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Sample records for thalamic neurons relationship

  1. Intrinsic properties and neuropharmacology of midline paraventricular thalamic nucleus neurons.

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    Miloslav eKolaj

    2014-04-01

    Full Text Available Neurons in the midline and intralaminar thalamic nuclei are components of an interconnected brainstem, limbic and prefrontal cortex neural network that is engaged during arousal, vigilance, motivated and addictive behaviors, and stress. To better understand the cellular mechanisms underlying these functions, here we review some of the recently characterized electrophysiological and neuropharmacological properties of neurons in the paraventricular thalamic nucleus (PVT, derived from whole cell patch clamp recordings in acute rat brain slice preparations. PVT neurons display firing patterns and ionic conductances (IT and IH that exhibit significant diurnal change. Their resting membrane potential is maintained by various ionic conductances that include inward rectifier (Kir, hyperpolarization-activated nonselective cation (HCN and TWIK-related acid sensitive (TASK K+ channels. Firing patterns are regulated by high voltage-activated (HVA and low voltage-activated (LVA Ca2+ conductances. Moreover, transient receptor potential (TRP-like nonselective cation channels together with Ca2+- and Na+-activated K+ conductances (KCa; KNa contribute to unique slow afterhyperpolarizing potentials (sAHPs that are generally not detectable in lateral thalamic or reticular thalamic nucleus neurons. We also report on receptor-mediated actions of GABA, glutamate, monoamines and several neuropeptides: arginine vasopressin, gastrin-releasing peptide, thyrotropin releasing hormone and the orexins (hypocretins. This review represents an initial survey of intrinsic and transmitter-sensitive ionic conductances that are deemed to be unique to this population of midline thalamic neurons, information that is fundamental to an appreciation of the role these thalamic neurons may play in normal central nervous system (CNS physiology and in CNS disorders that involve the dorsomedial thalamus.

  2. Differential Responses of Thalamic Reticular Neurons to Nociception in Freely Behaving Mice

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    Huh, Yeowool; Cho, Jeiwon

    2016-01-01

    Pain serves an important protective role. However, it can also have debilitating adverse effects if dysfunctional, such as in pathological pain conditions. As part of the thalamocortical circuit, the thalamic reticular nucleus (TRN) has been implicated to have important roles in controlling nociceptive signal transmission. However studies on how TRN neurons, especially how TRN neuronal subtypes categorized by temporal bursting firing patterns—typical bursting, atypical bursting and non-bursting TRN neurons—contribute to nociceptive signal modulation is not known. To reveal the relationship between TRN neuronal subtypes and modulation of nociception, we simultaneously recorded behavioral responses and TRN neuronal activity to formalin induced nociception in freely moving mice. We found that typical bursting TRN neurons had the most robust response to nociception; changes in tonic firing rate of typical TRN neurons exactly matched changes in behavioral nociceptive responses, and burst firing rate of these neurons increased significantly when behavioral nociceptive responses were reduced. This implies that typical TRN neurons could critically modulate ascending nociceptive signals. The role of other TRN neuronal subtypes was less clear; atypical bursting TRN neurons decreased tonic firing rate after the second peak of behavioral nociception and the firing rate of non-bursting TRN neurons mostly remained at baseline level. Overall, our results suggest that different TRN neuronal subtypes contribute differentially to processing formalin induced sustained nociception in freely moving mice. PMID:27917114

  3. Changes in Activity of the Same Thalamic Neurons to Repeated Nociception in Behaving Mice.

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    Huh, Yeowool; Cho, Jeiwon

    2015-01-01

    The sensory thalamus has been reported to play a key role in central pain sensory modulation and processing, but its response to repeated nociception at thalamic level is not well known. Current study investigated thalamic response to repeated nociception by recording and comparing the activity of the same thalamic neuron during the 1st and 2nd formalin injection induced nociception, with a week interval between injections, in awake and behaving mice. Behaviorally, the 2nd injection induced greater nociceptive responses than the 1st. Thalamic activity mirrored these behavioral changes with greater firing rate during the 2nd injection. Analysis of tonic and burst firing, characteristic firing pattern of thalamic neurons, revealed that tonic firing activity was potentiated while burst firing activity was not significantly changed by the 2nd injection relative to the 1st. Likewise, burst firing property changes, which has been consistently associated with different phases of nociception, were not induced by the 2nd injection. Overall, data suggest that repeated nociception potentiated responsiveness of thalamic neurons and confirmed that tonic firing transmits nociceptive signals.

  4. Stereological analysis of the mediodorsal thalamic nucleus in schizophrenia: volume, neuron number, and cell types

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    Dorph-Petersen, Karl-Anton; Pierri, Joseph N; Sun, Zhuoxin

    2004-01-01

    The mediodorsal thalamic nucleus (MD) is the principal relay nucleus for the prefrontal cortex, a brain region thought to be dysfunctional in schizophrenia. Several, but not all, postmortem studies of the MD in schizophrenia have reported decreased volume and total neuronal number. However......, it is not clear whether the findings are specific for schizophrenia nor is it known which subtypes of thalamic neurons are affected. We studied the left MD in 11 subjects with schizophrenia, 9 control subjects, and 12 subjects with mood disorders. Based on morphological criteria, we divided the neurons into two...... subclasses, presumably corresponding to projection neurons and local circuit neurons. We estimated MD volume and the neuron number of each subclass using methods based on modern unbiased stereological principles. We also estimated the somal volumes of each subclass using a robust, but biased, approach...

  5. Thalamic neuron models encode stimulus information by burst-size modulation

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    Daniel Henry Elijah

    2015-09-01

    Full Text Available Thalamic neurons have been long assumed to fire in tonic mode during perceptive states, and in burst mode during sleep and unconsciousness. However, recent evidence suggests that bursts may also be relevant in the encoding of sensory information. Here we explore the neural code of such thalamic bursts. In order to assess whether the burst code is generic or whether it depends on the detailed properties of each bursting neuron, we analyzed two neuron models incorporating different levels of biological detail. One of the models contained no information of the biophysical processes entailed in spike generation, and described neuron activity at a phenomenological level. The second model represented the evolution of the individual ionic conductances involved in spiking and bursting, and required a large number of parameters. We analyzed the models' input selectivity using reverse correlation methods and information theory. We found that n-spike bursts from both models transmit information by modulating their spike count in response to changes to instantaneous input features, such as slope, phase, amplitude, etc. The stimulus feature that is most efficiently encoded by bursts, however, need not coincide with one of such classical features. We therefore searched for the optimal feature among all those that could be expressed as a linear transformation of the time-dependent input current. We found that bursting neurons transmitted 6 times more information about such more general features. The relevant events in the stimulus were located in a time window spanning ~100 ms before and ~20 ms after burst onset. Most importantly, the neural code employed by the simple and the biologically realistic models was largely the same, implying that the simple thalamic neuron model contains the essential ingredients that account for the computational properties of the thalamic burst code. Thus, our results suggest the n-spike burst code is a general property of

