, and the secondary endpoint was methadone's effect on TcMEPs. Adult patients undergoing spine surgery requiring intraoperative neuromonitoring were induced with general anesthesia and had a baseline set of SSEPs and TcMEPs recorded. Next, methadone dosed 0.2 mg/kg/lean body weight was given. Repeat SSEPs and TcMEPs were recorded at 5, 10, and 15 minutes, with the timing based on distribution half-life of methadone between 6 and 8 minutes. Postoperatively, adverse events from methadone administration were collected. There was a statistically significant difference found in SSEPs for N20 latency (95% confidence interval [CI], 0.17-0.53; P=0.028), P37 latency

  15. SOMATOSENSORY EVOKED POTENTIALS IN DIABETES MELLITUS TYPE - 2

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    Rekha

    2015-10-01

    Full Text Available Diabetes mellitus is the most common metabolic disorder affecting majority of population. It is estimated that over 400 million people throughout the world have diabetes. It has progressed to be a pandemic from an epidemic causing morbidity and mortality in the population. Among the many complications of diabetes, diabetic neuropathies contribute majorly to the morbidity associated with the disease. Axonal conduction is affected by elevated levels of protein kinase c causing neuronal ischemia; decreased ce llular myoinositol affecting sodium potassium ATPase pump leads to decreased nerve conduction; Somatosensory E voked P otentials (SSEPs reflect the activity of somatosensory pathways mediated through the dorsal columns of the spinal cord and the specific so matosensory cortex. Recording of Somatosensory Evoked Potentials in diabetics is done to assess the sensory involvement of spinal cord. Presence of SEPs provides clear evidence for axonal continuity and by using different stimulation sites, the rate of reg eneration can be determined. Both onset and peak latencies of all SEP components are prolonged in patients with diabetes. Present study is done to compare somatosensory evoked potentials in diabetics and normal subjects. MATERIALS AND METHOD S: The present study was undertaken at the Upgraded Department of Physiology, Osmania Medical College, Koti, Hyderabad. The study was conducted on subjects, both male and female in the age group of 45 to 55 years, suffering from type II diabetes excluding other neurologi cal disorders. Non - invasive method of estimation of nerve conduction studies using SFEMG/EP — Electromyography or evoked potential system (Nicolet systems — USA using surface electrodes with automated computerized monitor attached with printer is used. RESUL TS : ANOVA showed statistically significant N9 latency (right & left sides. Latencies of all the components of SSEPs were more significant than amplitudes in Diabetic

  16. Assessment of visual disability using visual evoked potentials

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    Jeon Jihoon

    2012-08-01

    Full Text Available Abstract Background 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. Methods 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. Results 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

  17. Theta Burst Stimulation of the Cerebellum Modifies the TMS-Evoked N100 Potential, a Marker of GABA Inhibition.

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    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.

  18. Sound-Evoked Biceps Myogenic Potentials Reflect Asymmetric Vestibular Drive to Spastic Muscles in Chronic Hemiparetic Stroke Survivors.

    Science.gov (United States)

    Miller, Derek M; Rymer, William Z

    2017-01-01

    Aberrant vestibular nuclear function is proposed to be a principle driver of limb muscle spasticity after stroke. We sought to determine whether altered cortical modulation of descending vestibulospinal pathways post-stroke could impact the excitability of biceps brachii motoneurons. Twelve chronic hemispheric stroke survivors aged 46-68 years were enrolled. Sound evoked biceps myogenic potentials (SEBMPs) were recorded from the spastic and contralateral biceps muscles using surface EMG electrodes. We assessed the impact of descending vestibulospinal pathways on biceps muscle activity and evaluated the relationship between vestibular function and the severity of spasticity. Spastic SEBMP responses were recorded in 11/12 subjects. Almost 60% of stroke subjects showed evoked responses solely on the spastic side. These data strongly support the idea that vestibular drive is asymmetrically distributed to biceps motoneuron pools in hemiparetic spastic stroke survivors. This abnormal vestibular drive is very likely to be a factor mediating the striking differences in motoneuron excitability between the clinically affected and clinically spared sides. This study extends our previous observations on vestibular nuclear changes following hemispheric stroke and potentially sheds light on the underlying mechanisms of post-stroke spasticity.

  19. The insulin-mediated modulation of visually evoked magnetic fields is reduced in obese subjects.

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    Martina Guthoff

    Full Text Available BACKGROUND: Insulin is an anorexigenic hormone that contributes to the termination of food intake in the postprandial state. An alteration in insulin action in the brain, named "cerebral insulin resistance", is responsible for overeating and the development of obesity. METHODOLOGY/PRINCIPAL FINDINGS: To analyze the direct effect of insulin on food-related neuronal activity we tested 10 lean and 10 obese subjects. We conducted a magnetencephalography study during a visual working memory task in both the basal state and after applying insulin or placebo spray intranasally to bypass the blood brain barrier. Food and non-food pictures were presented and subjects had to determine whether or not two consecutive pictures belonged to the same category. Intranasal insulin displayed no effect on blood glucose, insulin or C-peptide concentrations in the periphery; however, it led to an increase in the components of evoked fields related to identification and categorization of pictures (at around 170 ms post stimuli in the visual ventral stream in lean subjects when food pictures were presented. In contrast, insulin did not modulate food-related brain activity in obese subjects. CONCLUSIONS/SIGNIFICANCE: We demonstrated that intranasal insulin increases the cerebral processing of food pictures in lean whereas this was absent in obese subjects. This study further substantiates the presence of a "cerebral insulin resistance" in obese subjects and might be relevant in the pathogenesis of obesity.

  20. Contribution of glutamatergic systems in locus coeruleus to nucleus paragigantocellularis stimulation-evoked behavior.

    Science.gov (United States)

    Liu, N; Ho, I K; Rockhold, R W

    1999-08-01

    The role of extracellular glutamate, within the locus coeruleus, in mediation of the behavioral signs elicited by electrical stimulation of the nucleus paragigantocellularis (PGi) was investigated in conscious, opioid-naive rats. Each rat was prepared with a chronically implanted unilateral electrode within the PGi and a microdialysis guide cannula directed at the ipsilateral locus coeruleus. Opioid withdrawal-like behaviors (rearing, teeth-chattering, wet-dog shakes, etc.) and increases in extracellular glutamate concentrations within the locus coeruleus were evoked, in a frequency-dependent (0.5-50 Hz) manner, during PGi stimulation. Reverse dialysis perfusion of the locus coeruleus with the nonspecific glutamate receptor antagonist, kynurenic acid (0.1, 1 mM), reduced the intensity of stimulation-induced behaviors by roughly 50%, but had no effect on the corresponding increases in glutamate concentrations. Perfusion of the locus coeruleus with the glutamate transporter inhibitor, L-trans-pyrrolidine dicarboxylic acid, at 1, but not at 0.1, mM significantly increased glutamate levels in dialysates. Neither concentration of the transporter inhibitor altered the behavioral score. The results indicate that the opioid withdrawal-like behaviors elicited by electrical stimulation of the brainstem at the site of the PGi are positively correlated with locus coeruleus levels of glutamate, and suggest further that the behaviors are partially mediated by release of glutamate within the locus coeruleus or its immediate vicinity.

  1. Effect of caffeine on cervical vestibular-evoked myogenic potential in healthy individuals

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    Ana Maria Almeida de Sousa

    2014-06-01

    Full Text Available INTRODUCTION: Caffeine is the most common psychoactive drug in use around the world and is found at different concentrations in a variety of common food items. Clinically, a strong association between caffeine consumption and diseases of the vestibular system has been established. Cervical vestibular-evoked myogenic potential (cVEMP is an electrophysiological test that is used to assess the sacculocollic pathway by measuring changes in the vestialibulocollic reflex. AIM: The present study aimed to evaluate the effect of an acute dose of caffeine on the vestibulocollic reflex by using cVEMP. METHOD: A prospective experimental study was performed in which healthy volunteers were submitted to the test before and after the intake of 420 mg of caffeine. The following parameters were compared: p13 and n23 latencies and p13-n23 amplitude. RESULT: No statistically significant difference was found in the test results before and after caffeine use. CONCLUSION: The vestibulocollic reflex is not altered by caffeine intake.

  2. Spontaneous activity forms a foundation for odor-evoked activation maps in the rat olfactory bulb.

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    Thompson, Garth J; Sanganahalli, Basavaraju G; Baker, Keeley L; Herman, Peter; Shepherd, Gordon M; Verhagen, Justus V; Hyder, Fahmeed

    2018-01-25

    Fluctuations in spontaneous activity have been observed by many neuroimaging techniques, but because these resting-state changes are not evoked by stimuli, it is difficult to determine how they relate to task-evoked activations. We conducted multi-modal neuroimaging scans of the rat olfactory bulb, both with and without odor, to examine interaction between spontaneous and evoked activities. Independent component analysis of spontaneous fluctuations revealed resting-state networks, and odor-evoked changes revealed activation maps. We constructed simulated activation maps using resting-state networks that were highly correlated to evoked activation maps. Simulated activation maps derived by intrinsic optical signal (IOS), which covers the dorsal portion of the glomerular sheet, significantly differentiated one odor's evoked activation map from the other two. To test the hypothesis that spontaneous activity of the entire glomerular sheet is relevant for representing odor-evoked activations, we used functional magnetic resonance imaging (fMRI) to map the entire glomerular sheet. In contrast to the IOS results, the fMRI-derived simulated activation maps significantly differentiated all three odors' evoked activation maps. Importantly, no evoked activation maps could be significantly differentiated using simulated activation maps produced using phase-randomized resting-state networks. Given that some highly organized resting-state networks did not correlate with any odors' evoked activation maps, we posit that these resting-state networks may characterize evoked activation maps associated with odors not studied. These results emphasize that fluctuations in spontaneous activity are relevant for active processing, signifying the relevance of resting-state mapping to functional neuroimaging. Copyright © 2018. Published by Elsevier Inc.

  3. Sensorimotor incongruence alters limb perception and movement.

    Science.gov (United States)

    Osumi, Michihiro; Nobusako, Satoshi; Zama, Takuro; Taniguchi, Megumi; Shimada, Sotaro; Morioka, Shu

    2017-09-21

    Altered limb ownership or heaviness has been observed in patients with hemiplegia, chronic pain, and several other conditions. Although these sensations are thought to be caused by sensorimotor incongruence, few studies have systematically verified this relationship. In addition, it remains unclear whether these subjective sensations affect movement execution. In a psychophysical experiment, we systematically investigated the relationships between sensorimotor integration and subjective limb perception, such as sense of ownership/heaviness, and verified the relationship between subjective limb perception and movement execution. Thirty-nine healthy participants were enrolled, and a visual feedback delay system was used to systematically evoke sensorimotor incongruence. Participants periodically flexed and extended their wrist while seeing a delayed image of their hand under five delay conditions (0, 150, 250, 350, 600ms). During wrist movement, electromyography (EMG) activity in flexor carpi radialis (FCR) was recorded. Also, to analyze the change in muscle activity and movement speed, the values of integral and peak frequency were calculated. To record changes in the subjective limb perception of the altered limb ownership and heaviness, we used a 7-point Likert scale for each participant. We found that altered ownership and heaviness increased with increasing feedback delay. Also, muscle activity and movement speed decreased with visual feedback delay. There was no significant correlation between subjective altered limb perception (i.e., altered limb ownership and heaviness) and muscle activity or movement speed. We systematically demonstrated that limb ownership, heaviness, muscle activation and movement speed were altered by sensorimotor incongruence. However, our study did not reveal the relationships between these factors. These results indicate the existence of different mechanisms governing subjective limb perception and movement execution. In the future, we

  4. Multimodality evoked potentials in HTLV-I associated myelopathy.

    Science.gov (United States)

    Kakigi, R; Shibasaki, H; Kuroda, Y; Endo, C; Oda, K; Ikeda, A; Hashimoto, K

    1988-08-01

    Multimodality evoked potentials (EPs) consisting of somatosensory EPs (SEPs), visual EPs (VEPs) and brainstem auditory EPs (BAEPs) were studied in 16 cases with HTLV-I associated myelopathy (HAM). Median nerve SEPs were normal in all cases. In posterior tibial nerve SEPs, the potential recorded at the 12th thoracic spinal process was normal in every case but cortical components were significantly prolonged in 10 cases, although five of these showed no sensory impairment. BAEPs were normal in every case whose hearing was intact, but VEPs were abnormal in two cases whose visual acuities were normal. The present results in HAM indicate predominant lesion in the thoracic cord, and might also suggest some subclinical lesion in the visual pathway.

  5. Temporal suppression and augmentation of click-evoked otoacoustic emissions

    DEFF Research Database (Denmark)

    Verhulst, Sarah; Harte, James; Dau, Torsten

    2008-01-01

    This study investigates temporal suppression of click-evoked otoacoustic emissions (CEOAEs), occurring when a suppressor-click is presented close in time to a test-click (e.g. 0-8ms). Various temporal suppression methods for examining temporal changes in cochlear compression were evaluated...... and measured here for seven subjects, both for short- and long-latency CEOAEs. Long-latency CEOAEs (duration >20ms) typically indicate the presence of synchronised spontaneous otoacoustic emissions (SSOAEs). Temporal suppression can only be linked to changes in CEOAE-compression if the suppressor-click affects...... the CEOAE magnitude. Phase changes induced by the suppressor-click were shown to bias suppression in two ways: (i) when a specific asymmetric measurement method was used and (ii) when synchronisation between the CEOAE and the click-stimuli was incomplete. When such biases were eliminated, temporal...

  6. Auditory evoked responses upon awakening from sleep in human subjects.

    Science.gov (United States)

    Ferrara, M; De Gennaro, L; Ferlazzo, F; Curcio, G; Barattucci, M; Bertini, M

    2001-09-14

    The hypothesis that a state of hypoarousal upon awakening should lead to a decrease in amplitude and an increase in latency of the N1-P2 components of the Auditory Evoked Potentials (AEPs) as compared to presleep wakefulness levels, was evaluated after two nocturnal awakenings and after the final morning awakening from a 7.5-h night of sleep. The amplitude of the N1-P2 complex was reduced upon awakening as compared to presleep wakefulness levels, but only following the first nocturnal awakening, scheduled after the first 2 h of sleep. This result is interpreted as indicating a link between slow wave sleep amount, mainly present during the first part of the night, and lowered levels of brain activation upon awakening. The reaction times, recorded concomitantly to AEPs, were more sensitive to the negative effects of sleep inertia.

  7. Auditory evoked field measurement using magneto-impedance sensors

    Energy Technology Data Exchange (ETDEWEB)

    Wang, K., E-mail: o-kabou@echo.nuee.nagoya-u.ac.jp; Tajima, S.; Song, D.; Uchiyama, T. [Graduate School of Engineering, Nagoya University, Nagoya (Japan); Hamada, N.; Cai, C. [Aichi Steel Corporation, Tokai (Japan)

    2015-05-07

    The magnetic field of the human brain is extremely weak, and it is mostly measured and monitored in the magnetoencephalography method using superconducting quantum interference devices. In this study, in order to measure the weak magnetic field of the brain, we constructed a Magneto-Impedance sensor (MI sensor) system that can cancel out the background noise without any magnetic shield. Based on our previous studies of brain wave measurements, we used two MI sensors in this system for monitoring both cerebral hemispheres. In this study, we recorded and compared the auditory evoked field signals of the subject, including the N100 (or N1) and the P300 (or P3) brain waves. The results suggest that the MI sensor can be applied to brain activity measurement.

  8. The effect of a concurrent cognitive task on cortical potentials evoked by unpredictable balance perturbations

    Directory of Open Access Journals (Sweden)

    Staines W Richard

    2004-05-01

    Full Text Available Abstract Background Although previous studies suggest that postural control requires attention and other cognitive resources, the central mechanisms responsible for this relationship remain unclear. To address this issue, we examined the effects of altered attention on cortical activity and postural responses following mechanical perturbations to upright stance. We hypothesized that cortical activity would be attenuated but not delayed when mechanical perturbations were applied during a concurrent performance of a cognitive task (i.e. when attention was directed away from the perturbation. We also hypothesized that these cortical changes would be accompanied by alterations in the postural response, as evidenced by increases in the magnitude of anteroposterior (AP centre of pressure (COP peak displacements and tibialis anterior (TA muscle activity. Healthy young adults (n = 7 were instructed to continuously track (cognitive task or not track (control task a randomly moving visual target using a hand-held joystick. During each of these conditions, unpredictable translations of a moving floor evoked cortical and postural responses. Scalp-recorded cortical activity, COP, and TA electromyographic (EMG measures were collected. Results Results revealed a significant decrease in the magnitude of early cortical activity (the N1 response, the first negative peak after perturbation onset during the tracking task compared to the control condition. More pronounced AP COP peak displacements and EMG magnitudes were also observed for the tracking task and were possibly related to changes in the N1 response. Conclusion Based on previous notions that the N1 response represents sensory processing of the balance disturbance, we suggest that the attenuation of the N1 response is an important central mechanism that may provide insight into the relationship between attention and postural control.

  9. Facilitation and refractoriness of the electrically evoked compound action potential.

    Science.gov (United States)

    Hey, Matthias; Müller-Deile, Joachim; Hessel, Horst; Killian, Matthijs

    2017-11-01

    In this study we aim to resolve the contributions of facilitation and refractoriness at very short pulse intervals. Measurements of the refractory properties of the electrically evoked compound action potential (ECAP) of the auditory nerve in cochlear implant (CI) users at inter pulse intervals below 300 μs are influenced by facilitation and recovery effects. ECAPs were recorded using masker pulses with a wide range of current levels relative to the probe pulse levels, for three suprathreshold probe levels and pulse intervals from 13 to 200 μs. Evoked potentials were measured for 21 CI patients by using the masked response extraction artifact cancellation procedure. During analysis of the measurements the stimulation current was not used as absolute value, but in relation to the patient's individual ECAP threshold. This enabled a more general approach to describe facilitation as a probe level independent effect. Maximum facilitation was found for all tested inter pulse intervals at masker levels near patient's individual ECAP threshold, independent from probe level. For short inter pulse intervals an increased N1P1 amplitude was measured for subthreshold masker levels down to 120 CL below patient's individual ECAP threshold in contrast to the recreated state. ECAPs recorded with inter pulse intervals up to 200 μs are influenced by facilitation and recovery. Facilitation effects are most pronounced for masker levels at or below ECAP threshold, while recovery effects increase with higher masker levels above ECAP threshold. The local maximum of the ECAP amplitude for masker levels around ECAP threshold can be explained by the mutual influence of maximum facilitation and minimal refractoriness. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  10. Accuracy of measurement in electrically evoked compound action potentials.

    Science.gov (United States)

    Hey, Matthias; Müller-Deile, Joachim

    2015-01-15

    Electrically evoked compound action potentials (ECAP) in cochlear implant (CI) patients are characterized by the amplitude of the N1P1 complex. The measurement of evoked potentials yields a combination of the measured signal with various noise components but for ECAP procedures performed in the clinical routine, only the averaged curve is accessible. To date no detailed analysis of error dimension has been published. The aim of this study was to determine the error of the N1P1 amplitude and to determine the factors that impact the outcome. Measurements were performed on 32 CI patients with either CI24RE (CA) or CI512 implants using the Software Custom Sound EP (Cochlear). N1P1 error approximation of non-averaged raw data consisting of recorded single-sweeps was compared to methods of error approximation based on mean curves. The error approximation of the N1P1 amplitude using averaged data showed comparable results to single-point error estimation. The error of the N1P1 amplitude depends on the number of averaging steps and amplification; in contrast, the error of the N1P1 amplitude is not dependent on the stimulus intensity. Single-point error showed smaller N1P1 error and better coincidence with 1/√(N) function (N is the number of measured sweeps) compared to the known maximum-minimum criterion. Evaluation of N1P1 amplitude should be accompanied by indication of its error. The retrospective approximation of this measurement error from the averaged data available in clinically used software is possible and best done utilizing the D-trace in forward masking artefact reduction mode (no stimulation applied and recording contains only the switch-on-artefact). Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Can Treadmill Perturbations Evoke Stretch Reflexes in the Calf Muscles?

    Directory of Open Access Journals (Sweden)

    Lizeth H Sloot

    Full Text Available Disinhibition of reflexes is a problem amongst spastic patients, for it limits a smooth and efficient execution of motor functions during gait. Treadmill belt accelerations may potentially be used to measure reflexes during walking, i.e. by dorsal flexing the ankle and stretching the calf muscles, while decelerations show the modulation of reflexes during a reduction of sensory feedback. The aim of the current study was to examine if belt accelerations and decelerations of different intensities applied during the stance phase of treadmill walking can evoke reflexes in the gastrocnemius, soleus and tibialis anterior in healthy subjects. Muscle electromyography and joint kinematics were measured in 10 subjects. To determine whether stretch reflexes occurred, we assessed modelled musculo-tendon length and stretch velocity, the amount of muscle activity, as well as the incidence of bursts or depressions in muscle activity with their time delays, and co-contraction between agonist and antagonist muscle. Although the effect on the ankle angle was small with 2.8±1.0°, the perturbations caused clear changes in muscle length and stretch velocity relative to unperturbed walking. Stretched muscles showed an increasing incidence of bursts in muscle activity, which occurred after a reasonable electrophysiological time delay (163-191 ms. Their amplitude was related to the muscle stretch velocity and not related to co-contraction of the antagonist muscle. These effects increased with perturbation intensity. Shortened muscles showed opposite effects, with a depression in muscle activity of the calf muscles. The perturbations only slightly affected the spatio-temporal parameters, indicating that normal walking was retained. Thus, our findings showed that treadmill perturbations can evoke reflexes in the calf muscles and tibialis anterior. This comprehensive study could form the basis for clinical implementation of treadmill perturbations to functionally

  12. Central phencyclidine (PCP) receptor binding is glutamate dependent: evidence for a PCP/excitatory amino acid receptor (EAAR) complex

    Energy Technology Data Exchange (ETDEWEB)

    Loo, P.; Braunwalder, A.; Lehmann, J.; Williams, M.

    1986-03-01

    PCP and other dissociative anesthetica block the increase in neuronal firing rate evoked by the EAAR agonist, N-methyl-Daspartate. NMDA and other EAAs such as glutamate (glu) have not been previously shown to affect PCP ligand binding. In the present study, using once washed rat forebrain membranes, 10 ..mu..M-glu was found to increase the binding of (/sup 3/H)TCP, a PCP analog, to defined PCP recognition sites by 20%. Removal of glu and aspartate (asp) by extensive washing decreased TCP binding by 75-90%. In these membranes, 10 ..mu..M L-glu increased TCP binding 3-fold. This effect was stereospecific and evoked by other EAAs with the order of activity, L-glu > D-asp > L- asp > NMDA > D-glu > quisqualate. Kainate, GABA, NE, DA, 5-HT, 2-chloroadenosine, oxotremorine and histamine had no effect on TCP binding at concentrations up to 100 ..mu..M. The effects of L-glu were attenuated by the NMDA-type receptor antagonist, 2-amino-7--phosphonoheptanoate (AP7; 10 ..mu..M-1 mM). These findings indicate that EAAS facilitate TCP binding, possibly through NMDA-type receptors. The observed interaction between the PCP receptor and EAARs may reflect the existence of a macromolecular receptor complex similar to that demonstrated for the benzodiazepines and GABA.

  13. Painful Intercourse Is Significantly Associated with Evoked Pain Perception and Cognitive Aspects of Pain in Women with Pelvic Pain

    Science.gov (United States)

    Alappattu, Meryl J; George, Steven Z; Robinson, Michael E; Fillingim, Roger B; Moawad, Nashat; LeBrun, Emily Weber; Bishop, Mark D

    2015-01-01

    Introduction Evidence suggests that painful intercourse, pain-related psychosocial factors, and altered pain processing magnify the pain experience, but it is not clear how these factors are related to each other. Aim The aims were to (i) characterize differences between women with pelvic pain and pain-free women using a battery of pain-related psychosocial measures, clinical pain ratings, and evoked local and remote pain sensitivity; and (ii) examine the relationship between intercourse pain, clinical pain, and local and remote evoked pain sensitivity. Methods Women with pelvic pain lasting at least 3 months and pain-free women completed questionnaires and underwent pain sensitivity testing. Self-report measures included clinical pain intensity, pain catastrophizing, pain-related fear, pain anxiety, depression, sexual function, and self-efficacy. Pain sensitivity measures included threshold and tolerance and temporal summation of pain. Separate analyses of variance (anova) were used to test group differences in self-report and pain sensitivity measures. Correlations were calculated among dyspareunia, psychosocial factors, and evoked pain. Main Outcome Measures Self-reported pain and pain sensitivity measures. Results Twenty-eight pain-free women and 14 women with pelvic pain participated in this study. Women with pelvic pain reported greater pain intensity and greater psychosocial involvement compared with pain-free women. No differences existed between groups for thermal or pressure measures, but women with pelvic pain rated their pain with pain testing significantly higher than pain-free women. Intercourse pain was significantly associated with affective and sensory pain and pressure pain ratings at the puborectalis, vulvar vestibule, adductor longus tendons, and tibialis anterior muscle. Conclusions Differences in local pain ratings suggest that women with pelvic pain perceive stimuli in this region as more painful than pain-free women although the magnitude of

  14. Distributions of Irritative Zones Are Related to Individual Alterations of Resting-State Networks in Focal Epilepsy.

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    Yinchen Song

    Full Text Available Alterations in the connectivity patterns of the fMRI-based resting-state networks (RSNs have been reported in several types of epilepsies. Evidence pointed out these alterations might be associated with the genesis and propagation of interictal epileptiform discharges (IEDs. IEDs also evoke blood-oxygen-level dependent (BOLD responses, which have been used to delineate irritative zones during preoperative work-up. Therefore, one may expect a relationship between the topology of the IED-evoked BOLD response network and the altered spatial patterns of the RSNs. In this study, we used EEG recordings and fMRI data obtained simultaneously from a chronic model of focal epilepsy in Wistar rats to verify our hypothesis. We found that IED-evoked BOLD response networks comprise both cortical and subcortical structures with a rat-dependent topology. In all rats, IEDs evoke both activation and deactivation types of BOLD responses. Using a Granger causality method, we found that in many cases areas with BOLD deactivation have directed influences on areas with activation (p<0.05. We were able to predict topological properties (i.e., focal/diffused, unilateral/bilateral of the IED-evoked BOLD response network by performing hierarchical clustering analysis on major spatial features of the RSNs. All these results suggest that IEDs and disruptions in the RSNs found previously in humans may be different manifestations of the same transient events, probably reflecting altered consciousness. In our opinion, the shutdown of specific nodes of the default mode network may cause uncontrollable excitability in other functionally connected brain areas. We conclude that IED-evoked BOLD responses (i.e., activation and deactivation and alterations of RSNs are intrinsically related, and speculate that an understanding of their interplay is necessary to discriminate focal epileptogenesis and network propagation phenomena across different brain modules via hub

  15. Distributions of Irritative Zones Are Related to Individual Alterations of Resting-State Networks in Focal Epilepsy

    Science.gov (United States)

    Song, Yinchen; Sanganahalli, Basavaraju G.; Hyder, Fahmeed; Lin, Wei-Chiang; Riera, Jorge J.

    2015-01-01

    Alterations in the connectivity patterns of the fMRI-based resting-state networks (RSNs) have been reported in several types of epilepsies. Evidence pointed out these alterations might be associated with the genesis and propagation of interictal epileptiform discharges (IEDs). IEDs also evoke blood-oxygen-level dependent (BOLD) responses, which have been used to delineate irritative zones during preoperative work-up. Therefore, one may expect a relationship between the topology of the IED-evoked BOLD response network and the altered spatial patterns of the RSNs. In this study, we used EEG recordings and fMRI data obtained simultaneously from a chronic model of focal epilepsy in Wistar rats to verify our hypothesis. We found that IED-evoked BOLD response networks comprise both cortical and subcortical structures with a rat-dependent topology. In all rats, IEDs evoke both activation and deactivation types of BOLD responses. Using a Granger causality method, we found that in many cases areas with BOLD deactivation have directed influences on areas with activation (p<0.05). We were able to predict topological properties (i.e., focal/diffused, unilateral/bilateral) of the IED-evoked BOLD response network by performing hierarchical clustering analysis on major spatial features of the RSNs. All these results suggest that IEDs and disruptions in the RSNs found previously in humans may be different manifestations of the same transient events, probably reflecting altered consciousness. In our opinion, the shutdown of specific nodes of the default mode network may cause uncontrollable excitability in other functionally connected brain areas. We conclude that IED-evoked BOLD responses (i.e., activation and deactivation) and alterations of RSNs are intrinsically related, and speculate that an understanding of their interplay is necessary to discriminate focal epileptogenesis and network propagation phenomena across different brain modules via hub-based connectivity. PMID

  16. Fasting Activation of AgRP Neurons Requires NMDA Receptors and Involves Spinogenesis and Increased Excitatory Tone

    Science.gov (United States)

    Liu, Tiemin; Kong, Dong; Shah, Bhavik P.; Ye, Chianping; Koda, Shuichi; Saunders, Arpiar; Ding, Jun B.; Yang, Zongfang; Sabatini, Bernardo L.; Lowell, Bradford B.

    2012-01-01

    SUMMARY AgRP neuron activity drives feeding and weight gain while that of nearby POMC neurons does the opposite. However, the role of excitatory glutamatergic input in controlling these neurons is unknown. To address this question, we generated mice lacking NMDA receptors (NMDARs) on either AgRP or POMC neurons. Deletion of NMDARs from AgRP neurons markedly reduced weight, body fat and food intake whereas deletion from POMC neurons had no effect. Activation of AgRP neurons by fasting, as assessed by c-Fos, Agrp and Npy mRNA expression, AMPA receptor-mediated EPSCs, depolarization and firing rates, required NMDARs. Furthermore, AgRP but not POMC neurons have dendritic spines and increased glutamatergic input onto AgRP neurons caused by fasting was paralleled by an increase in spines, suggesting fasting induced synaptogenesis and spinogenesis. Thus glutamatergic synaptic transmission and its modulation by NMDARs play key roles in controlling AgRP neurons and determining the cellular and behavioral response to fasting. PMID:22325203

  17. Imbalance between excitatory and inhibitory amino acids at spinal level is associated with maintenance of persistent pain-related behaviors.