  6. Thalamic neuron models encode stimulus information by burst-size modulation.

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    Elijah, Daniel H; Samengo, Inés; Montemurro, Marcelo A

    2015-01-01

    Thalamic neurons have been long assumed to fire in tonic mode during perceptive states, and in burst mode during sleep and unconsciousness. However, recent evidence suggests that bursts may also be relevant in the encoding of sensory information. Here, we explore the neural code of such thalamic bursts. In order to assess whether the burst code is generic or whether it depends on the detailed properties of each bursting neuron, we analyzed two neuron models incorporating different levels of biological detail. One of the models contained no information of the biophysical processes entailed in spike generation, and described neuron activity at a phenomenological level. The second model represented the evolution of the individual ionic conductances involved in spiking and bursting, and required a large number of parameters. We analyzed the models' input selectivity using reverse correlation methods and information theory. We found that n-spike bursts from both models transmit information by modulating their spike count in response to changes to instantaneous input features, such as slope, phase, amplitude, etc. The stimulus feature that is most efficiently encoded by bursts, however, need not coincide with one of such classical features. We therefore searched for the optimal feature among all those that could be expressed as a linear transformation of the time-dependent input current. We found that bursting neurons transmitted 6 times more information about such more general features. The relevant events in the stimulus were located in a time window spanning ~100 ms before and ~20 ms after burst onset. Most importantly, the neural code employed by the simple and the biologically realistic models was largely the same, implying that the simple thalamic neuron model contains the essential ingredients that account for the computational properties of the thalamic burst code. Thus, our results suggest the n-spike burst code is a general property of thalamic neurons.

  7. Comparison of Midbrain and Thalamic Space-Specific Neurons in Barn Owls

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    Pérez, María Lucía; Peña, José Luis

    2008-01-01

    Spatial receptive fields of neurons in the auditory pathway of the barn owl result from the sensitivity to combinations of interaural time (ITD) and level differences across stimulus frequency. Both the forebrain and tectum of the owl contain such neurons. The neural pathways, which lead to the forebrain and tectal representations of auditory space, separate before the midbrain map of auditory space is synthesized. The first nuclei that belong exclusively to either the forebrain or the tectal pathways are the nucleus ovoidalis (Ov) and the external nucleus of the inferior colliculus (ICx), respectively. Both receive projections from the lateral shell subdivision of the inferior colliculus but are not interconnected. Previous studies indicate that the owl’s tectal representation of auditory space is different from those found in the owl’s forebrain and the mammalian brain. We addressed the question of whether the computation of spatial cues in both pathways is the same by comparing the ITD tuning of Ov and ICx neurons. Unlike in ICx, the relationship between frequency and ITD tuning had not been studied in single Ov units. In contrast to the conspicuous frequency independent ITD tuning of space-specific neurons of ICx, ITD selectivity varied with frequency in Ov. We also observed that the spatially tuned neurons of Ov respond to lower frequencies and are more broadly tuned to ITD than in ICx. Thus there are differences in the integration of frequency and ITD in the two sound-localization pathways. Thalamic neurons integrate spatial information not only within a broader frequency band but also across ITD channels. PMID:16424454

  8. Interactive Responses of a Thalamic Neuron to Formalin Induced Lasting Pain in Behaving Mice

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    Huh, Yeowool; Bhatt, Rushi; Jung, DaeHyun; Shin, Hee-sup; Cho, Jeiwon

    2012-01-01

    Thalamocortical (TC) neurons are known to relay incoming sensory information to the cortex via firing in tonic or burst mode. However, it is still unclear how respective firing modes of a single thalamic relay neuron contribute to pain perception under consciousness. Some studies report that bursting could increase pain in hyperalgesic conditions while others suggest the contrary. However, since previous studies were done under either neuropathic pain conditions or often under anesthesia, the mechanism of thalamic pain modulation under awake conditions is not well understood. We therefore characterized the thalamic firing patterns of behaving mice in response to nociceptive pain induced by inflammation. Our results demonstrated that nociceptive pain responses were positively correlated with tonic firing and negatively correlated with burst firing of individual TC neurons. Furthermore, burst properties such as intra-burst-interval (IntraBI) also turned out to be reliably correlated with the changes of nociceptive pain responses. In addition, brain stimulation experiments revealed that only bursts with specific bursting patterns could significantly abolish behavioral nociceptive responses. The results indicate that specific patterns of bursting activity in thalamocortical relay neurons play a critical role in controlling long-lasting inflammatory pain in awake and behaving mice. PMID:22292022

  9. Gap junctions in developing thalamic and neocortical neuronal networks

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    Niculescu, Dragos; Lohmann, C.

    2014-01-01

    The presence of direct, cytoplasmatic, communication between neurons in the brain of vertebrates has been demonstrated a long time ago. These gap junctions have been characterized in many brain areas in terms of subunit composition, biophysical properties, neuronal connectivity patterns, and

  10. Low-threshold Ca2+ current amplifies distal dendritic signaling in thalamic reticular neurons.

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    Crandall, Shane R; Govindaiah, G; Cox, Charles L

    2010-11-17

    The low-threshold transient calcium current (I(T)) plays a critical role in modulating the firing behavior of thalamic neurons; however, the role of I(T) in the integration of afferent information within the thalamus is virtually unknown. We have used two-photon laser scanning microscopy coupled with whole-cell recordings to examine calcium dynamics in the neurons of the strategically located thalamic reticular nucleus (TRN). We now report that a single somatic burst discharge evokes large-magnitude calcium responses, via I(T), in distal TRN dendrites. The magnitude of the burst-evoked calcium response was larger than those observed in thalamocortical projection neurons under the same conditions. We also demonstrate that direct stimulation of distal TRN dendrites, via focal glutamate application and synaptic activation, can locally activate distal I(T), producing a large distal calcium response independent of the soma/proximal dendrites. These findings strongly suggest that distally located I(T) may function to amplify afferent inputs. Boosting the magnitude ensures integration at the somatic level by compensating for attenuation that would normally occur attributable to passive cable properties. Considering the functional architecture of the TRN, elongated nature of their dendrites, and robust dendritic signaling, these distal dendrites could serve as sites of intense intra-modal/cross-modal integration and/or top-down modulation, leading to focused thalamocortical communication.