    Science.gov (United States)

    Yan, Lai-Hong; Hou, Jun-Feng; Liu, Ming-Gang; Li, Meng-Meng; Cui, Xiu-Yu; Lu, Zhuo-Min; Zhang, Fu-Kang; An, Yang-Yuan; Shi, Lin; Chen, Jun

    2009-05-01

    Although the postsynaptic events responsible for development of pathological pain have been intensively studied, the relative contribution of presynaptic neurotransmitters to the whole process remains less elucidated. In the present investigation, we sought to measure temporal changes in spinal release of both excitatory amino acids (EAAs, glutamate and aspartate) and inhibitory amino acids (IAAs, glycine, ?-aminobutyric acid and taurine) in response to peripheral inflammatory pain state. The results showed that following peripheral chemical insult induced by subcutaneous bee venom (BV) injection, there was an initial, parallel increase in spinal release of both EAAs and IAAs, however, the balance between them was gradually disrupted when pain persisted longer, with EAAs remaining at higher level but IAAs at a level below the baseline. Moreover, the EAAs-IAAs imbalance at the spinal level was dependent upon the ongoing activity from the peripheral injury site. Intrathecal blockade of ionotropic (NMDA and non-NMDA) and metabotropic (mGluRI, II, III) glutamate receptors, respectively, resulted in a differential inhibition of BV-induced different types of pain (persistent nociception vs. hyperalgesia, or thermal vs. mechanical hyperalgesia), implicating that spinal antagonism of any specific glutamate receptor subtype fails to block all types of pain-related behaviors. This result provides a new line of evidence emphasizing an importance of restoration of EAAs-IAAs balance at the spinal level to prevent persistence or chronicity of pain.

  18. Marked Elevation of Excitatory Amino Acids in Cerebrospinal Fluid Obtained From Patients With Rotavirus-Associated Encephalopathy.

    Science.gov (United States)

    Kashiwagi, Yasuyo; Kawashima, Hisashi; Suzuki, Shunsuke; Nishimata, Shigeo; Takekuma, Koji; Hoshika, Akinori

    2015-07-01

    Rotavirus is the most common cause of severe gastroenteritis in young children; however, its pathogenesis and immunity are not completely understood. Even less well recognized is rotavirus-induced central nervous system (CNS) involvement, which has been associated with seizure, encephalopathy and death, among others. To elucidate the host response to rotavirus infection, we retrospectively examined neurotransmitter amino acids in the cerebrospinal fluid (CSF) of 19 children with CNS involvement associated with rotavirus infection. Subjects were classified into two groups: those with encephalopathy followed by prolonged seizure (encephalopathy group) and those who had experienced afebrile, brief cluster of seizures without encephalopathy (cluster group). The levels of glutamate, glycine, and taurine in the encephalopathy group were significantly higher than those in the cluster group. Increased levels of excitatory amino acids in the CSF may induce neurological disorders and be related to disorder severity. To the best of our knowledge, this is the first report regarding amino acids in the CSF obtained from patients with rotavirus-induced CNS involvement. Further study is necessary to elucidate the role of CSF amino acid levels in rotavirus-induced CNS involvement. © 2014 Wiley Periodicals, Inc.

  19. Physiological and chemical analysis of neurotransmitter candidates at a fast excitatory synapse in the jellyfish Cyanea capillata (Cnidaria, Scyphozoa).

    Science.gov (United States)

    Anderson, Peter A V; Trapido-Rosenthal, H G

    2009-12-01

    Motor nerve net (MNN) neurons in the jellyfish Cyanea capillata communicate with one another by way of fast, bidirectional excitatory chemical synapses. As is the case with almost all identified chemical synapses in cnidarians, the identity of the neurotransmitter at these synapses is unclear. MNN neurons are large enough for stable intracellular recordings. This, together with the fact that they can be exposed, providing unlimited access to them and to their synapses, prompted a study of the action of a variety of neurotransmitter candidates, including those typically associated with fast synapses in higher animals. Only the amino acids taurine and beta-alanine produced physiological responses consistent with those of the normal EPSP in these cells. Moreover, chemical analysis revealed that both taurine and beta-alanine are present in the neurons and released by depolarization. These various findings strongly suggest that either or both of these amino acids, or a closely related compound is the neurotransmitter at the fast chemical synapses between MNN neurons.

  20. Effects of Hebbian learning on the dynamics and structure of random networks with inhibitory and excitatory neurons.

    Science.gov (United States)

    Siri, Benoît; Quoy, Mathias; Delord, Bruno; Cessac, Bruno; Berry, Hugues

    2007-01-01

    The aim of the present paper is to study the effects of Hebbian learning in random recurrent neural networks with biological connectivity, i.e. sparse connections and separate populations of excitatory and inhibitory neurons. We furthermore consider that the neuron dynamics may occur at a (shorter) time scale than synaptic plasticity and consider the possibility of learning rules with passive forgetting. We show that the application of such Hebbian learning leads to drastic changes in the network dynamics and structure. In particular, the learning rule contracts the norm of the weight matrix and yields a rapid decay of the dynamics complexity and entropy. In other words, the network is rewired by Hebbian learning into a new synaptic structure that emerges with learning on the basis of the correlations that progressively build up between neurons. We also observe that, within this emerging structure, the strongest synapses organize as a small-world network. The second effect of the decay of the weight matrix spectral radius consists in a rapid contraction of the spectral radius of the Jacobian matrix. This drives the system through the "edge of chaos" where sensitivity to the input pattern is maximal. Taken together, this scenario is remarkably predicted by theoretical arguments derived from dynamical systems and graph theory.

  1. An Investigation of the Late Excitatory Potentials in the Hand following Transcranial Magnetic Stimulation in Early Alzheimer's Disease

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    Christina Balla

    2014-11-01

    Full Text Available Background: Recent neuroimaging studies in humans support the clinical observations that the motor cortex is affected early in the course of Alzheimer's disease (AD. Patients and Methods: We measured the silent period (SP induced by transcranial magnetic stimulation in AD patients in the very early stage of the disease, and we explored whether and in which way the pharmacologic manipulation of the cholinergic system could modify it. Results: An increase in the duration of the SP was observed in AD patients in the early stage in comparison to controls. After 2 months of treatment with donepezil, the duration did not differ significantly from that of normal subjects. The results of our study show a fragmentation and an enlargement of the SP in the presence of multiple late excitatory potentials (LEPs in early untreated AD patients. These LEPs were also modulated by donepezil. Conclusions: The results suggest an early functional impairment of cholinergic neurotransmission in AD. The disturbance in acetylcholine output in early AD leads to a decrease in excitability of the motor system.

  2. 9-Phenanthrol modulates postinhibitory rebound and afterhyperpolarizing potentials in an excitatory motor neuron of the medicinal leech.

    Science.gov (United States)

    Angstadt, James D; Giordano, Joshua R; Goncalves, Alexander J

    2017-08-01

    Postinhibitory rebound (PIR) responses in leech dorsal excitatory motor neurons (cell DE-3) are eliminated by Ca2+ channel blockers but also exhibit a strong dependence on extracellular Na+. These features could be explained by a voltage-gated Ca2+ current acting in concert with a Ca2+-activated nonspecific current (ICAN). In vertebrates, ICAN is associated with TRPM4 channels which are blocked selectively by 9-phenanthrol. Here, we show that 9-phenanthrol selectively inhibits a late phase of PIR and simultaneously enhances afterhyperpolarizing potentials (AHPs). Bath application of NNC 55-0396 or Cd2+ combined with ion substitution experiments indicate that a low-voltage-activated Ca2+ current plays a key role in generating PIR and that Ca2+ influx through low- or high-voltage-activated Ca2+ channels can trigger AHPs via activation of a Ca2+-dependent K+ current. We also demonstrate modulation of rebound responses by other ICAN blockers such as gadolinium and flufenamic acid, as well as the calmodulin antagonist W-7. We discuss how these results provide additional insights into the specific types of ionic currents underlying rebound responses of motor neuron DE-3 in the medicinal leech.

  3. 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.

  4. How Do RIM-BPs Link Voltage-Gated Ca(2+) Channels to Evoked Neurotransmitter Release?

    Science.gov (United States)

    Li, Ying C; Kavalali, Ege T

    2015-09-23

    Coupling between voltage-gated Ca(2+) influx and synaptic vesicle exocytosis is essential for rapid evoked neurotransmission. Acuna et al. show that the knockout of RIM-BPs, which are key structural components of this coupling, decreases the reliability of evoked neurotransmitter release. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Sex and Ear Differences in Spontaneous and Click-Evoked Otoacoustic Emissions in Young Adults

    Science.gov (United States)

    Snihur, Adrian W. K.; Hampson, Elizabeth

    2011-01-01

    Effects of sex and handedness on the production of spontaneous and click-evoked otoacoustic emissions (OAEs) were explored in a non-hearing impaired population (ages 17-25 years). A sex difference in OAEs, either produced spontaneously (spontaneous OAEs or SOAEs) or in response to auditory stimuli (click-evoked OAEs or CEOAEs) has been reported in…

  6. The Nature and Process of Development in Averaged Visually Evoked Potentials: Discussion on Pattern Structure.

    Science.gov (United States)

    Izawa, Shuji; Mizutani, Tohru

    This paper examines the development of visually evoked EEG patterns in retarded and normal subjects. The paper focuses on the averaged visually evoked potentials (AVEP) in the central and occipital regions of the brain in eyes closed and eyes open conditions. Wave pattern, amplitude, and latency are examined. The first section of the paper reviews…

  7. One Year of Musical Training Affects Development of Auditory Cortical-Evoked Fields in Young Children

    Science.gov (United States)

    Fujioka, Takako; Ross, Bernhard; Kakigi, Ryusuke; Pantev, Christo; Trainor, Laurel J.

    2006-01-01

    Auditory evoked responses to a violin tone and a noise-burst stimulus were recorded from 4- to 6-year-old children in four repeated measurements over a 1-year period using magnetoencephalography (MEG). Half of the subjects participated in musical lessons throughout the year; the other half had no music lessons. Auditory evoked magnetic fields…

  8. Long-term visuo-gustatory appetitive and aversive conditioning potentiate human visual evoked potentials

    DEFF Research Database (Denmark)

    Christoffersen, Gert R.J.; Laugesen, Jakob L.; Møller, Per

    2017-01-01

    and aversive visuo-gustatory conditioning were studied with high density EEG-recordings focusing on late components in the visual evoked potentials (VEPs), specifically the N2-P3 waves. Unfamiliar images were paired with either a pleasant or an unpleasant juice and VEPs evoked by the images were compared...

  9. The effect of changes in perilymphatic K+ on the vestibular evoked potential in the guinea pig

    NARCIS (Netherlands)

    Kingma, C. M.; Wit, H. P.

    2010-01-01

    To investigate the effect on the functioning of the vestibular system of a rupture of Reissner's membrane, artificial endolymph was injected in scala media of ten guinea pigs and vestibular evoked potentials (VsEPs), evoked by vertical acceleration pulses, were measured. Directly after injection of

  10. 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

  11. Long-Term Visuo-Gustatory Appetitive and Aversive Conditioning Potentiate Human Visual Evoked Potentials

    DEFF Research Database (Denmark)

    Christoffersen, Gert Rene Juul; Laugesen, Jakob Lund; Møller, Per

    2017-01-01

    and aversive visuo-gustatory conditioning were studied with high density EEG-recordings focusing on late components in the visual evoked potentials (VEPs), specifically the N2-P3 waves. Unfamiliar images were paired with either a pleasant or an unpleasant juice and VEPs evoked by the images were compared...

  12. 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.

  13. Dorsal root activity evoked by stimulation of vagina-cervix-uterus junction in the rat.

    Science.gov (United States)

    Tovar, Anibal; Lara-Garcia, Miguel; Cruz, Yolanda; Pacheco, Pablo

    2013-02-16

    In the present study, we characterized the evoked electrical activity from T(13) to S(2) dorsal roots (DRs) during glass probe-stimulation of the vagina-cervix-uterus junction (VCUJ) of female Wistar rats. The results showed that gentle stimulation of VCUJ evoked high-amplitude electrical activity in L(3) and L(6) DRs. Hypogastric or pelvic nerve transection failed to abolish this activity. L(6)-S(1) spinal trunk transection abolished the high-amplitude electrical activity evoked in L(6) DR, while transection of the lumbosacral trunk blocked the high-amplitude electrical activity evoked in L(3) DR. These data suggest that during copulation, penile intromission likely activates the low-threshold sensory receptors of the VCUJ, thereby evoking sensory neural activity that enters the spinal cord via L(3) and L(6) dorsal roots, whose axons travel through the lumbosacral trunk and pudendal nerve. Copyright © 2013. Published by Elsevier B.V.

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

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    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.

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

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    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.

  16. Differential effects of prenatal chronic high-decibel noise and music exposure on the excitatory and inhibitory synaptic components of the auditory cortex analog in developing chicks (Gallus gallus domesticus).

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    Kumar, V; Nag, T C; Sharma, U; Jagannathan, N R; Wadhwa, S

    2014-06-06

    Proper development of the auditory cortex depends on early acoustic experience that modulates the balance between excitatory and inhibitory (E/I) circuits. In the present social and occupational environment exposure to chronic loud sound in the form of occupational or recreational noise, is becoming inevitable. This could especially disrupt the functional auditory cortex development leading to altered processing of complex sound and hearing impairment. Here we report the effects of prenatal chronic loud sound (110-dB sound pressure level (SPL)) exposure (rhythmic [music] and arrhythmic [noise] forms) on the molecular components involved in regulation of the E/I balance in the developing auditory cortex analog/Field L (AuL) in domestic chicks. Noise exposure at 110-dB SPL significantly enhanced the E/I ratio (increased expression of AMPA receptor GluR2 subunit and glutamate with decreased expression of GABA(A) receptor gamma 2 subunit and GABA), whereas loud music exposure maintained the E/I ratio. Expressions of markers of synaptogenesis, synaptic stability and plasticity i.e., synaptophysin, PSD-95 and gephyrin were reduced with noise but increased with music exposure. Thus our results showed differential effects of prenatal chronic loud noise and music exposures on the E/I balance and synaptic function and stability in the developing auditory cortex. Loud music exposure showed an overall enrichment effect whereas loud noise-induced significant alterations in E/I balance could later impact the auditory function and associated cognitive behavior. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. Genetic rescue of CB1 receptors on medium spiny neurons prevents loss of excitatory striatal synapses but not motor impairment in HD mice.

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    Naydenov, Alipi V; Sepers, Marja D; Swinney, Katie; Raymond, Lynn A; Palmiter, Richard D; Stella, Nephi

    2014-11-01

    Huntington's disease (HD) is caused by an expanded polyglutamine repeat in huntingtin protein that disrupts synaptic function in specific neuronal populations and results in characteristic motor, cognitive and affective deficits. Histopathological hallmarks observed in both HD patients and genetic mouse models include the reduced expression of synaptic proteins, reduced medium spiny neuron (MSN) dendritic spine density and decreased frequency of spontaneous excitatory post-synaptic currents (sEPSCs). Early down-regulation of cannabinoid CB1 receptor expression on MSN (CB1(MSN)) is thought to participate in HD pathogenesis. Here we present a cell-specific genetic rescue of CB1(MSN) in R6/2 mice and report that treatment prevents the reduction of excitatory synaptic markers in the striatum (synaptophysin, vGLUT1 and vGLUT2), of dendritic spine density on MSNs and of MSN sEPSCs, but does not prevent motor impairment. We conclude that loss of excitatory striatal synapses in HD mice is controlled by CB1(MSN) and can be uncoupled from the motor phenotype. Copyright © 2014 Elsevier Inc. All rights reserved.