  11. Phencyclidine inhibits the activity of thalamic reticular gamma-aminobutyric acidergic neurons in rat brain.

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    Troyano-Rodriguez, Eva; Lladó-Pelfort, Laia; Santana, Noemi; Teruel-Martí, Vicent; Celada, Pau; Artigas, Francesc

    2014-12-15

    The neurobiological basis of action of noncompetitive N-methyl-D-aspartate acid receptor (NMDA-R) antagonists is poorly understood. Electrophysiological studies indicate that phencyclidine (PCP) markedly disrupts neuronal activity with an overall excitatory effect and reduces the power of low-frequency oscillations (LFO; <4 Hz) in thalamocortical networks. Because the reticular nucleus of the thalamus (RtN) provides tonic feed-forward inhibition to the rest of the thalamic nuclei, we examined the effect of PCP on RtN activity, under the working hypothesis that NMDA-R blockade in RtN would disinhibit thalamocortical networks. Drug effects (PCP followed by clozapine) on the activity of RtN (single unit and local field potential recordings) and prefrontal cortex (PFC; electrocorticogram) in anesthetized rats were assessed. PCP (.25-.5 mg/kg, intravenous) reduced the discharge rate of 19 of 21 RtN neurons to 37% of baseline (p < .000001) and the power of LFO in RtN and PFC to ~20% of baseline (p < .001). PCP also reduced the coherence between PFC and RtN in the LFO range. A low clozapine dose (1 mg/kg intravenous) significantly countered the effect of PCP on LFO in PFC but not in RtN and further reduced the discharge rate of RtN neurons. However, clozapine administration partly antagonized the fall in coherence and phase-locking values produced by PCP. PCP activates thalamocortical circuits in a bottom-up manner by reducing the activity of RtN neurons, which tonically inhibit thalamic relay neurons. However, clozapine reversal of PCP effects is not driven by restoring RtN activity and may involve a cortical action. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  12. Corticothalamic Synaptic Noise as a Mechanism for Selective Attention in Thalamic Neurons

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    Sébastien eBéhuret

    2015-12-01

    Full Text Available A reason why the thalamus is more than a passive gateway for sensory signals is that two-third of the synapses of thalamocortical neurons are directly or indirectly related to the activity of corticothalamic axons. While the responses of thalamocortical neurons evoked by sensory stimuli are well characterized, with ON- and OFF-center receptive field structures, the prevalence of synaptic noise resulting from neocortical feedback in intracellularly recorded thalamocortical neurons in vivo has attracted little attention. However, in vitro and modeling experiments point to its critical role for the integration of sensory signals. Here we combine our recent findings in a unified framework suggesting the hypothesis that corticothalamic synaptic activity is adapted to modulate the transfer efficiency of thalamocortical neurons during selective attention at three different levels: First, on ionic channels by interacting with intrinsic membrane properties, second at the neuron level by impacting on the input-output gain, and third even more effectively at the cell assembly level by boosting the information transfer of sensory features encoded in thalamic subnetworks. This top-down population control is achieved by tuning the correlations in subthreshold membrane potential fluctuations and is adapted to modulate the transfer of sensory features encoded by assemblies of thalamocortical relay neurons. We thus propose that cortically-controlled (de-correlation of subthreshold noise is an efficient and swift dynamic mechanism for selective attention in the thalamus.

  13. Tcf7l2 plays crucial roles in forebrain development through regulation of thalamic and habenular neuron identity and connectivity.

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    Lee, Myungsin; Yoon, Jiyeon; Song, Hobeom; Lee, Bumwhee; Lam, Duc Tri; Yoon, Jaeseung; Baek, Kwanghee; Clevers, Hans; Jeong, Yongsu

    2017-04-01

    The thalamus acts as a central integrator for processing and relaying sensory and motor information to and from the cerebral cortex, and the habenula plays pivotal roles in emotive decision making by modulating dopaminergic and serotonergic circuits. These neural compartments are derived from a common developmental progenitor domain, called prosomere 2, in the caudal forebrain. Thalamic and habenular neurons exhibit distinct molecular profile, neurochemical identity, and axonal circuitry. However, the mechanisms of how their progenitors in prosomere 2 give rise to these two populations of neurons and contribute to the forebrain circuitry remains unclear. In this study, we discovered a previously unrecognized role for Tcf7l2, a transcription factor known as the canonical Wnt nuclear effector and diabetes risk-conferring gene, in establishing neuronal identity and circuits of the caudal forebrain. Using genetic and chemical axon tracers, we showed that efferent axons of the thalamus, known as the thalamocortical axons (TCAs), failed to elongate normally and strayed from their normal course to inappropriate locations in the absence of Tcf7l2. Further experiments with thalamic explants revealed that the pathfinding defects of Tcf7l2-deficient TCAs were associated at least in part with downregulation of guidance receptors Robo1 and Robo2 expression. Moreover, the fasciculus retroflexus, the main habenular output tract, was missing in embryos lacking Tcf7l2. These axonal defects may result from dysregulation of Nrp2 guidance receptor. Strikingly, loss of Tcf7l2 caused a post-mitotic identity switch between thalamic and habenular neurons. Despite normal acquisition of progenitor identity in prosomere 2, Tcf7l2-deficient thalamic neurons adopted a molecular profile of a neighboring forebrain derivative, the habenula. Conversely, habenular neurons failed to maintain their normal post-mitotic neuronal identity and acquired a subset of thalamic neuronal features in the

  14. Discontinuous Galerkin finite element method for solving population density functions of cortical pyramidal and thalamic neuronal populations.

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    Huang, Chih-Hsu; Lin, Chou-Ching K; Ju, Ming-Shaung

    2015-02-01

    Compared with the Monte Carlo method, the population density method is efficient for modeling collective dynamics of neuronal populations in human brain. In this method, a population density function describes the probabilistic distribution of states of all neurons in the population and it is governed by a hyperbolic partial differential equation. In the past, the problem was mainly solved by using the finite difference method. In a previous study, a continuous Galerkin finite element method was found better than the finite difference method for solving the hyperbolic partial differential equation; however, the population density function often has discontinuity and both methods suffer from a numerical stability problem. The goal of this study is to improve the numerical stability of the solution using discontinuous Galerkin finite element method. To test the performance of the new approach, interaction of a population of cortical pyramidal neurons and a population of thalamic neurons was simulated. The numerical results showed good agreement between results of discontinuous Galerkin finite element and Monte Carlo methods. The convergence and accuracy of the solutions are excellent. The numerical stability problem could be resolved using the discontinuous Galerkin finite element method which has total-variation-diminishing property. The efficient approach will be employed to simulate the electroencephalogram or dynamics of thalamocortical network which involves three populations, namely, thalamic reticular neurons, thalamocortical neurons and cortical pyramidal neurons. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Fear conditioning leads to alteration in specific genes expression in cortical and thalamic neurons that project to the lateral amygdala.

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    Katz, Ira K; Lamprecht, Raphael

    2015-02-01

    RNA transcription is needed for memory formation. However, the ability to identify genes whose expression is altered by learning is greatly impaired because of methodological difficulties in profiling gene expression in specific neurons involved in memory formation. Here, we report a novel approach to monitor the expression of genes after learning in neurons in specific brain pathways needed for memory formation. In this study, we aimed to monitor gene expression after fear learning. We retrogradely labeled discrete thalamic neurons that project to the lateral amygdala (LA) of rats. The labeled neurons were dissected, using laser microdissection microscopy, after fear conditioning learning or unpaired training. The RNAs from the dissected neurons were subjected to microarray analysis. The levels of selected RNAs detected by the microarray analysis to be altered by fear conditioning were also assessed by nanostring analysis. We observed that the expression of genes involved in the regulation of translation, maturation and degradation of proteins was increased 6 h after fear conditioning compared to unpaired or naïve trained rats. These genes were not expressed 24 h after training or in cortical neurons that project to the LA. The expression of genes involved in transcription regulation and neuronal development was altered after fear conditioning learning in the cortical-LA pathway. The present study provides key information on the identity of genes expressed in discrete thalamic and cortical neurons that project to the LA after fear conditioning. Such an approach could also serve to identify gene products as targets for the development of a new generation of therapeutic agents that could be aimed to functionally identified brain circuits to treat memory-related disorders. © 2014 International Society for Neurochemistry.

  16. Effects of intravenous metamizole on ongoing and evoked activity of dura-sensitive thalamic neurons in rats.

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    Sokolov, Alexey Y; Lyubashina, Olga A; Sivachenko, Ivan B; Panteleev, Sergey S

    2014-05-15

    Migraine and tension-type headache (TTH) are the most common forms of primary headaches. A general key mechanism underlying development of both the diseases is the trigeminal system activation associated with the ascending nociceptive transmission via the trigemino-thalamo-cortical pathway. The ventroposteromedial (VPM) nucleus is a key thalamic structure, receiving afferent inflow from the craniofacial region; it holds the third-order neurons responsible for conveying sensory information from the extra- and intracranial nociceptors to the cortex. The VPM is currently seen as a therapeutic target for various antimigraine medications, which is shown to reduce the VPM neuronal excitability. A non-opioid analgesic metamizole is widely used in some countries for acute treatment of migraine or TTH. However, the precise mechanisms underlying anticephalgic action of metamizole remain unclear. The objective of our study performed in the rat model of trigemino-durovascular nociception was to evaluate the effects of intravenously administered metamizole on ongoing and evoked firing of the dura-sensitive VPM neurons. The experiments were carried out on rats under urethane-chloralose anesthesia. Cumulative administration of metamizole (thrice-repeated intravenous infusion of 150 mg/kg performed 30 min apart) in 56% of cases produced a suppression of both the ongoing activity of the thalamic VPM neurons and their responses to dural electrical stimulation. Although the inhibitory effect was prevailing, a number of VPM neurons were indifferent to the administration of metamizole. These data suggest that one of the main components of neural mechanism underlying anticephalgic action of metamizole is suppression of the thalamo-cortical nociceptive transmission associated with trigemino-vascular activation. Copyright © 2014 Elsevier B.V. All rights reserved.

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

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    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.

  18. Individual mediodorsal thalamic neurons project to multiple areas of the rat prefrontal cortex: A single neuron-tracing study using virus vectors.

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    Kuramoto, Eriko; Pan, Shixiu; Furuta, Takahiro; Tanaka, Yasuhiro R; Iwai, Haruki; Yamanaka, Atsushi; Ohno, Sachi; Kaneko, Takeshi; Goto, Tetsuya; Hioki, Hiroyuki

    2017-01-01

    The prefrontal cortex has an important role in a variety of cognitive and executive processes, and is generally defined by its reciprocal connections with the mediodorsal thalamic nucleus (MD). The rat MD is mainly subdivided into three segments, the medial (MDm), central (MDc), and lateral (MDl) divisions, on the basis of the cytoarchitecture and chemoarchitecture. The MD segments are known to topographically project to multiple prefrontal areas at the population level: the MDm mainly to the prelimbic, infralimbic, and agranular insular areas; the MDc to the orbital and agranular insular areas; and the MDl to the prelimbic and anterior cingulate areas. However, it is unknown whether individual MD neurons project to single or multiple prefrontal cortical areas. In the present study, we visualized individual MD neurons with Sindbis virus vectors, and reconstructed whole structures of MD neurons. While the main cortical projection targets of MDm, MDc, and MDl neurons were generally consistent with those of previous results, it was found that individual MD neurons sent their axon fibers to multiple prefrontal areas, and displayed various projection patterns in the target areas. Furthermore, the axons of single MD neurons were not homogeneously spread, but were rather distributed to form patchy axon arbors approximately 1 mm in diameter. The multiple-area projections and patchy axon arbors of single MD neurons might be able to coactivate cortical neuron groups in distant prefrontal areas simultaneously. Furthermore, considerable heterogeneity of the projection patterns is likely, to recruit the different sets of cortical neurons, and thus contributes to a variety of prefrontal functions. J. Comp. Neurol. 525:166-185, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. The calcium-binding protein parvalbumin modulates the firing 1 properties of the reticular thalamic nucleus bursting neurons.

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    Albéri, Lavinia; Lintas, Alessandra; Kretz, Robert; Schwaller, Beat; Villa, Alessandro E P

    2013-06-01

    The reticular thalamic nucleus (RTN) of the mouse is characterized by an overwhelming majority of GABAergic neurons receiving afferences from both the thalamus and the cerebral cortex and sending projections mainly on thalamocortical neurons. The RTN neurons express high levels of the "slow Ca(2+) buffer" parvalbumin (PV) and are characterized by low-threshold Ca(2+) currents, I(T). We performed extracellular recordings in ketamine/xylazine anesthetized mice in the rostromedial portion of the RTN. In the RTN of wild-type and PV knockout (PVKO) mice we distinguished four types of neurons characterized on the basis of their firing pattern: irregular firing (type I), medium bursting (type II), long bursting (type III), and tonically firing (type IV). Compared with wild-type mice, we observed in the PVKOs the medium bursting (type II) more frequently than the long bursting type and longer interspike intervals within the burst without affecting the number of spikes. This suggests that PV may affect the firing properties of RTN neurons via a mechanism associated with the kinetics of burst discharges. Ca(v)3.2 channels, which mediate the I(T) currents, were more localized to the somatic plasma membrane of RTN neurons in PVKO mice, whereas Ca(v)3.3 expression was similar in both genotypes. The immunoelectron microscopy analysis showed that Ca(v)3.2 channels were localized at active axosomatic synapses, thus suggesting that the differential localization of Ca(v)3.2 in the PVKOs may affect bursting dynamics. Cross-correlation analysis of simultaneously recorded neurons from the same electrode tip showed that about one-third of the cell pairs tended to fire synchronously in both genotypes, independent of PV expression. In summary, PV deficiency does not affect the functional connectivity between RTN neurons but affects the distribution of Ca(v)3.2 channels and the dynamics of burst discharges of RTN cells, which in turn regulate the activity in the thalamocortical circuit.