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

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    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.

  19. Mechanism of ceftriaxone induction of excitatory amino acid transporter-2 expression and glutamate uptake in primary human astrocytes.

    Science.gov (United States)

    Lee, Seok-Geun; Su, Zhao-Zhong; Emdad, Luni; Gupta, Pankaj; Sarkar, Devanand; Borjabad, Alejandra; Volsky, David J; Fisher, Paul B

    2008-05-09

    Glutamate is an essential neurotransmitter regulating brain functions. Excitatory amino acid transporter (EAAT)-2 is one of the major glutamate transporters primarily expressed in astroglial cells. Dysfunction of EAAT2 is implicated in acute and chronic neurological disorders, including stroke/ischemia, temporal lobe epilepsy, amyotrophic lateral sclerosis, Alzheimer disease, human immunodeficiency virus 1-associated dementia, and growth of malignant gliomas. Ceftriaxone, one of the beta-lactam antibiotics, is a stimulator of EAAT2 expression with neuroprotective effects in both in vitro and in vivo models based in part on its ability to inhibit neuronal cell death by glutamate excitotoxicity. Based on this consideration and its lack of toxicity, ceftriaxone has potential to manipulate glutamate transmission and ameliorate neurotoxicity. We investigated the mechanism by which ceftriaxone enhances EAAT2 expression in primary human fetal astrocytes (PHFA). Ceftriaxone elevated EAAT2 transcription in PHFA through the nuclear factor-kappaB (NF-kappaB) signaling pathway. The antibiotic promoted nuclear translocation of p65 and activation of NF-kappaB. The specific NF-kappaB binding site at the -272 position of the EAAT2 promoter was responsible for ceftriaxone-mediated EAAT2 induction. In addition, ceftriaxone increased glutamate uptake, a primary function of EAAT2, and EAAT2 small interference RNA completely inhibited ceftriaxone-induced glutamate uptake activity in PHFA. Taken together, our data indicate that ceftriaxone is a potent modulator of glutamate transport in PHFA through NF-kappaB-mediated EAAT2 promoter activation. These findings suggest a mechanism for ceftriaxone modulation of glutamate transport and for its potential effects on ameliorating specific neurodegenerative diseases through modulation of extracellular glutamate.

  20. Non-excitatory electrical stimulation attenuates myocardial infarction via homeostasis of calcitonin gene-related peptide in myocardium.

    Science.gov (United States)

    Guo, Zhi-Jia; Guo, Zheng

    2015-03-01

    Electrical stimulation has been shown protection of brain, retina, optic nerves and pancreatic β-cells but the effect on cardio-protection is still unknown. Calcitonin gene-related peptide (CGRP) participates in the pathology of injury and protection of myocardium but whether or not electrical stimulation modulates endogenous CGRP is not clear. Male Sprague-Dawley rats were divided into 4 groups: (1) control group, without any treatment. (2) I/R group, animals were subjected to 30 min of myocardial ischemia followed by 60 min reperfusion. (3) NES+I/R group, non-excitatory electrical stimulation (NES) was commenced from 15 min before coronary artery occlusion till the end of reperfusion. (4) I/R+CGRP8-37 group, animals were given with CGRP8-37 (an antagonist of CGRP receptor, 10(-7) mol/L, 0.3 ml, i.v.) at 5 min before reperfusion without any electrical stimulation. The hemodynamics and electrocardiogram were monitored and recorded. Infarct size and troponin I were examined and CGRP expression in the myocardium and serum was analyzed. It was found that the infarct size and TnI were significantly reduced in NES+I/R group, by 45% and 58% respectively, accompanied by an obvious fall back of CGRP in myocardium, compared to I/R group (all pTreatment with CGRP8-37 resulted in the same protection on myocardium as NES did. No significant difference in hemodynamics or ventricular tachycardia was detected among the groups (all p>0.05). It can be concluded that NES reduced the infarction size after acute myocardial ischemia and reperfusion, for which the underlying mechanism may be associated with modulation of endogenous CGRP in myocardium. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Simultaneously Excitatory and Inhibitory Effects of Transcranial Alternating Current Stimulation Revealed Using Selective Pulse-Train Stimulation in the Rat Motor Cortex.

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    Khatoun, Ahmad; Asamoah, Boateng; Mc Laughlin, Myles

    2017-09-27

    Transcranial alternating current stimulation (tACS) uses sinusoidal, subthreshold, electric fields to modulate cortical processing. Cortical processing depends on a fine balance between excitation and inhibition and tACS acts on both excitatory and inhibitory cortical neurons. Given this, it is not clear whether tACS should increase or decrease cortical excitability. We investigated this using transcranial current stimulation of the rat (all males) motor cortex consisting of a continuous subthreshold sine wave with short bursts of suprathreshold pulse-trains inserted at different phases to probe cortical excitability. We found that when a low-rate, long-duration, suprathreshold pulse-train was used, subthreshold cathodal tACS decreased cortical excitability and anodal tACS increased excitability. However, when a high-rate, short-duration, suprathreshold pulse-train was used this pattern was inverted. An integrate-and-fire model incorporating biophysical differences between cortical excitatory and inhibitory neurons could predict the experimental data and helped interpret these results. The model indicated that low-rate suprathreshold pulse-trains preferentially stimulate excitatory cortical neurons, whereas high-rate suprathreshold pulse-trains stimulate both excitatory and inhibitory neurons. If correct, this indicates that suprathreshold pulse-train stimulation may be able to selectively control the excitation-inhibition balance within a cortical network. The excitation-inhibition balance then likely plays an important role in determining whether subthreshold tACS will increase or decrease cortical excitability.SIGNIFICANCE STATEMENT Transcranial alternating current stimulation (tACS) is a noninvasive neuromodulation method that uses weak sinusoidal electric fields to modulate cortical activity. In healthy volunteers tACS can modulate perception, cognition, and motor function but the underlying neural mechanism is poorly understood. In this study, using rat motor

  2. Stimulus-Evoked Electromyographic Monitoring During Minimally Invasive Transpedicular Implantation of Screws in Lumbosacral Spine: Threshold Value, Methodology and Clinical Effectiveness.

    Science.gov (United States)

    Wu, Yunfen; Vázquez-Barquero, Alfonso

    2017-02-01

    Stimulus-evoked electromyography (EMG) has been developed to increase the safety of transpedicular placement of screws. There is more consensus about this monitoring method in open surgery. Alarm thresholds for minimally invasive surgery are based on referential value for open surgery. Nevertheless, there are no uniform alarm criteria on this modality for minimally invasive surgery. Using an analysis of alarm threshold, methodology and clinical effectiveness on stimulus-evoked EMG monitoring for minimally invasive transpedicular implantation of screws in the lumbosacral spine, this study aims to reflect and recommend for optimizing accuracy. Using a selection of studies, an analysis of the pedicle breach rates and breach-related clinical complication rates was made between studies on minimally invasive surgery by applying different thresholds. A second analysis of the pedicle breach rates and breach-related clinical complication rates was made between studies on open and minimally invasive surgery by applying the same threshold. In minimally invasive surgery, stimulus-evoked EMG has an acceptable accuracy in the detection of clinical relevant pedicle breaches. Suction limitation may alter the stimulation threshold. No significant differences in clinical effectiveness were observed between studies by applying thresholds of 5 mA, 7 mA, and 12 mA. However, a low threshold of 5 mA seems inappropriate for the tap stimulation. In minimally invasive surgery, continuous stimulation of instrumentation devices is recommended. A minimum 5-mA threshold should be used for stimulation of the pedicle access needle. Use of higher-stimulation thresholds during tapping and incorporation of an adapted continuous suction system may optimize the accuracy of stimulus-evoked EMG. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Transient Evoked and Distortion Product Otoacoustic Emissions in a Group of Neonates

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    Silva, Giovanna Cesar; Delecrode, Camila Ribas; Kemp, Adriana Tahara; Martins, Fabiana; Cardoso, Ana Claudia Vieira

    2015-01-01

    Introduction The most commonly used method in neonatal hearing screening programs is transient evoked otoacoustic emissions in the first stage of the process. There are few studies comparing transient evoked otoacoustic emissions with distortion product, but some authors have investigated the issue. Objective To correlate the results of transient evoked and distortion product otoacoustic emissions in a Brazilian maternity hospital. Methods This is a cross-sectional, comparative, and prospective study. The study included 579 newborns, ranging from 6 to 54 days of age, born in a low-risk maternity hospital and assessed for hearing loss. All neonates underwent hearing screening by transient evoked and distortion product otoacoustic emissions. The results were analyzed using the Spearman correlation test to relate the two procedures. Results The pass index on transient evoked otoacoustic emissions was 95% and on distortion product otoacoustic emissions was 91%. The comparison of the two procedures showed that 91% of neonates passed on both procedures, 4.5% passed only on transient evoked otoacoustic emissions, 0.5% passed only on distortion product otoacoustic emissions, and 4% failed on both procedures. The inferential analysis showed a significant strong positive relationship between the two procedures. Conclusion The failure rate was higher in distortion product otoacoustic emissions when compared with transient evoked; however, there was correlation between the results of the procedures. PMID:26157501

  4. Language impairment is reflected in auditory evoked fields.

    Science.gov (United States)

    Pihko, Elina; Kujala, Teija; Mickos, Annika; Alku, Paavo; Byring, Roger; Korkman, Marit

    2008-05-01

    Specific language impairment (SLI) is diagnosed when a child has problems in producing or understanding language despite having a normal IQ and there being no other obvious explanation. There can be several associated problems, and no single underlying cause has yet been identified. Some theories propose problems in auditory processing, specifically in the discrimination of sound frequency or rapid temporal frequency changes. We compared automatic cortical speech-sound processing and discrimination between a group of children with SLI and control children with normal language development (mean age: 6.6 years; range: 5-7 years). We measured auditory evoked magnetic fields using two sets of CV syllables, one with a changing consonant /da/ba/ga/ and another one with a changing vowel /su/so/sy/ in an oddball paradigm. The P1m responses for onsets of repetitive stimuli were weaker in the SLI group whereas no significant group differences were found in the mismatch responses. The results indicate that the SLI group, having weaker responses to the onsets of sounds, might have slightly depressed sensory encoding.

  5. Evoking Baldwin’s Blues: The Experience of Dislocated Listening

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    Rashida K. Braggs

    2015-09-01

    Full Text Available “It is only in his music [. . .] that the Negro in America has been able to tell his story. It is a story which otherwise has yet to be told and which no American is prepared to hear,” so wrote James Baldwin in “Many Thousands Gone.” Throughout his career, James Baldwin returned to this incomprehension of African-American experience. He continually privileged music in his literature, crafting his own literary blues to address it. Baldwin’s blues resonated even more powerfully and painfully for its emotional and geographical dislocation. In this article, Rashida K. Braggs argues that it was the combination of music, word, and migration that prompted Baldwin’s own deeper understanding. Exploring her term dislocated listening, Braggs investigates how listening to music while willfully dislocated from one’s cultural home prompts a deeper understanding of African-American experience. The distance disconcerts, leaving one more vulnerable, while music impels the reader, audience, and even Baldwin to identify with some harsh realities of African-American experience. Baldwin evokes the experience of dislocated listening in his life and in “Sonny’s Blues.” Braggs also creates an experience of dislocated listening through her video performance of Baldwin’s words, thus attempting to draw the reader as well into a more attuned understanding of African-American experience.

  6. Brain stem evoked response audiometry of former drug users.

    Science.gov (United States)

    Weich, Tainara Milbradt; Tochetto, Tania Maria; Seligman, Lilian

    2012-10-01

    Illicit drugs are known for their deleterious effects upon the central nervous system and more specifically for how they adversely affect hearing. This study aims to analyze and compare the hearing complaints and the results of brainstem evoked response audiometry (BERA) of former drug user support group goers. This is a cross-sectional non-experimental descriptive quantitative study. The sample consisted of 17 subjects divided by their preferred drug of use. Ten individuals were placed in the marijuana group (G1) and seven in the crack/cocaine group (G2). The subjects were further divided based on how long they had been using drugs: 1 to 5 years, 6 to 10 years, and over 15 years. They were interviewed, and assessed by pure tone audiometry, acoustic impedance tests, and BERA. No statistically significant differences were found between G1 and G2 or time of drug use in absolute latencies and interpeak intervals. However, only five of the 17 individuals had BERA results with adequate results for their ages. Marijuana and crack/cocaine may cause diffuse disorders in the brainstem and compromise the transmission of auditory stimuli regardless of how long these substances are used for.

  7. Analysis of visual evoked responses in multiple sclerosis.

    Science.gov (United States)

    Mallecourt, J; Chain, F; Leblanc, M; Lhermitte, F

    1980-12-01

    In Multiple Sclerosis (MS) the modification of the latency of visual evoked responses (VER's) shows sequels of the involvement of anterior optic tracts manifested by a retro-bulbar optic neuritis (RBON). This study was made on 102 patients with MS. The stimulus used the pattern reversal of a checkboard. The influence of the size and squares 8' and 20' chosen as stimulus has been first studied in patients with antecedents of RBON. Using the 8' squares, all eyes with a history of RBON had pathological VER's. When there is no clinical antecedent of RBON, this means of stimulation enabled us to detect sequels of RBON. In "definitive" and "probable" MS, 100% of patients had pathological VER's either for both eyes of a single eyes. In "possible" MS a sequel of RBON was demonstrated in 57% of this population without clinical antecedent of RBON. A correlation between VER's result and the ophthalmological examination (visual acuity, fundoscopic examination and acquired dyschromatopsie) was made. Although VER's are an excellent method for detecting the sequels of RBON in MS. VER's abnormalities have no etiological significance, they are observed in other neurological involvements of anterior optic tracts. These different points are discussed and a physiological interpretation of VER's abnormalities is proposed.

  8. Neurogenic vestibular evoked potentials using a tone pip auditory stimulus.

    Science.gov (United States)

    Papathanasiou, E S; Zamba-Papanicolaou, E; Pantziaris, M; Kleopas, K; Kyriakides, T; Papacostas, S; Pattichis, C; Iliopoulos, I; Piperidou, C

    2004-01-01

    To obtain neurogenic vestibular evoked potentials (NVESTEPs) with surface scalp recording using a tone pip auditory stimulus. Fourteen neurologically normal volunteers (Age range 26-45 years, 10 females and 4 males), and two patients with sensorineural hearing loss and possible multiple sclerosis respectively, were examined. Two channel recordings were obtained, the first channel being P3 referred to Fpz, and the second channel being P4 referred to Fpz. A 1 kHz tone pip stimulus with two cycles was delivered via headphones monoaurally with contralateral masking noise. A consistent negative wave with a mean absolute latency of 4.72 msec was obtained, which we have named N5. 25% of the ears tested had better responses at the ipsilateral parietal electrode. In the patient with bilateral sensorineural hearing loss, NVESTEPs was present, suggesting that the NVESTEP is not a cochlear response. In the patient with possible multiple sclerosis, an abnormal NVESTEP response and a normal BAEP response were found. Use of a tone-pip rather than a click auditory stimulus allows a lower click intensity to be used in the production of NVESTEP responses, leads to a shorter testing time, and is therefore more comfortable for the patient. This study adds to our impression that the NVESTEP may be a physiological response that can be used to assess the vestibular system and is different from the BAEP response. Further testing in patients with symptoms of dizziness and with disorders specific for the vestibular nerve is required.