  20. Resolving the detailed structure of cortical and thalamic neurons in the adult rat brain with refined biotinylated dextran amine labeling.

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    Changying Ling

    Full Text Available Biotinylated dextran amine (BDA has been used frequently for both anterograde and retrograde pathway tracing in the central nervous system. Typically, BDA labels axons and cell somas in sufficient detail to identify their topographical location accurately. However, BDA labeling often has proved to be inadequate to resolve the fine structural details of axon arbors or the dendrites of neurons at a distance from the site of BDA injection. To overcome this limitation, we varied several experimental parameters associated with the BDA labeling of neurons in the adult rat brain in order to improve the sensitivity of the method. Specifically, we compared the effect on labeling sensitivity of: (a using 3,000 or 10,000 MW BDA; (b injecting different volumes of BDA; (c co-injecting BDA with NMDA; and (d employing various post-injection survival times. Following the extracellular injection of BDA into the visual cortex, labeled cells and axons were observed in both cortical and thalamic areas of all animals studied. However, the detailed morphology of axon arbors and distal dendrites was evident only under optimal conditions for BDA labeling that take into account the: molecular weight of the BDA used, concentration and volume of BDA injected, post-injection survival time, and toning of the resolved BDA with gold and silver. In these instances, anterogradely labeled axons and retrogradely labeled dendrites were resolved in fine detail, approximating that which can be achieved with intracellularly injected compounds such as biocytin or fluorescent dyes.

  1. CACNA1H missense mutations associated with amyotrophic lateral sclerosis alter Cav3.2 T-type calcium channel activity and reticular thalamic neuron firing.

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    Rzhepetskyy, Yuriy; Lazniewska, Joanna; Blesneac, Iulia; Pamphlett, Roger; Weiss, Norbert

    2016-11-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. In a recent study by Steinberg and colleagues, 2 recessive missense mutations were identified in the Cav3.2 T-type calcium channel gene (CACNA1H), in a family with an affected proband (early onset, long duration ALS) and 2 unaffected parents. We have introduced and functionally characterized these mutations using transiently expressed human Cav3.2 channels in tsA-201 cells. Both of these mutations produced mild but significant changes on T-type channel activity that are consistent with a loss of channel function. Computer modeling in thalamic reticular neurons suggested that these mutations result in decreased neuronal excitability of thalamic structures. Taken together, these findings implicate CACNA1H as a susceptibility gene in amyotrophic lateral sclerosis.

  2. Morphology and electrophysiological properties of reticularis thalami neurons in cat: in vivo study of a thalamic pacemaker.

    Science.gov (United States)

    Mulle, C; Madariaga, A; Deschênes, M

    1986-08-01

    Reticularis thalami neurons (RE neurons) were identified morphologically, and their electrophysiological properties were studied in cat under barbiturate anesthesia. Intracellular HRP injections showed that RE neurons possessed very long dendrites bearing numerous filopodia-like appendages and that their axons were directed toward main thalamic nuclei. As a rule, small axonal branches were also emitted within the RE nucleus itself. At rest, the membrane potential of RE neurons displayed 2 types of oscillations: a slow 0.1-0.2 Hz oscillation and fast 7-12 Hz oscillations occurring on the positive phase of the former. Episodes of spindle (7-12 Hz) waves lasted for 2-3 sec and were characterized by rhythmic depolarizations and burst discharges. Intracellular injections of QX314 and current pulse analyses revealed the presence in RE cells of 2 distinct inward currents: a persistent current that promoted tonic firing and a low-threshold current deinactivated by hyperpolarization that generated burst discharges. The low-threshold current deinactivated with large somatic hyperpolarizations (up to 30 mV) and produced depolarizing responses that lasted for about 70 msec. In addition, low-threshold responses appeared rhythmically at intervals of about 150 msec after recovery of the membrane potential from hyperpolarization. Because of their duration, voltage dependence, and persistence after intracellular injections of QX314, it is suggested that these responses resulted from activation of a low-threshold Ca2+ current at the dendritic level. In QX314-injected cells, selective components of spontaneous oscillations were abolished, among them the positive phase of the slow oscillation and late depolarizing humps that followed burst discharges within spindle sequences. However, the rhythmic occurrence of spindle episodes at 0.1-0.2 Hz was never affected by DC currents or by QX314 or Cl- injections, suggesting that oscillations within a particular RE neuron partly reflected the

  3. Slow fluctuations of single unit activities of hippocampal and thalamic neurons in cats. I. Relation to natural sleep and alert states.

    Science.gov (United States)

    Kodama, T; Mushiake, H; Shima, K; Nakahama, H; Yamamoto, M

    1989-05-15

    Spontaneous unit discharges during the natural sleep-wakefulness cycle in two different neuronal groups, the hippocampal pyramidal cells and thalamic ventrobasal neurons, have been analyzed. The results show that both neurons fire with white-noise-like fluctuations during the slow-wave sleep, and with slow fluctuations with power spectral densities inversely proportional to the frequency in the frequency range of 0.02-1.0 Hz, during the paradoxical sleep. This confirms that the characteristics of fluctuations in neuronal activities of the mesencephalic reticular formation observed in our previous study are more general phenomena in the cat's brain. Partly similar behavior of spectral densities is also observed during the alert state. These observations are quantitatively confirmed by the statistical time series analysis of the spike density processes of spontaneous activities.

  4. Is state-dependent alternation of slow dynamics in central single neurons during sleep present in the rat ventroposterior thalamic nucleus?

    Science.gov (United States)

    Takahashi, Kazumi; Koyama, Yoshimasa; Kayama, Yukihiko; Nakamura, Kazuhiro; Yamamoto, Mitsuaki

    2004-02-01

    Based upon our previous results in cats, we hypothesized that neurons in the central processor systems of the brain generally exhibit state-dependent dynamics alternation of slow fluctuations in spontaneous activity during sleep. To test the validity of this hypothesis across species, we recorded single neuronal activity during sleep from the ventroposterior (VP) thalamic nucleus in unanesthetized, head-restrained rats. Spectral analysis was performed on successive spike-counts of neuronal activity recorded during three stages of the sleep-wakefulness cycle: wakefulness (W, n=6), slow-wave sleep (SWS, n=20), and paradoxical sleep (PS, n=32). We found that firing of VP neurons displayed white-noise-like dynamics over the range of 0.04-1.0 Hz during SWS and 1/f-noise-like dynamics over the same range during PS. We also demonstrated for the first time that the slow dynamics of neuronal activity during quiet wakefulness (but not drowsiness) are white-noise-like. These results suggest that our hypothesis is true across species. During W and SWS, the brain may be considered as under global inhibition. Conversely, PS may represent a state of global disinhibition in the brain, where neuronal activity exhibits 1/f-noise-like dynamics. Fluctuations observed in living organisms may be involved in essential processes in generation and function of sleep states.

  5. Self-sustained asynchronous irregular states and Up-Down states in thalamic, cortical and thalamocortical networks of nonlinear integrate-and-fire neurons.

    Science.gov (United States)

    Destexhe, Alain

    2009-12-01

    Randomly-connected networks of integrate-and-fire (IF) neurons are known to display asynchronous irregular (AI) activity states, which resemble the discharge activity recorded in the cerebral cortex of awake animals. However, it is not clear whether such activity states are specific to simple IF models, or if they also exist in networks where neurons are endowed with complex intrinsic properties similar to electrophysiological measurements. Here, we investigate the occurrence of AI states in networks of nonlinear IF neurons, such as the adaptive exponential IF (Brette-Gerstner-Izhikevich) model. This model can display intrinsic properties such as low-threshold spike (LTS), regular spiking (RS) or fast-spiking (FS). We successively investigate the oscillatory and AI dynamics of thalamic, cortical and thalamocortical networks using such models. AI states can be found in each case, sometimes with surprisingly small network size of the order of a few tens of neurons. We show that the presence of LTS neurons in cortex or in thalamus, explains the robust emergence of AI states for relatively small network sizes. Finally, we investigate the role of spike-frequency adaptation (SFA). In cortical networks with strong SFA in RS cells, the AI state is transient, but when SFA is reduced, AI states can be self-sustained for long times. In thalamocortical networks, AI states are found when the cortex is itself in an AI state, but with strong SFA, the thalamocortical network displays Up and Down state transitions, similar to intracellular recordings during slow-wave sleep or anesthesia. Self-sustained Up and Down states could also be generated by two-layer cortical networks with LTS cells. These models suggest that intrinsic properties such as adaptation and low-threshold bursting activity are crucial for the genesis and control of AI states in thalamocortical networks.

  6. L-type calcium channels and MAP kinase contribute to thyrotropin-releasing hormone-induced depolarization in thalamic paraventricular nucleus neurons.

    Science.gov (United States)

    Kolaj, Miloslav; Zhang, Li; Renaud, Leo P

    2016-06-01

    In rat paraventricular thalamic nucleus (PVT) neurons, activation of thyrotropin-releasing hormone (TRH) receptors enhances neuronal excitability via concurrent decrease in a G protein-coupled inwardly rectifying K (GIRK)-like conductance and opening of a cannabinoid receptor-sensitive transient receptor potential canonical (TRPC)-like conductance. Here, we investigated the calcium (Ca(2+)) contribution to the components of this TRH-induced response. TRH-induced membrane depolarization was reduced in the presence of intracellular BAPTA, also in media containing nominally zero [Ca(2+)]o, suggesting a critical role for both intracellular Ca(2+) release and Ca(2+) influx. TRH-induced inward current was unchanged by T-type Ca(2+) channel blockade, but was decreased by blockade of high-voltage-activated Ca(2+) channels (HVACCs). Both the pharmacologically isolated GIRK-like and the TRPC-like components of the TRH-induced response were decreased by nifedipine and increased by BayK8644, implying Ca(2+) influx via L-type Ca(2+) channels. Only the TRPC-like conductance was reduced by either thapsigargin or dantrolene, suggesting a role for ryanodine receptors and Ca(2+)-induced Ca(2+) release in this component of the TRH-induced response. In pituitary and other cell lines, TRH stimulates MAPK. In PVT neurons, only the GIRK-like component of the TRH-induced current was selectively decreased in the presence of PD98059, a MAPK inhibitor. Collectively, the data imply that TRH-induced depolarization and inward current in PVT neurons involve both a dependency on extracellular Ca(2+) influx via opening of L-type Ca(2+) channels, a sensitivity of a TRPC-like component to intracellular Ca(2+) release via ryanodine channels, and a modulation by MAPK of a GIRK-like conductance component. Copyright © 2016 the American Physiological Society.

  7. A novel single-cell staining procedure performed in vivo under electrophysiological control: morpho-functional features of juxtacellularly labeled thalamic cells and other central neurons with biocytin or Neurobiotin.

    Science.gov (United States)

    Pinault, D

    1996-04-01

    We describe a novel and very effective single-cell labeling method with unique advantages for revealing the axonal and dendritic fields of any extracellularly recorded neuron. This procedure involves the use of fine glass micro-pipettes (tip diameter: approximately 1 micron), which contain biocytin or Neurobiotin dissolved in a salt solution, for the simultaneous juxtacellular recording and tracer iontophoresis. Once a neuron is well-isolated and identified, low intensity ( 86%) far exceeds that obtained by direct intracellular injections of tracers as shown by the labeling of a large sample of 100 individual cells (from 115 attempts) in the thalamic reticular (Rt) nucleus of 33 rats. We thereby demonstrate that Rt cells project to restricted regions of a single thalamic nucleus, including anterior thalamic nuclei, and that the thalamus and Rt complex have reciprocal connections. The juxtacellular procedure thus represents an ideal directed single-cell labeling tool for determination of functional properties, for subsequent identification, for delineation of overall neuronal architecture and for tracing neuronal pathways, provided care is taken to avoid the possible drawbacks and pitfalls that are illustrated and discussed in the present paper.

  8. Promotion of non-rapid eye movement sleep and activation of reticular thalamic neurons by a novel MT2 melatonin receptor ligand.

    Science.gov (United States)

    Ochoa-Sanchez, Rafael; Comai, Stefano; Lacoste, Baptiste; Bambico, Francis Rodriguez; Dominguez-Lopez, Sergio; Spadoni, Gilberto; Rivara, Silvia; Bedini, Annalida; Angeloni, Debora; Fraschini, Franco; Mor, Marco; Tarzia, Giorgio; Descarries, Laurent; Gobbi, Gabriella

    2011-12-14

    Melatonin activates two brain G-protein coupled receptors, MT(1) and MT(2), whose differential roles in the sleep-wake cycle remain to be defined. The novel MT(2) receptor partial agonist, N-{2-[(3-methoxyphenyl) phenylamino] ethyl} acetamide (UCM765), is here shown to selectively promote non-rapid eye movement sleep (NREMS) in rats and mice. The enhancement of NREMS by UCM765 is nullified by the pharmacological blockade or genetic deletion of MT(2) receptors. MT(2), but not MT(1), knock-out mice show a decrease in NREMS compared to the wild strain. Immunohistochemical labeling reveals that MT(2) receptors are localized in sleep-related brain regions, and notably the reticular thalamic nucleus (Rt). Microinfusion of UCM765 in the Rt promotes NREMS, and its systemic administration induces an increase in firing and rhythmic burst activity of Rt neurons, which is blocked by the MT(2) antagonist 4-phenyl-2-propionamidotetralin. Since developing hypnotics that increase NREMS without altering sleep architecture remains a medical challenge, MT(2) receptors may represent a novel target for the treatment of sleep disorders.