  9. A Subspace Method for Dynamical Estimation of Evoked Potentials

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    Stefanos D. Georgiadis

    2007-01-01

    Full Text Available It is a challenge in evoked potential (EP analysis to incorporate prior physiological knowledge for estimation. In this paper, we address the problem of single-channel trial-to-trial EP characteristics estimation. Prior information about phase-locked properties of the EPs is assesed by means of estimated signal subspace and eigenvalue decomposition. Then for those situations that dynamic fluctuations from stimulus-to-stimulus could be expected, prior information can be exploited by means of state-space modeling and recursive Bayesian mean square estimation methods (Kalman filtering and smoothing. We demonstrate that a few dominant eigenvectors of the data correlation matrix are able to model trend-like changes of some component of the EPs, and that Kalman smoother algorithm is to be preferred in terms of better tracking capabilities and mean square error reduction. We also demonstrate the effect of strong artifacts, particularly eye blinks, on the quality of the signal subspace and EP estimates by means of independent component analysis applied as a prepossessing step on the multichannel measurements.

  10. Flash visual evoked potentials in diurnal birds of prey.

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    Dondi, Maurizio; Biaggi, Fabio; Di Ianni, Francesco; Dodi, Pier Luigi; Quintavalla, Fausto

    2016-01-01

    The objective of this pilot study was to evaluate the feasibility of Flash Visual Evoked Potentials (FVEPs) testing in birds of prey in a clinical setting and to describe the protocol and the baseline data for normal vision in this species. FVEP recordings were obtained from 6 normal adult birds of prey: n. 2 Harris's Hawks (Parabuteo unicinctus), n. 1 Lanner Falcon (Falco biarmicus), n. 2 Gyrfalcons (Falco rusticolus) and n. 1 Saker Falcon (Falco cherrug). Before carrying out VEP tests, all animals underwent neurologic and ophthalmic routine examination. Waveforms were analysed to identify reproducible peaks from random variation of baseline. At least three positive and negative peaks were highlighted in all tracks with elevated repeatability. Measurements consisted of the absolute and relative latencies of these peaks (P1, N1, P2, N2, P3, and N3) and their peak-to-peak amplitudes. Both the peak latency and wave morphology achieved from normal animals were similar to those obtained previously in other animal species. This test can be easily and safely performed in a clinical setting in birds of prey and could be useful for an objective assessment of visual function.

  11. Effect of pupil size on multifocal pattern visual evoked potentials.

    Science.gov (United States)

    Martins, Alessandra; Balachandran, Chandra; Klistorner, Alexander I; Graham, Stuart L; Billson, Francis A

    2003-08-01

    The purpose of this study was to investigate the influence of pupil diameter on the amplitude and latency of multifocal visual evoked potentials (mfVEP). The multifocal objective perimeter (Accumap; Objectivision) was used to stimulate the visual field at 56 sites extending to 32 degrees using a pseudo-random pattern stimulus. The mfVEP were recorded using bipolar occipital electrodes, 7 min/eye. Ten normal subjects were recruited from the community and one eye was randomly selected for testing. The mfVEP were recorded at four different pupil diameters (2 mm, 4 mm, 6 mm, 8 mm), obtained by applying tropicamide (0.5%) or pilocarpine (2%) in different dilutions. Appropriate refractive correction was provided to overcome cycloplegia and achieve a visual acuity of 6/7.5 or better. Analysis revealed that at most pupil diameters the normalized full field amplitude did not show significant variation, except at the most miotic pupil diameter (2 mm), where the amplitude became reduced, based on 2-way anova and Tukey's T method. There was, however, significant correlation between latency and pupil area (correlation coefficient: upper field -0.63, lower field -0.76). The results suggest that even in the presence of mydriatics or miotics, the mfVEP test can be used to assess diseases that affect amplitude, provided near correction is used. The interpretation of latency, however, must be made with caution, as a borderline conduction defect with a dilated pupil may appear normal.

  12. Responses evoked by a vestibular implant providing chronic stimulation.

    Science.gov (United States)

    Thompson, Lara A; Haburcakova, Csilla; Gong, Wangsong; Lee, Daniel J; Wall, Conrad; Merfeld, Daniel M; Lewis, Richard F

    2012-01-01

    Patients with bilateral vestibular loss experience dehabilitating visual, perceptual, and postural difficulties, and an implantable vestibular prosthesis that could improve these symptoms would be of great benefit to these patients. In previous work, we have shown that a one-dimensional, unilateral canal prosthesis can improve the vestibulooccular reflex (VOR) in canal-plugged squirrel monkeys. In addition to the VOR, the potential effects of a vestibular prosthesis on more complex, highly integrative behaviors, such as the perception of head orientation and posture have remained unclear. We tested a one-dimensional, unilateral prosthesis in a rhesus monkey with bilateral vestibular loss and found that chronic electrical stimulation partially restored the compensatory VOR and also that percepts of head orientation relative to gravity were improved. However, the one-dimensional prosthetic stimulation had no clear effect on postural stability during quiet stance, but sway evoked by head-turns was modestly reduced. These results suggest that not only can the implementation of a vestibular prosthesis provide partial restitution of VOR but may also improve perception and posture in the presence of bilateral vestibular hypofunction (BVH). In this review, we provide an overview of our previous and current work directed towards the eventual clinical implementation of an implantable vestibular prosthesis.

  13. Protocol to collect late latency auditory evoked potentials.

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    Ventura, Luzia Maria Pozzobom; Alvarenga, Kátia de Freitas; Costa Filho, Orozimbo Alves

    2009-01-01

    Long Latency Auditory Evoked Potentials (LLAEP) represents a number of electrical changes occurring in the central nervous system, resulting from stimulation of the auditory sensorial pathways. Many studies approach the use of these potentials controlling the artifact created by eye movement with the use of equipment with a large number of channels. However, what happens is very different in Brazilian clinical practice, where the equipment used has a very limited number of channels. to compare the two methods used to control the artifacts created by eye movements during LLAEP capture using two recording channels. this is a prospective study with the application of two LLAEP capturing methods (eye artifact subtraction and rejection limit control) in 10 normal hearing individuals. we did not observe statistically significant differences concerning the latency values obtained with the use of both methods, only concerning amplitude values. both methods were efficient to capture the LLAEP and to control the eye movement artifact. The rejection limit control method produced greater amplitude values.

  14. Vestibular evoked myogenic potential in noise-induced hearing loss

    Directory of Open Access Journals (Sweden)

    Kaushlendra Kumar

    2010-01-01

    Full Text Available Noise affects one′s hearing as well as balance mechanism. The hearing mechanism of the noise-exposed individuals has been extensively studied. However, in view of the poor research focus on the sacculo-collic reflexes, especially in this study area, the present study was undertaken to examine the vestibular evoked myogenic potentials (VEMP in subjects with noise-induced hearing loss (NIHL. A total of 30 subjects (55 ears with NIHL participated in the present study within the age range of 30-40 years. VEMP recordings were done at 99 dBnHL using IHS instrument. The results indicated that as the average pure tone hearing threshold increased, the VEMP latencies were prolonged and peak to peak amplitude was reduced in NIHL subjects. Out of the 55 ears, VEMP was absent in 16 (29.0% ears. The latency was prolonged and the peak to peak amplitude was reduced in 19 (34.6% ears. VEMP results were normal in 20 (36.4% ears. Therefore, VEMP was abnormal or absent in 67% of NIHL subjects in the present study. Hence it can be concluded that the possibility of vestibular dysfunction, specially the saccular pathway, is high in individuals with NIHL. VEMP, a non-invasive and user friendly procedure, can be employed in these individuals to assess sacculo-collic reflex.

  15. Evoked cavernous activity: measuring penile autonomic innervation following pelvic surgery.

    Science.gov (United States)

    Yilmaz, U; Ellis, W; Lange, P; Yang, C

    2006-01-01

    To assess cavernous nerve integrity, we measured evoked cavernous activity (ECA) in 16 men who underwent nerve sparing radical prostatectomy (NS group) and 11 men who underwent non-nerve-sparing surgery (non-NS group). The right median nerve was electrically stimulated and ECA was recorded with two concentric electromyography needles placed into the right and left cavernous bodies. We simultaneously recorded hand and foot sympathetic skin responses (SSRs) as controls. All subjects had recordable SSR, and all subjects following nerve-sparing radical prostatectomy had reproducible ECA. Of the 11 non-NS subjects, eight had no response, indicating interrupted corporal innervation. Three subjects had reproducible ECA, one of whom had a very late latency, suggesting residual innervation was present. The mean latencies of ECA were similar to foot SSR mean latencies (P>0.05), but not to hand SSR latencies. The non-NS group was significantly different from the NS group for the presence of ECA (PECA is a viable method of evaluating the autonomic innervation of the penis.

  16. Early event related fields during visually evoked pain anticipation.

    Science.gov (United States)

    Gopalakrishnan, Raghavan; Burgess, Richard C; Plow, Ela B; Floden, Darlene P; Machado, Andre G

    2016-03-01

    Pain experience is not only a function of somatosensory inputs. Rather, it is strongly influenced by cognitive and affective pathways. Pain anticipatory phenomena, an important limitation to rehabilitative efforts in the chronic state, are processed by associative and limbic networks, along with primary sensory cortices. Characterization of neurophysiological correlates of pain anticipation, particularly during very early stages of neural processing is critical for development of therapeutic interventions. Here, we utilized magnetoencephalography to study early event-related fields (ERFs) in healthy subjects exposed to a 3 s visual countdown task that preceded a painful stimulus, a non-painful stimulus or no stimulus. We found that the first countdown cue, but not the last cue, evoked critical ERFs signaling anticipation, attention and alertness to the noxious stimuli. Further, we found that P2 and N2 components were significantly different in response to first-cues that signaled incoming painful stimuli when compared to non-painful or no stimuli. The findings indicate that early ERFs are relevant neural substrates of pain anticipatory phenomena and could be potentially serve as biomarkers. These measures could assist in the development of neurostimulation approaches aimed at curbing the negative effects of pain anticipation during rehabilitation. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  17. Vestibular evoked myogenic potentials in patients with ankylosing spondylitis.

    Science.gov (United States)

    Özgür, Abdulkadir; Serdaroğlu Beyazal, Münevver; Terzi, Suat; Coşkun, Zerrin Özergin; Dursun, Engin

    2016-10-01

    Ankylosing spondylitis (AS) is a chronic systemic inflammatory disease with unknown etiology. Although sacroiliac joint involvement is the classic sign along with the formed immune mediators, it may result in immune-mediated inner ear disease and may cause damage to the audiovestibular system. Vestibular evoked myogenic potentials (VEMP) is a clinical reflex test used in the diagnosis of vestibular diseases and is performed by recording and evaluating the muscle potentials resulting from the stimulation of the vestibular system with different stimuli. The aim of this study is to evaluate the cervical VEMP test results in AS patients without vestibular symptoms. Thirty-three patients with AS and a control group of 30 healthy volunteers with similar demographic characteristics were evaluated in the study. VEMP wave latency, P13-N23 wave amplitude, and VEMP asymmetry ratio (VAR) values were compared between the groups. The relationship between clinical and laboratory findings of the AS patients and VEMP data were also investigated. Compared with healthy people, this study shows the response rate of patients with ankylosing spondylitis was reduced in the VEMP test, and P13-N23 wave amplitude showed a decrease in AS patients who had VEMP response (p ankylosing spondylitis. The data obtained from this study suggest that AS may lead to decreased sensitivity of the vestibular system.

  18. An evoked potential mapping of transcallosal projections in the cat

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    A. Cukiert

    1989-03-01

    Full Text Available In ten adult cats anesthetized with ketamine hydrochloride the neocortex was exposed and rectangular pulses (1msec, 0.5 Hz and variable intensity were applied to discrete points of one side and transcallosal evoked potentials were recorded from the other. The stimulation and recording positions were determined on a cartesian map of most of the exposable neocortical areas and the potentials were analysed as to their components, voltage and latency. Passive spread and electrotonic potentials and the effects of increasing frequency were also analysed. The results showed large transcallosal potentials in some areas and an increase of potentials in the caudorostral direction, attaining the highest values in anteromedial areas of the suprasylvian gyrus. Confirming anatomical studies, a few silent spots were found in the motor and somesthetic cortex and in restricted posterior regions of the visual cortex, where small or zero voltages occurred. While causing weak contralateral potentials, stimulation of some posterior sites provoked high voltage potentials in anterior regions of the side being stimulated and in the corresponding area of the opposite site. These posterior sites are. poorly interconnected by the corpus callosum. The L-shaped indirect connection described in this work may be involved in some types of epilepsy and may explain the effectiveness of partial callosotomy in their treatment.

  19. Ocular Vestibular Evoked Myogenic Potentials: Where Are We Now?

    Science.gov (United States)

    Dlugaiczyk, Julia

    2017-12-01

    Over the last decade, ocular vestibular evoked myogenic potentials (oVEMPs) have evolved as a new clinical test for dynamic otolith (predominantly utricular) function. The aim of this review is to give an update on the neurophysiological foundations of oVEMPs and their implications for recording and interpreting oVEMP responses in clinical practice. Different lines of anatomical, neurophysiological, and clinical evidence support the notion that oVEMPs measure predominantly contralateral utricular function, while cervical cVEMPs are an indicator of ipsilateral saccular function. Bone-conducted vibration (BCV) in the midline of the forehead at the hairline (Fz) or unilateral air-conducted sound (ACS) are commonly used as stimuli for oVEMPs. It is recommended to apply short stimuli with short rise times for obtaining optimal oVEMP responses. Finally, this review summarizes the clinical application and interpretation of oVEMPs, particularly for vestibular neuritis, Ménière's disease, superior canal dehiscence and "challenging" patients.

  20. Pattern Visual Evoked Potentials Elicited by Organic Electroluminescence Screen

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    Celso Soiti Matsumoto

    2014-01-01

    Full Text Available Purpose. To determine whether organic electroluminescence (OLED screens can be used as visual stimulators to elicit pattern-reversal visual evoked potentials (p-VEPs. Method. Checkerboard patterns were generated on a conventional cathode-ray tube (S710, Compaq Computer Co., USA screen and on an OLED (17 inches, 320 × 230 mm, PVM-1741, Sony, Tokyo, Japan screen. The time course of the luminance changes of each monitor was measured with a photodiode. The p-VEPs elicited by these two screens were recorded from 15 eyes of 9 healthy volunteers (22.0 ± 0.8 years. Results. The OLED screen had a constant time delay from the onset of the trigger signal to the start of the luminescence change. The delay during the reversal phase from black to white for the pattern was 1.0 msec on the cathode-ray tube (CRT screen and 0.5 msec on the OLED screen. No significant differences in the amplitudes of P100 and the implicit times of N75 and P100 were observed in the p-VEPs elicited by the CRT and the OLED screens. Conclusion. The OLED screen can be used as a visual stimulator to elicit p-VEPs; however the time delay and the specific properties in the luminance change must be taken into account.

  1. Development of Brainstem-Evoked Responses in Congenital Auditory Deprivation

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    J. Tillein

    2012-01-01

    Full Text Available To compare the development of the auditory system in hearing and completely acoustically deprived animals, naive congenitally deaf white cats (CDCs and hearing controls (HCs were investigated at different developmental stages from birth till adulthood. The CDCs had no hearing experience before the acute experiment. In both groups of animals, responses to cochlear implant stimulation were acutely assessed. Electrically evoked auditory brainstem responses (E-ABRs were recorded with monopolar stimulation at different current levels. CDCs demonstrated extensive development of E-ABRs, from first signs of responses at postnatal (p.n. day 3 through appearance of all waves of brainstem response at day 8 p.n. to mature responses around day 90 p.n.. Wave I of E-ABRs could not be distinguished from the artifact in majority of CDCs, whereas in HCs, it was clearly separated from the stimulus artifact. Waves II, III, and IV demonstrated higher thresholds in CDCs, whereas this difference was not found for wave V. Amplitudes of wave III were significantly higher in HCs, whereas wave V amplitudes were significantly higher in CDCs. No differences in latencies were observed between the animal groups. These data demonstrate significant postnatal subcortical development in absence of hearing, and also divergent effects of deafness on early waves II–IV and wave V of the E-ABR.

  2. Flash visual evoked potentials in diurnal birds of prey

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    Maurizio Dondi

    2016-07-01

    Full Text Available The objective of this pilot study was to evaluate the feasibility of Flash Visual Evoked Potentials (FVEPs testing in birds of prey in a clinical setting and to describe the protocol and the baseline data for normal vision in this species. FVEP recordings were obtained from 6 normal adult birds of prey: n. 2 Harris’s Hawks (Parabuteo unicinctus, n. 1 Lanner Falcon (Falco biarmicus, n. 2 Gyrfalcons (Falco rusticolus and n. 1 Saker Falcon (Falco cherrug. Before carrying out VEP tests, all animals underwent neurologic and ophthalmic routine examination. Waveforms were analysed to identify reproducible peaks from random variation of baseline. At least three positive and negative peaks were highlighted in all tracks with elevated repeatability. Measurements consisted of the absolute and relative latencies of these peaks (P1, N1, P2, N2, P3, and N3 and their peak-to-peak amplitudes. Both the peak latency and wave morphology achieved from normal animals were similar to those obtained previously in other animal species. This test can be easily and safely performed in a clinical setting in birds of prey and could be useful for an objective assessment of visual function.

  3. Transient and distortion product evoked otoacoustic emissions in premature infants

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    Oliveira, Carlos Augusto Costa Pires de

    2009-09-01

    Full Text Available Introduction: The correlation between the transient (TEOE and distortion product (DPOAE evoked otoacoustic emissions may be useful for the neonatal auditory screening, mainly in premature infants, who have risk indicators for hearing deficiency. There is need for deepening the knowledge regarding this population cochlea features. Objective: To compare the TEOE and DPOAE in premature infants. To analyze the reproducibility in the TEOE, the amplitude and the sign/noise ratio in the TEOE and DPOAE. Method: TEOE and DPOAE were carried out in 50 premature infants. The tests were correlated as for the criterion "pass/failure" and compared according to amplitude and sign/noise ratio parameters. Results: The TEOE were present in 71% of the sample. The frequency of 3kHz presented a better performance in the average reproducibility, amplitude and sign/noise ratio. The DPOAE were present in 97% of the sample. The frequency of 2kHz had a major average amplitude, the values of the sign/noise ratio increased proportionally in the high frequencies. There was a strong correlation between TEOE and DPOAE in the "pass/failure" criterion (p=0.006. Conclusion: The correlation between the TEOE and DPOAE results was significant. But one method compliments the other and both may be used in the TAN.

  4. Humor drawings evoked temporal and spectral EEG processes

    Science.gov (United States)

    Kuo, Hsien-Chu; Chuang, Shang-Wen

    2017-01-01

    Abstract The study aimed to explore the humor processing elicited through the manipulation of artistic drawings. Using the Comprehension–Elaboration Theory of humor as the main research background, the experiment manipulated the head portraits of celebrities based on the independent variables of facial deformation (large/small) and addition of affective features (positive/negative). A 64-channel electroencephalography was recorded in 30 participants while viewing the incongruous drawings of celebrities. The electroencephalography temporal and spectral responses were measured during the three stages of humor which included incongruity detection, incongruity comprehension and elaboration of humor. Analysis of event-related potentials indicated that for humorous vs non-humorous drawings, facial deformation and the addition of affective features significantly affected the degree of humor elicited, specifically: large > small deformation; negative > positive affective features. The N170, N270, N400, N600-800 and N900-1200 components showed significant differences, particularly in the right prefrontal and frontal regions. Analysis of event-related spectral perturbation showed significant differences in the theta band evoked in the anterior cingulate cortex, parietal region and posterior cingulate cortex; and in the alpha and beta bands in the motor areas. These regions are involved in emotional processing, memory retrieval, and laughter and feelings of amusement induced by elaboration of the situation. PMID:28402573

  5. 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.

  6. [Present situation and development of ocular vestibular-evoked myogenic potential].

    Science.gov (United States)

    Hu, Juan; Xu, Min; Zhang, Qing

    2013-04-01

    Myogenic potentials evoked by air conducted sound (ACS), bone conducted vibration (BCV) or galvanic pulses can be recorded with surface electrodes over contracted muscles. These myogenic potentials are of vestibular origin (utricle and saccule) and so these potentials are called vestibular evoked myogenic potentials (VEMPs). Since the vestibular system has projections to many muscle systems, there are many such VEMPs. In this review, we discuss the generated origin, response pathway, waveform characteristics and clinical application of ocular vestibular-evoked myogenic potential (oVEMP).

  7. NLP-12 engages different UNC-13 proteins to potentiate tonic and evoked release.

    Science.gov (United States)

    Hu, Zhitao; Vashlishan-Murray, Amy B; Kaplan, Joshua M

    2015-01-21

    A neuropeptide (NLP-12) and its receptor (CKR-2) potentiate tonic and evoked ACh release at Caenorhabditis elegans neuromuscular junctions. Increased evoked release is mediated by a presynaptic pathway (egl-30 Gαq and egl-8 PLCβ) that produces DAG, and by DAG binding to short and long UNC-13 proteins. Potentiation of tonic ACh release persists in mutants deficient for egl-30 Gαq and egl-8 PLCβ and requires DAG binding to UNC-13L (but not UNC-13S). Thus, NLP-12 adjusts tonic and evoked release by distinct mechanisms. Copyright © 2015 the authors 0270-6474/15/351038-05$15.00/0.

  8. Brainstem auditory evoked responses in an equine patient population: part I--adult horses.

    Science.gov (United States)

    Aleman, M; Holliday, T A; Nieto, J E; Williams, D C

    2014-01-01

    Brainstem auditory evoked response has been an underused diagnostic modality in horses as evidenced by few reports on the subject. To describe BAER findings, common clinical signs, and causes of hearing loss in adult horses. Study group, 76 horses; control group, 8 horses. Retrospective. BAER records from the Clinical Neurophysiology Laboratory were reviewed from the years of 1982 to 2013. Peak latencies, amplitudes, and interpeak intervals were measured when visible. Horses were grouped under disease categories. Descriptive statistics and a posthoc Bonferroni test were performed. Fifty-seven of 76 horses had BAER deficits. There was no breed or sex predisposition, with the exception of American Paint horses diagnosed with congenital sensorineural deafness. Eighty-six percent (n = 49/57) of the horses were younger than 16 years of age. The most common causes of BAER abnormalities were temporohyoid osteoarthropathy (THO, n = 20/20; abnormalities/total), congenital sensorineural deafness in Paint horses (17/17), multifocal brain disease (13/16), and otitis media/interna (4/4). Auditory loss was bilateral and unilateral in 74% (n = 42/57) and 26% (n = 15/57) of the horses, respectively. The most common causes of bilateral auditory loss were sensorineural deafness, THO, and multifocal brain disease whereas THO and otitis were the most common causes of unilateral deficits. Auditory deficits should be investigated in horses with altered behavior, THO, multifocal brain disease, otitis, and in horses with certain coat and eye color patterns. BAER testing is an objective and noninvasive diagnostic modality to assess auditory function in horses. Copyright © 2014 by the American College of Veterinary Internal Medicine.

  9. Serotonergic Hallucinogen-Induced Visual Perceptual Alterations.

    Science.gov (United States)

    Kometer, Michael; Vollenweider, Franz X

    2016-11-30

    Serotonergic hallucinogens, such as lysergic acid diethylamide (LSD), psilocybin, and N,N-dimethyltryptamine (DMT), are famous for their capacity to temporally and profoundly alter an individual's visual experiences. These visual alterations show consistent attributes despite large inter- and intra-individual variances. Many reports document a common perception of colors as more saturated, with increased brightness and contrast in the environment ("Visual Intensifications"). Environmental objects might be altered in size ("Visual illusions") or take on a modified and special meaning for the subject ("Altered self-reference"). Subjects may perceive light flashes or geometrical figures containing recurrent patterns ("Elementary imagery and hallucinations") influenced by auditory stimuli ("Audiovisual synesthesia"), or they may envision images of people, animals, or landscapes ("Complex imagery and hallucinations") without any physical stimuli supporting their percepts. This wide assortment of visual phenomena suggests that one single neuropsychopharmacological mechanism is unlikely to explain such vast phenomenological diversity. Starting with mechanisms that act at the cellular level, the key role of 5-HT2A receptor activation and the subsequent increased cortical excitation will be considered. Next, it will be shown that area specific anatomical and dynamical features link increased excitation to the specific visual contents of hallucinations. The decrease of alpha oscillations by hallucinogens will then be introduced as a systemic mechanism for amplifying internal-driven excitation that overwhelms stimulus-induced excitations. Finally, the hallucinogen-induced parallel decrease of the N170 visual evoked potential and increased medial P1 potential will be discussed as key mechanisms for inducing a dysbalance between global integration and early visual gain that may explain several hallucinogen-induced visual experiences, including visual hallucinations, illusions

  10. Long-term mTOR inhibitors administration evokes altered calcium homeostasis and platelet dysfunction in kidney transplant patients

    OpenAIRE

    López, Esther; Berna-Erro, Alejandro; Bermejo, Nuria; Brull, José María; Martinez, Rocío; Garcia Pino, Guadalupe; Alvarado, Raul; Salido, Ginés María; Rosado, Juan Antonio; Cubero, Juan José; Redondo, Pedro Cosme

    2013-01-01

    The use of the mammal target of rapamycin (mTOR) inhibitors has been consolidated as the therapy of election for preventing graft rejection in kidney transplant patients, despite their immunosuppressive activity is less strong than anti-calcineurin agents like tacrolimus and cyclosporine A. Furthermore, as mTOR is widely expressed, rapamycin (a macrolide antibiotic produced by Streptomyces hygroscopicus) is recommended in patients presenting neoplasia due to its antiproliferative actions. Hen...

  11. Diagnostic accuracy of laser-evoked potentials in diabetic neuropathy.

    Science.gov (United States)

    Di Stefano, Giulia; La Cesa, Silvia; Leone, Caterina; Pepe, Alessia; Galosi, Eleonora; Fiorelli, Marco; Valeriani, Massimiliano; Lacerenza, Marco; Pergolini, Mario; Biasiotta, Antonella; Cruccu, Giorgio; Truini, Andrea

    2017-06-01

    Although the most widely agreed neurophysiological tool for investigating small fiber damage is laser-evoked potential (LEP) recording, no study has documented its diagnostic accuracy. In this clinical, neurophysiological, and skin biopsy study, we collected age-corrected LEP normative ranges, verified the association of LEPs with pinprick sensory disturbances in the typical diabetic mixed fiber polyneuropathy, and assessed the sensitivity and specificity of LEPs in diabetic small fiber neuropathy. From 288 LEP recordings from the face, hand, and foot in 73 healthy subjects, we collected age-corrected normative ranges for LEPs. We then selected 100 patients with mixed-fiber diabetic neuropathy and 25 patients with possible small-fiber diabetic neuropathy. In the 100 patients with mixed fiber neuropathy, we verified how LEP abnormalities were associated with clinically evident pinprick sensory disturbances. In the 25 patients with possible pure small fiber neuropathy, using the skin biopsy for assessing the intraepidermal nerve fiber density as a reference standard, we calculated LEP sensitivity and specificity. In healthy participants, age strongly influenced normative ranges for all LEP variables. By applying age-corrected normative ranges for LEPs, we found that LEPs were strongly associated with pinprick sensory disturbances. In relation to the skin biopsy findings, LEPs yielded 78% sensitivity and 81% specificity in the diagnosis of diabetic small fiber neuropathy. Our study, providing age-corrected normative ranges for the main LEP data and their diagnostic accuracy, helps to make LEPs more reliable as a clinical diagnostic tool, and proposes this technique as a less invasive alternative to skin biopsy for diagnosing diabetic small fiber neuropathy.

  12. EVALUATION OF BRAINSTEM AUDITORY EVOKED POTENTIAL IN MIGRAINE PATIENT

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    Sowmiya R, Vinodha R

    2015-10-01

    Full Text Available Background: Migraine is worldwide common, chronic, Neurovascular disorder, characterized by attacks of severe headache and an Aura involving neurologic symptoms. Its pathogenesis was incompletely understood whether of cortical or brainstem origin. Aim: The present study was undertaken to investigate brainstem auditory functions in Migraine patients. Materials and Methods: The subjects were recruited based on International Headache Society classification for Migraine. Subjects with episodes of headache for at least 2yrs, 2 attacks per month in last quarter year were included in the study. Forty subjects (16 Migraine with Aura & 24 cases – Migraine without aura & forty age / sex matched controls were selected. Brainstem auditory evoked potential was recorded using 4-Channel polygraph (Neuro perfect plus. Electrodes were placed according to 10 – 20 electrode placement system. Auditory stimulus in the form of click sound is delivered through the headphones. Clicks were delivered at a rate of 8-10 /sec. The intensity of the stimulus is set at 30db. About 100 averages were recorded. BAEP waveforms – Wave I, III & V latencies and the interpeak latencies were measured. The results were analysed statistically using student‘t’ test. Results: BAEP recording shows significant prolongation in latencies of Wave I, III & V and the Interpeak latency (IPL I-III, III-V & I-V in Migraine with aura. In Migraine without aura, there was significant prolongation of Wave I, III & V and III-V & I-VIPL (P<0.05. Conclusion: Prolongation suggests that there is involvement of brainstem structures in Migraine, thus BAEP can be used as an effective tool in evaluation of Migraine.