  9. Thalamic hemorrhage. A prospective study of 100 patients.

    Science.gov (United States)

    Kumral, E; Kocaer, T; Ertübey, N O; Kumral, K

    1995-06-01

    The clinical features of thalamic hemorrhage in terms of localization are of great interest in many studies. To better understand the relationship between the localization of thalamic hemorrhage and clinical features. we evaluated the characteristics of patients with four different topographic types of thalamic hemorrhage. We prospectively studied 100 patients with thalamic hemorrhage who were admitted consecutively to our primary care unit. We divided them into two groups according to large (> 2 cm in diameter and/or > 4 mL in volume) and small thalamic hemorrhage. Four topographic subgroups (large and small) were compared to identify clinical syndromes associated with distinct lesion locations. All patients with posterolateral thalamic hemorrhage had severe sensorimotor deficit. Neuropsychological disturbances in patients with posterolateral thalamic hemorrhage were prominent, with primarily transcortical aphasia in those with left-sided lesions and hemineglect and anosognosia in those with right-sided lesions. Several variants of vertical gaze dysfunction, skew ocular deviation, gaze preference toward the site of the lesion, and miotic pupils were frequent in posterolateral thalamic hemorrhage, particularly in the large type. Patients with small and large anterolateral thalamic hemorrhage were characterized by severe motor and sensory deficits; language and oculomotor disturbances were also observed, although less frequently than in posterolateral hemorrhage. Sensorimotor deficits were observed in patients with medial thalamic hemorrhage (moderate in small hemorrhages and severe in large hemorrhages because of involvement of the adjacent internal capsule). Language disturbances in patients with left-sided lesions and neglect in patients with right-sided lesions were seen only in large medial thalamic hemorrhage. Dorsal thalamic hemorrhage was rare and characterized by mild and transient sensorimotor disturbances. Among patients with dorsal thalamic hemorrhages

  10. Thalamic alexia with agraphia

    Directory of Open Access Journals (Sweden)

    Fábio Henrique de Gobbi Porto

    2012-02-01

    Full Text Available Alexia with agraphia is defined as an acquired impairment affecting reading and writing ability. It can be associated with aphasia, but can also occur as an isolated entity. This impairment has classically been associated with a left angular gyrus lesion In the present study, we describe a case involving a patient who developed alexia with agraphia and other cognitive deficits after a thalamic hemorrhage. In addition, we discuss potential mechanisms of this cortical dysfunction syndrome caused by subcortical injury. We examined a patient who presented with alexia with agraphia and other cognitive deficits due to a hemorrhage in the left thalamus. Neuropsychological evaluation showed attention, executive function, arithmetic and memory impairments. In addition, language tests revealed severe alexia with agraphia in the absence of aphasia. Imaging studies disclosed an old thalamic hemorrhage involving the anterior, dorsomedial and pulvinar nuclei. Tractography revealed asymmetric thalamocortical radiations in the parietal region (left - right, and single photon emission computed tomography demonstrated hypoperfusion in the left thalamus that extended to the frontal and parietal cortices. Cortical cognitive deficits, including alexia with agraphia, may occur as the result of thalamic lesions. The probable mechanism is a diaschisis phenomenon involving thalamic tract disconnections.

  11. Thalamic semantic paralexia

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    Michael Hoffmann

    2012-03-01

    Full Text Available Alexia may be divided into different subtypes, with semantic paralexia being particularly rare. A 57 year old woman with a discreet left thalamic stroke and semantic paralexia is described. Language evalution with the Boston Diagnostic Aphasia Battery confirmed the semantic paralexia (deep alexia. Multimodality magnetic resonance imaging brain scanning excluded other cerebral lesions. A good recovery ensued.

  12. Thalamic physiology of intentional essential tremor is more like cerebellar tremor than postural essential tremor

    OpenAIRE

    Zakaria, R; Lenz, FA; Hua, S; Avin, BH; Liu, CC; Mari, Z

    2013-01-01

    The neuronal physiological correlates of clinical heterogeneity in human essential tremor are unknown. We now test the hypothesis that thalamic neuronal and EMG activities during intention essential tremor are similar to those of the intention tremor which is characteristic of cerebellar lesions. Thalamic neuronal firing was studied in a cerebellar relay nucleus (ventral intermediate, Vim) and in a pallidal relay nucleus (ventral oral posterior, Vop) during stereotactic surgery for the treatm...

  13. ELECTROPHYSIOLOGICAL CHARACTERISTICS OF PARAVENTRICULAR THALAMIC (PVT NEURONS IN RESPONSE TO CHRONIC COCAINE EXPOSURE: EFFECTS OF COCAINE- AND AMPHETAMINE-REGULATED TRANSCRIPT (CART

    Directory of Open Access Journals (Sweden)

    Jiann Wei eYeoh

    2014-08-01

    Full Text Available Recent work has established that the paraventricular thalamus (PVT is a central node in the brain reward-seeking pathway. This role is likely mediated in part through the dense projections to the PVT from hypothalamic peptide transmitter systems such as orexin, and cocaine- and amphetamine-regulated transcript (CART, both of which play key roles in drug-seeking behaviour. Consistent with this proposition, we previously found that inactivation of the PVT or infusions of CART into the PVT suppressed drug-seeking behaviour in an animal model of contingent cocaine self-administration. Despite this work, very few studies have assessed the basic physiological properties of PVT neurons and how these parameters are altered by exposure to drugs such as cocaine. We set out to address these questions by employing an electrophysiological approach to record from anterior PVT (aPVT neurons from cocaine-treated and control animals. First, we determined the excitability of aPVT neurons by injecting a series of depolarizing current steps and characterizing the resulting action potential (AP discharge properties. Second, we investigated the effects of CART on excitatory synaptic inputs to aPVT neurons. We found that the majority of aPVT neurons exhibited tonic firing (TF, and initial bursting (IB consistent with previous studies. However, we also identified PVT neurons that exhibited delayed firing (DF, single spiking (SS and reluctant firing (RF. Interestingly, cocaine exposure shifted the proportion of aPVT neurons that exhibited TF. Further, application of CART suppressed excitatory synaptic drive to PVT. This finding is consistent with our previous behavioural data, which showed that CART signaling in the PVT negatively regulates drug-seeking behaviour. Together, these studies support previous anatomical evidence that the PVT can integrate reward-relevant information and provides a putative mechanism through which drugs of abuse can dysregulate this system in

  14. T-type calcium channels cause bursts of spikes in motor but not sensory thalamic neurons during mimicry of natural patterns of synaptic input

    Science.gov (United States)

    Kim, Haram R.; Hong, Su Z.; Fiorillo, Christopher D.