  13. Brainstem auditory-evoked potential in Boxer dogs

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    Mariana Isa Poci Palumbo

    2014-10-01

    Full Text Available Brainstem auditory-evoked potential (BAEP has been widely used for different purposes in veterinary practice and is commonly used to identify inherited deafness and presbycusis. In this study, 43 Boxer dogs were evaluated using the BAEP. Deafness was diagnosed in 3 dogs (2 bilateral and 1 unilateral allowing the remaining 40 Boxers to be included for normative data analysis including an evaluation on the influence of age on the BAEP. The animals were divided into 2 groups of 20 Boxers each based on age. The mean age was 4.54 years (range, 1-8 in group I, and 9.83 years (range, 8.5-12 in group II. The mean latency for I, III, and V waves were 1.14 (±0.07, 2.64 (±0.11, and 3.48 (±0.10 ms in group I, and 1.20 (±0.12, 2.73 (±0.15, and 3.58 (±0.22 ms in group II, respectively. The mean inter-peak latencies for the I-III, III-V and I-V intervals were 1.50 (±0.15, 0.84 (±0.15, and 2.34 (±0.11 ms in group I, and 1.53 (±0.16, 0.85 (±0.15, and 2.38 (±0.19 ms in group II, respectively. Latencies of waves I and III were significant different between group I and II. For the I-III, III-V and I-V intervals, no significant differences were observed between the 2 groups. As far as we know, this is the first normative study of BAEP obtained from Boxer dogs.

  14. Visual Evoked Potential to Assess Retinopathy in Gestational Diabetes Mellitus.

    Science.gov (United States)

    Hari Kumar, K V S; Ahmad, F M H; Sood, Sandeep; Mansingh, Sudhir

    2016-04-01

    We evaluated for early retinopathy using the visual evoked potential (VEP) in patients with gestational diabetes mellitus (GDM) and type 2 diabetes mellitus during pregnancy. All patients with GDM and type 2 diabetes seen between June and October of 2014 were included in this cross-sectional, observational study. Patients with secondary diabetes, ocular or major illness were excluded from the study. VEP was recorded in both eyes to derive prominent positive peak latency (P100), amplitude and initial negative deflection (N75) latency. The data were compared with 10 gestational age-matched controls with normal glucose tolerance. Appropriate statistical methods were used for comparison among the 3 groups. The study participants (40 with GDM, 10 with type 2 diabetes, 10 with normal glucose tolerance) had a median (25th to 75th interquartile range) age of 26 (24.3, 30) years, a gestational age of 24.5 (21, 27) weeks and weights of 66.8 (63.4, 71.5) kg. The P100 latencies were comparable among the 3 groups (p=0.0577). However, patients with any diabetes (GDM and type 2 diabetes) had prolonged P100 latencies (p=0.0139) and low P100 amplitudes (p=0.0391) in comparison to controls. P100 latency showed a direct correlation with hyperglycemia (p=0.0118). Our data showed that VEP abnormalities are detectable even in the short-term hyperglycemia of GDM and type 2 diabetes. Copyright © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

  15. Morphological changes associated with the genesis and development of an excitatory glutemergic synapse: An integrated framework model

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    Venkateswaran Nagarajan

    2014-04-01

    Full Text Available The genesis of an excitatory synapse has its inception when a dendritic filopodium makes a tactile contact with a presynaptic specialisation (bouton. The subsequent maturation of the synapse takes place via a series of interrelated biochemical and biophysical signalling pathways which controls the actin polymerisation in the presynaptic and the postsynaptic sites. Although individual models of many of these signalling transductions have been proposed, a holistic model integrating the various signalling pathways to the morphological plasticity associated with the genesis and development of synapses has not. In this poster an attempt has been made towards establishing a framework for an integrated model such as the one aforementioned, encompassing several signalling pathways which control the morphology and the efficacy of the synapse. Predominant pathways include those triggered by NMDA and AMPA receptors, Trkb-BDNF, Integrin and Epherin. Also, steps towards a model that elucidates the change in shape of the synapse carried out by zonal actin polymerisation (ZAP governed by the "wastage" of neurotransmitters during exo cum endocytosis processes and the assimilation of the postsynaptic density (PSD and cell adhesion molecules with emphasis on Neurexin-Neuriligin, have been explored. The cannabinoid receptors in the PAZ have extracellular lipophilic domains. Endocannabinoid receptors are triggered by the retrograde signalling cues which negatively affect the cAMP dependent mechanisms. Apart from this, autoreceptors also pilot a feedback mechanism via secondary messengers with Ca 2+ ion concentration and neurotransmitter concentration in the synaptic cleft as its stakeholders. Feedback signals of autoreceptors which functions in accordance to “Lock and Key Mechanism” plays a vital role in fine-tuning the plasticity of the synapse and in controlling the presynaptic release probability by invoking PKA dependent pathways. In a future continuation

  16. Posterior Orbitofrontal and Anterior Cingulate Pathways to the Amygdala Target Inhibitory and Excitatory Systems with Opposite Functions.

    Science.gov (United States)

    Zikopoulos, Basilis; Höistad, Malin; John, Yohan; Barbas, Helen

    2017-05-17

    The bidirectional dialogue of the primate posterior orbitofrontal cortex (pOFC) with the amygdala is essential in cognitive-emotional functions. The pOFC also sends a uniquely one-way excitatory pathway to the amygdalar inhibitory intercalated masses (IM), which inhibit the medial part of the central amygdalar nucleus (CeM). Inhibition of IM has the opposite effect, allowing amygdalar activation of autonomic structures and emotional arousal. Using multiple labeling approaches to identify pathways and their postsynaptic sites in the amygdala in rhesus monkeys, we found that the anterior cingulate cortex innervated mostly the basolateral and CeM amygdalar nuclei, poised to activate CeM for autonomic arousal. By contrast, a pathway from pOFC to IM exceeded all other pathways to the amygdala by density and size and proportion of large and efficient terminals. Moreover, whereas pOFC terminals in IM innervated each of the three distinct classes of inhibitory neurons, most targeted neurons expressing dopamine- and cAMP-regulated phosphoprotein (DARPP-32+), known to be modulated by dopamine. The predominant pOFC innervation of DARPP-32+ neurons suggests activation of IM and inhibition of CeM, resulting in modulated autonomic function. By contrast, inhibition of DARPP-32 neurons in IM by high dopamine levels disinhibits CeM and triggers autonomic arousal. The findings provide a mechanism to help explain how a strong pOFC pathway, which is poised to moderate activity of CeM, through IM, can be undermined by the high level of dopamine during stress, resulting in collapse of potent inhibitory mechanisms in the amygdala and heightened autonomic drive, as seen in chronic anxiety disorders. SIGNIFICANCE STATEMENT The dialogue between prefrontal cortex and amygdala allows thoughts and emotions to influence actions. The posterior orbitofrontal cortex sends a powerful pathway that targets a special class of amygdalar intercalated mass (IM) inhibitory neurons, whose wiring may help

  17. 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

  18. Prestimulus amplitudes modulate P1 latencies and evoked traveling alpha waves

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    Nicole Alexandra Himmelstoss

    2015-05-01

    Full Text Available Traveling waves have been well documented in the ongoing, and more recently also in the evoked EEG. In the present study we investigate what kind of physiological process might be responsible for inducing an evoked traveling wave. We used a semantic judgment task which already proved useful to study evoked traveling alpha waves that coincide with the appearance of the P1 component. We found that the P1 latency of the leading electrode is significantly correlated with prestimulus amplitude size and that this event is associated with a transient change in alpha frequency. We assume that cortical background excitability, as reflected by an increase in prestimulus amplitude, is responsible for the observed change in alpha frequency and the initiation of an evoked traveling trajectory.

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

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    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.

  20. Assessment evaluation of transient evoked otoacoustic emission by contralateral suppression in tinnitus patient with normal hearing

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    Helnaz Mokrian

    2014-01-01

    Conclusion: The suppression of the transient evoked otoacoustic emission by contralateral white noise did not reach statistically significant levels in tinnitus patients while the amplitude in control group reduced significantly.

  1. Dynamic Lateralization of Pupil Dilation Evoked by Locus Coeruleus Activation Results from Sympathetic, Not Parasympathetic, Contributions

    Directory of Open Access Journals (Sweden)

    Yang Liu

    2017-09-01

    Full Text Available Pupil size is collectively controlled by the sympathetic dilator and parasympathetic sphincter muscles. Locus coeruleus (LC activation has been shown to evoke pupil dilation, but how the sympathetic and parasympathetic pathways contribute to this dilation remains unknown. We examined pupil dilation elicited by LC activation in lightly anesthetized rats. Unilateral LC activation evoked bilateral but lateralized pupil dilation; i.e., the ipsilateral dilation was significantly larger than the contralateral dilation. Surgically blocking the ipsilateral, but not contralateral, sympathetic pathway significantly reduced lateralization, suggesting that lateralization is mainly due to sympathetic contribution. Moreover, we found that sympathetic, but not parasympathetic, contribution is correlated with LC activation frequency. Together, our results unveil the frequency-dependent contributions of the sympathetic and parasympathetic pathways to LC activation-evoked pupil dilation and suggest that lateralization in task-evoked pupil dilations may be used as a biomarker for autonomic tone.

  2. Clinical Evaluation of the Vestibular Nerve Using Vestibular Evoked Myogenic Potentials.

    Science.gov (United States)

    Bogle, Jamie M

    2018-01-01

    Vestibular evoked myogenic potentials are currently the most clinically accessible method to evaluate the otolith reflex pathways. These responses provide unique information regarding the status of the utriculo-ocular and sacculo-collic reflex pathways, information that has previously been unavailable. Vestibular evoked myogenic potentials are recorded from tonically contracted target muscles known to be innervated by these respective otolith organs. Diagnosticians can use vestibular evoked myogenic potentials to better evaluate the overall integrity of the inner ear and neural pathways; however, there are specific considerations for each otolith reflex protocol. In addition, specific patient populations may require protocol variations to better evaluate atypical function of the inner ear organs, vestibular nerve transmission, or subsequent reflex pathways. This is a review of the clinical application and interpretation of cervical and ocular vestibular evoked myogenic potentials.

  3. Music‐evoked emotions: principles, brain correlates, and implications for therapy

    National Research Council Canada - National Science Library

    Koelsch, Stefan

    2015-01-01

    ... 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...

  4. 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

  5. Auditory evoked responses in musicians during passive vowel listening are modulated by functional connectivity between bilateral auditory-related brain regions.

    Science.gov (United States)

    Kühnis, Jürg; Elmer, Stefan; Jäncke, Lutz

    2014-12-01

    Currently, there is striking evidence showing that professional musical training can substantially alter the response properties of auditory-related cortical fields. Such plastic changes have previously been shown not only to abet the processing of musical sounds, but likewise spectral and temporal aspects of speech. Therefore, here we used the EEG technique and measured a sample of musicians and nonmusicians while the participants were passively exposed to artificial vowels in the context of an oddball paradigm. Thereby, we evaluated whether increased intracerebral functional connectivity between bilateral auditory-related brain regions may promote sensory specialization in musicians, as reflected by altered cortical N1 and P2 responses. This assumption builds on the reasoning that sensory specialization is dependent, at least in part, on the amount of synchronization between the two auditory-related cortices. Results clearly revealed that auditory-evoked N1 responses were shaped by musical expertise. In addition, in line with our reasoning musicians showed an overall increased intracerebral functional connectivity (as indexed by lagged phase synchronization) in theta, alpha, and beta bands. Finally, within-group correlative analyses indicated a relationship between intracerebral beta band connectivity and cortical N1 responses, however only within the musicians' group. Taken together, we provide first electrophysiological evidence for a relationship between musical expertise, auditory-evoked brain responses, and intracerebral functional connectivity among auditory-related brain regions.

  6. Cervical intraspinal microstimulation evokes robust forelimb movements before and after injury

    Science.gov (United States)

    Sunshine, Michael D.; Cho, Frances S.; Lockwood, Danielle R.; Fechko, Amber S.; Kasten, Michael R.; Moritz, Chet T.

    2013-06-01

    Objective. Intraspinal microstimulation (ISMS) is a promising method for reanimating paralyzed limbs following neurological injury. ISMS within the cervical and lumbar spinal cord is capable of evoking a variety of highly-functional movements prior to injury, but the ability of ISMS to evoke forelimb movements after cervical spinal cord injury is unknown. Here we examine the forelimb movements and muscles activated by cervical ISMS both before and after contusion injury. Approach. We documented the forelimb muscles activated and movements evoked via systematic stimulation of the rodent cervical spinal cord both before injury and three, six and nine weeks following a moderate C4/C5 lateralized contusion injury. Animals were anesthetized with isoflurane to permit construction of somatotopic maps of evoked movements and quantify evoked muscle synergies between cervical segments C3 and T1. Main results. When ISMS was delivered to the cervical spinal cord, a variety of responses were observed at 68% of locations tested, with a spatial distribution that generally corresponded to the location of motor neuron pools. Stimulus currents required to achieve movement and the number of sites where movements could be evoked were unchanged by spinal cord injury. A transient shift toward extension-dominated movements and restricted muscle synergies were observed at three and six weeks following injury, respectively. By nine weeks after injury, however, ISMS-evoked patterns were similar to spinally-intact animals. Significance. The results demonstrate the potential for cervical ISMS to reanimate hand and arm function following spinal cord injury. Robust forelimb movements can be evoked both before and during the chronic stages of recovery from a clinically relevant and sustained cervical contusion injury.

  7. Visual evoked potentials in Negro carriers of the gene for tyrosinase positive oculocutaneous albinism.

    Science.gov (United States)

    Castle, D; Kromberg, J; Kowalsky, R; Moosa, R; Gillman, N; Zwane, E; Fritz, V

    1988-01-01

    Visual evoked potential testing was performed on 15 Negro carriers of the gene for tyrosinase positive oculocutaneous albinism in order to detect whether they have the same visual pathway decussation anomalies as do homozygotes. No subject showed 01-02 asymmetry on monocular testing, indicating that decussation follows the normal pattern. It is concluded that visual evoked potential testing is probably not useful in the detection of Negroes heterozygous for the gene for tyrosinase positive oculocutaneous albinism. PMID:3148727

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

    OpenAIRE

    Liila Taruffi; Stefan Koelsch

    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 factor...

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

    Directory of Open Access Journals (Sweden)

    Flávia V. A. Medeiros

    2015-12-01

    Full Text Available BACKGROUND: 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. OBJECTIVE: To investigate the effects of skinfold thickness (SFT on maximal NMES current intensity, NMES-evoked torque, and NMES-induced discomfort. METHOD: 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. RESULTS: 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. CONCLUSION: 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.

  10. Transient evoked otoacoustic emissions testing for screening of sensorineural deafness in puppies

    OpenAIRE

    McBrearty, A; Penderis, J

    2011-01-01

    Background: Transient evoked otoacoustic emissions (TEOAE) are widely used for human neonatal deafness screening, but have not been reported for clinical use in dogs. \\ud \\ud Hypothesis/Objectives: To investigate the feasibility of TEOAE testing in conscious puppies and the ability of TEOAE testing to correctly identify deaf and hearing ears, as defined by brainstem auditory evoked response (BAER). \\ud \\ud Animals: Forty puppies from 10 litters. \\ud \\ud Methods: Prospective study on puppies p...

  11. Effect of eye lateralization on contralateral suppression of transient evoked otoacoustic emissions

    OpenAIRE

    SOI, D.; Brambilla, D; COMIOTTO, E.; DI Berardino, F; Filipponi, E.; Socci, M; SPREAFICO, E.; Forti, S.; CESARANI, A.

    2012-01-01

    SUMMARY Several studies have previously demonstrated that postural changes modify evoked otoacoustic emission. In order to evaluate a possible interaction between eye muscles and ciliated cells in the inner ear, we studied the effects of eye lateralization on the contralateral suppression of transient evoked otoacoustic emissions (TEOAEs). Thirty-eight normal hearing subjects with TEOAEs were recruited. Their TEAOEs at threshold level were recorded with contralateral suppression (white noise)...

  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. The Loudness Dependence of Auditory Evoked Potentials (LDAEP) in individuals at risk for developing bipolar disorders and schizophrenia.

    Science.gov (United States)

    Hagenmuller, Florence; Heekeren, Karsten; Meier, Magali; Theodoridou, Anastasia; Walitza, Susanne; Haker, Helene; Rössler, Wulf; Kawohl, Wolfram

    2016-02-01

    The Loudness Dependence of Auditory Evoked Potentials (LDAEP) is considered as an indicator of central serotonergic activity. Alteration of serotonergic neurotransmission was reported in bipolar disorders and schizophrenia. In line with previous reports on clinically manifest disorders, we expected a weaker LDAEP in subjects at risk for bipolar disorders and schizophrenia compared to healthy controls. We analyzed LDAEP of individuals at risk for developing bipolar disorders (n=27), with high-risk status (n=74) and ultra-high-risk status for schizophrenia (n=86) and healthy controls (n=47). The LDAEP did not differ between subjects at risk for schizophrenia or bipolar disorders and controls. Among subjects without medication (n=122), the at-risk-bipolar group showed a trend towards a weaker LDAEP than both the high-risk and the ultra-high-risk groups for schizophrenia. The LDAEP did not appear as a vulnerability marker for schizophrenia or bipolar disorders. This suggests that an altered LDAEP may not be measurable until the onset of clinically manifest disorder. However, the hypothesis that pathogenic mechanisms leading to bipolar disorders may differ from those leading to schizophrenia is supported. This is the first study investigating LDAEP in a population at risk for bipolar disorders. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  14. Bypass or not? Adjustment of surgical strategies according to motor evoked potential changes in large middle cerebral artery aneurysm surgery.

    Science.gov (United States)

    Chen, Liang; Lang, Liqin; Zhou, Liangfu; Song, Donglei; Mao, Ying

    2012-02-01

    To report the use of neuroelectrophysiologic monitoring to alter the course in aneurysm surgery to minimize postoperative infarction and bypass-related adverse events. Two patients with large middle cerebral artery (MCA) aneurysms were admitted to the authors' hospital. Direct clipping seemed to be difficult, and postoperative paralysis was not rare in the authors' experience owing to prolonged temporal occlusion of the parent artery. Balloon test occlusion (BTO) was positive in one patient, who developed paralysis and aphasia 3 minutes after balloon occlusion of the feeding M1 artery. A bypass procedure seemed to be inevitable in both patients. Motor evoked potentials (MEPs) and sensory evoked potentials (SEPs) were used for monitoring during the operation. For the patient with a positive BTO result, MEP waves did not change until 17 minutes after temporary clip placement. The aneurysm was clipped, and the occlusion time was 24 minutes. MEP waves recovered quickly after reperfusion. In the other patient, there were early changes in MEP waves after temporary clipping. After bypass construction from the temporal artery to the inferior M2 trunk, the time window of safe occlusion was prolonged to 7-8 minutes. Both the aneurysm and the bypassed branch were obliterated, and the clip reconstruction was done to preserve the flow from M1 to the superior M2 trunk. Permanent postoperative disability did not occur in either patient. Intraoperative physiologic monitoring is a complementary method to preoperative BTO to evaluate the window of safe occlusion with high reliability. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Chronic Compression of the Dorsal Root Ganglion Enhances Mechanically Evoked Pain Behavior and the Activity of Cutaneous Nociceptors in Mice.

    Directory of Open Access Journals (Sweden)

    Tao Wang

    Full Text Available Radicular pain in humans is usually caused by intraforaminal stenosis and other diseases affecting the spinal nerve, root, or dorsal root ganglion (DRG. Previous studies discovered that a chronic compression of the DRG (CCD induced mechanical allodynia in rats and mice, with enhanced excitability of DRG neurons. We investigated whether CCD altered the pain-like behavior and also the responses of cutaneous nociceptors with unmyelinated axons (C-fibers to a normally aversive punctate mechanical stimulus delivered to the hairy skin of the hind limb of the mouse. The incidence of a foot shaking evoked by indentation of the dorsum of foot with an aversive von Frey filament (tip diameter 200 μm, bending force 20 mN was significantly higher in the foot ipsilateral to the CCD surgery as compared to the contralateral side on post-operative days 2 to 8. Mechanically-evoked action potentials were electrophysiologically recorded from the L3 DRG, in vivo, from cell bodies visually identified as expressing a transgenically labeled fluorescent marker (neurons expressing either the receptor MrgprA3 or MrgprD. After CCD, 26.7% of MrgprA3+ and 32.1% MrgprD+ neurons exhibited spontaneous activity (SA, while none of the unoperated control neurons had SA. MrgprA3+ and MrgprD+ neurons in the compressed DRG exhibited, in comparison with neurons from unoperated control mice, an increased response to the punctate mechanical stimuli for each force applied (6, 20, 40, and 80 mN. We conclude that CCD produced both a behavioral hyperalgesia and an enhanced response of cutaneous C-nociceptors to aversive punctate mechanical stimuli.

  16. Early and late activity in somatosensory cortex reflects changes in bodily self-consciousness: an evoked potential study.

    Science.gov (United States)

    Aspell, J E; Palluel, E; Blanke, O

    2012-08-02

    How can we investigate the brain mechanisms underlying self-consciousness? Recent behavioural studies on multisensory bodily perception have shown that multisensory conflicts can alter bodily self-consciousness such as in the "full body illusion" (FBI) in which changes in self-identification with a virtual body and tactile perception are induced. Here we investigated whether experimental changes in self-identification during the FBI are accompanied by activity changes in somatosensory cortex by recording somatosensory-evoked potentials (SEPs). To modulate self-identification, participants were filmed by a video camera from behind while their backs were stroked, either synchronously (illusion condition) or asynchronously (control condition) with respect to the stroking seen on their virtual body. Tibial nerve SEPs were recorded during the FBI and analysed using evoked potential (EP) mapping. Tactile mislocalisation was measured using the crossmodal congruency task. SEP mapping revealed five sequential periods of brain activation during the FBI, of which two differed between the illusion condition and the control condition. Activation at 30-50 ms (corresponding to the P40 component) in primary somatosensory cortex was stronger in the illusion condition. A later activation at ∼110-200 ms, likely originating in higher-tier somatosensory regions in parietal cortex, was stronger and lasted longer in the control condition. These data show that changes in bodily self-consciousness modulate activity in primary and higher-tier somatosensory cortex at two distinct processing steps. We argue that early modulations of primary somatosensory cortex may be a consequence of (1) multisensory integration of synchronous vs. asynchronous visuo-tactile stimuli and/or (2) differences in spatial attention (to near or far space) between the conditions. The later activation in higher-tier parietal cortex (and potentially other regions in temporo-parietal and frontal cortex) likely

  17. 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

  18. Neuromodulation of evoked muscle potentials induced by epidural spinal-cord stimulation in paralyzed individuals.

    Science.gov (United States)

    Sayenko, Dimitry G; Angeli, Claudia; Harkema, Susan J; Edgerton, V Reggie; Gerasimenko, Yury P

    2014-03-01

    Epidural stimulation (ES) of the lumbosacral spinal cord has been used to facilitate standing and voluntary movement after clinically motor-complete spinal-cord injury. It seems of importance to examine how the epidurally evoked potentials are modulated in the spinal circuitry and projected to various motor pools. We hypothesized that chronically implanted electrode arrays over the lumbosacral spinal cord can be used to assess functionally spinal circuitry linked to specific motor pools. The purpose of this study was to investigate the functional and topographic organization of compound evoked potentials induced by the stimulation. Three individuals with complete motor paralysis of the lower limbs participated in the study. The evoked potentials to epidural spinal stimulation were investigated after surgery in a supine position and in one participant, during both supine and standing, with body weight load of 60%. The stimulation was delivered with intensity from 0.5 to 10 V at a frequency of 2 Hz. Recruitment curves of evoked potentials in knee and ankle muscles were collected at three localized and two wide-field stimulation configurations. Epidural electrical stimulation of rostral and caudal areas of lumbar spinal cord resulted in a selective topographical recruitment of proximal and distal leg muscles, as revealed by both magnitude and thresholds of the evoked potentials. ES activated both afferent and efferent pathways. The components of neural pathways that can mediate motor-evoked potentials were highly dependent on the stimulation parameters and sensory conditions, suggesting a weight-bearing-induced reorganization of the spinal circuitries.

  19. Characterization of Motor and Somatosensory Evoked Potentials in the Yucatan Micropig Using Transcranial and Epidural Stimulation.

    Science.gov (United States)

    Benavides, Francisco D; Santamaria, Andrea J; Bodoukhin, Nikita; Guada, Luis G; Solano, Juan P; Guest, James D

    2017-09-15

    Yucatan micropigs have brain and spinal cord dimensions similar to humans and are useful for certain spinal cord injury (SCI) translational studies. Micropigs are readily trained in behavioral tasks, allowing consistent testing of locomotor loss and recovery. However, there has been little description of their motor and sensory pathway neurophysiology. We established methods to assess motor and sensory cortical evoked potentials in the anesthetized, uninjured state. We also evaluated epidurally evoked motor and sensory stimuli from the T6 and T9 levels, spanning the intended contusion injury epicenter. Response detection frequency, mean latency and amplitude values, and variability of evoked potentials were determined. Somatosensory evoked potentials were reliable and best detected during stimulation of peripheral nerve and epidural stimulation by referencing the lateral cortex to midline Fz. The most reliable hindlimb motor evoked potential (MEP) occurred in tibialis anterior. We found MEPs in forelimb muscles in response to thoracic epidural stimulation likely generated from propriospinal pathways. Cranially stimulated MEPs were easier to evoke in the upper limbs than in the hindlimbs. Autopsy studies revealed substantial variations in cortical morphology between animals. This electrophysiological study establishes that neurophysiological measures can be reliably obtained in micropigs in a time frame compatible with other experimental procedures, such as SCI and transplantation. It underscores the need to better understand the motor control pathways, including the corticospinal tract, to determine which therapeutics are suitable for testing in the pig model.

  20. Spiking and Excitatory/Inhibitory Input Dynamics of Barrel Cells in Response to Whisker Deflections of Varying Velocity and Angular Direction.

    Science.gov (United States)

    Patel, Mainak

    2018-01-15

    The spiking of barrel regular-spiking (RS) cells is tuned for both whisker deflection direction and velocity. Velocity tuning arises due to thalamocortical (TC) synchrony (but not spike quantity) varying with deflection velocity, coupled with feedforward inhibition, while direction selectivity is not fully understood, though may be due partly to direction tuning of TC spiking. Data show that as deflection direction deviates from the preferred direction of an RS cell, excitatory input to the RS cell diminishes minimally, but temporally shifts to coincide with the time-lagged inhibitory input. This work constructs a realistic large-scale model of a barrel; model RS cells exhibit velocity and direction selectivity due to TC input dynamics, with the experimentally observed sharpening of direction tuning with decreasing velocity. The model puts forth the novel proposal that RS→RS synapses can naturally and simply account for the unexplained direction dependence of RS cell inputs - as deflection direction deviates from the preferred direction of an RS cell, and TC input declines, RS→RS synaptic transmission buffers the decline in total excitatory input and causes a shift in timing of the excitatory input peak from the peak in TC input to the delayed peak in RS input. The model also provides several experimentally testable predictions on the velocity dependence of RS cell inputs. This model is the first, to my knowledge, to study the interaction of direction and velocity and propose physiological mechanisms for the stimulus dependence in the timing and amplitude of RS cell inputs. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. Identification of a New Class of Selective Excitatory Amino Acid Transporter Subtype 1 (EAAT1) Inhibitors Followed by a Structure-Activity-Relationship Study

    DEFF Research Database (Denmark)

    Hansen, Stinne Wessel; Erichsen, Mette Norman; Fu, Bingru

    2016-01-01

    Screening of a small compound library at the three excitatory amino acid transporter subtypes 1–3 (EAAT1–3) resulted in the identification of compound (Z)-4-chloro-3-(5-((3-(2-ethoxy-2-oxoethyl)-2,4-dioxothiazolidin-5-ylidene)methyl)furan-2-yl)benzoic acid (1a) that exhibited a distinct preference...... available pharmacological tools in the EAAT field but also substantiates the notion that EAAT ligands not derived from α-amino acids hold considerable potential in terms of subtype-selective modulation of the transporters....

  2. 4,4-Dimethyl- and diastereomeric 4-hydroxy-4-methyl-(2S)-glutamate analogues display distinct pharmacological profiles at ionotropic glutamate receptors and excitatory amino acid transporters

    DEFF Research Database (Denmark)

    Bunch, Lennart; Pickering, Darryl S; Gefflaut, Thierry

    2009-01-01

    this approach has provided important insight into the structure-activity relationships (SAR) for ionotropic and metabotropic glutamate receptors (iGluRs and mGluRs), as well as the excitatory amino acid transporters (EAATs). In this work, three 4,4-disubstituted Glu analogues 1-3, which are hybrid structures......Subtype-selective ligands are of great interest to the scientific community, as they provide a tool for investigating the function of one receptor or transporter subtype when functioning in its native environment. Several 4-substituted (S)-glutamate (Glu) analogues were synthesized, and altogether...

  3. mGluR5 in cortical excitatory neurons exerts both cell autonomous and nonautonomous influences on cortical somatosensory circuit formation

    OpenAIRE

    Ballester-Rosado, Carlos J.; Albright, Michael J.; Wu, Chia-Shan; Liao, Chun-Chieh; Zhu, Jie; Xu, Jian; Lee, Li-Jen; Lu, Hui-Chen

    2010-01-01

    Glutamatergic neurotransmission plays important roles in sensory map formation. The absence of the group I metabotropic glutamate receptor 5 (mGluR5) leads to abnormal sensory map formation throughout the mouse somatosensory pathway. To examine the role of cortical mGluR5 expression on barrel map formation, we generated cortex-specific mGluR5 KO mice. Eliminating mGluR5 function solely in cortical excitatory neurons, not only affects the whisker-related organization of cortical neurons (barre...

  4. [Auditory evoked potential and personality traits in chronic primary insomniacs].

    Science.gov (United States)

    Shen, Jian; Shui, Ren-de; Feng, Lei; Liu, Yu-Hong; He, Wei; Huang, Jing-Yi; Wang, Wei

    2009-05-01

    To investigate the personality traits and intensity dependence of auditory evoked potentials (A