    2015-01-01

    Although neurons within intact nervous systems can be classified as ‘sensory’ or ‘motor,’ it is not known whether there is any general distinction between sensory and motor neurons at the cellular or molecular levels. Here, we extend and test a theory according to which activation of certain subtypes of voltage-gated ion channel (VGC) generate patterns of spikes in neurons of motor systems, whereas VGC are proposed to counteract patterns in sensory neurons. We previously reported experimental evidence for the theory from visual thalamus, where we found that T-type calcium channels (TtCCs) did not cause bursts of spikes but instead served the function of ‘predictive homeostasis’ to maximize the causal and informational link between retinogeniculate excitation and spike output. Here, we have recorded neurons in brain slices from eight sensory and motor regions of rat thalamus while mimicking key features of natural excitatory and inhibitory post-synaptic potentials. As predicted by theory, TtCC did cause bursts of spikes in motor thalamus. TtCC-mediated responses in motor thalamus were activated at more hyperpolarized potentials and caused larger depolarizations with more spikes than in visual and auditory thalamus. Somatosensory thalamus is known to be more closely connected to motor regions relative to auditory and visual thalamus, and likewise the strength of its TtCC responses was intermediate between these regions and motor thalamus. We also observed lower input resistance, as well as limited evidence of stronger hyperpolarization-induced (‘H-type’) depolarization, in nuclei closer to motor output. These findings support our theory of a specific difference between sensory and motor neurons at the cellular level. PMID:26582654

  15. T-type calcium channels cause bursts of spikes in motor but not sensory thalamic neurons during mimicry of natural patterns of synaptic input.

    Science.gov (United States)

    Kim, Haram R; Hong, Su Z; Fiorillo, Christopher D

    2015-01-01

    Although neurons within intact nervous systems can be classified as 'sensory' or 'motor,' it is not known whether there is any general distinction between sensory and motor neurons at the cellular or molecular levels. Here, we extend and test a theory according to which activation of certain subtypes of voltage-gated ion channel (VGC) generate patterns of spikes in neurons of motor systems, whereas VGC are proposed to counteract patterns in sensory neurons. We previously reported experimental evidence for the theory from visual thalamus, where we found that T-type calcium channels (TtCCs) did not cause bursts of spikes but instead served the function of 'predictive homeostasis' to maximize the causal and informational link between retinogeniculate excitation and spike output. Here, we have recorded neurons in brain slices from eight sensory and motor regions of rat thalamus while mimicking key features of natural excitatory and inhibitory post-synaptic potentials. As predicted by theory, TtCC did cause bursts of spikes in motor thalamus. TtCC-mediated responses in motor thalamus were activated at more hyperpolarized potentials and caused larger depolarizations with more spikes than in visual and auditory thalamus. Somatosensory thalamus is known to be more closely connected to motor regions relative to auditory and visual thalamus, and likewise the strength of its TtCC responses was intermediate between these regions and motor thalamus. We also observed lower input resistance, as well as limited evidence of stronger hyperpolarization-induced ('H-type') depolarization, in nuclei closer to motor output. These findings support our theory of a specific difference between sensory and motor neurons at the cellular level.

  16. Broca's area - thalamic connectivity.

    Science.gov (United States)

    Bohsali, Anastasia A; Triplett, William; Sudhyadhom, Atchar; Gullett, Joseph M; McGregor, Keith; FitzGerald, David B; Mareci, Thomas; White, Keith; Crosson, Bruce

    2015-02-01

    Broca's area is crucially involved in language processing. The sub-regions of Broca's area (pars triangularis, pars opercularis) presumably are connected via corticocortical pathways. However, growing evidence suggests that the thalamus may also be involved in language and share some of the linguistic functions supported by Broca's area. Functional connectivity is thought to be achieved via corticothalamic/thalamocortical white matter pathways. Our study investigates structural connectivity between Broca's area and the thalamus, specifically ventral anterior nucleus and pulvinar. We demonstrate that Broca's area shares direct connections with these thalamic nuclei and suggest a local Broca's area-thalamus network potentially involved in linguistic processing. Thalamic connectivity with Broca's area may serve to selectively recruit cortical regions storing multimodal features of lexical items and to bind them together during lexical-semantic processing. In addition, Broca's area-thalamic circuitry may enable cortico-thalamo-cortical information transfer and modulation between BA 44 and 45 during language comprehension and production. Published by Elsevier Inc.

  17. Thalamic Lesions: A Radiological Review

    Directory of Open Access Journals (Sweden)

    Dimitri Renard

    2014-01-01

    Full Text Available Background. Thalamic lesions are seen in a multitude of disorders including vascular diseases, metabolic disorders, inflammatory diseases, trauma, tumours, and infections. In some diseases, thalamic involvement is typical and sometimes isolated, while in other diseases thalamic lesions are observed only occasionally (often in the presence of other typical extrathalamic lesions. Summary. In this review, we will mainly discuss the MRI characteristics of thalamic lesions. Identification of the origin of the thalamic lesion depends on the exact localisation inside the thalamus, the presence of extrathalamic lesions, the signal changes on different MRI sequences, the evolution of the radiological abnormalities over time, the history and clinical state of the patient, and other radiological and nonradiological examinations.

  18. Thalamic activity and biochemical changes in individuals with neuropathic pain following spinal cord injury

    Science.gov (United States)

    Gustin, S.M.; Wrigley, P.J.; Youssef, A.M.; McIndoe, L.; Wilcox, S.L.; Rae, C.D.; Edden, R; Siddall, P.J.; Henderson, L.A.

    2015-01-01

    There is increasing evidence relating thalamic changes to the generation and/or maintenance of neuropathic pain. We have recently reported that neuropathic orofacial pain is associated with altered thalamic anatomy, biochemistry and activity, which may result in disturbed thalamocortical oscillatory circuits. Despite this evidence, it is possible that these thalamic changes are not responsible for the presence of pain per se, but result as a consequence of the injury. To clarify this subject, we compared brain activity and biochemistry in 12 people with below-level neuropathic pain after complete thoracic spinal cord injury to 11 people with similar injuries and no neuropathic pain and 21 age and gender matched healthy controls. Quantitative arterial spinal labelling was used to measure thalamic activity and magnetic resonance spectroscopy was used to determine changes in neuronal variability quantifying N-acetylaspartate and alterations in inhibitory function quantifying gamma amino butyric acid. This study revealed that the presence of neuropathic pain is associated with significant changes in thalamic biochemistry and neuronal activity. More specifically, the presence of neuropathic pain following spinal cord injury is associated with significant reductions in thalamic N-acetylaspartate, gamma amino butyric acid content and blood flow in the region of the thalamic reticular nucleus. Spinal cord injury on its own did not account for these changes. These findings support the hypothesis that neuropathic pain is associated with altered thalamic structure and function, which may disturb central processing and play a key role in the experience of neuropathic pain. PMID:24530612

  19. Thalamic noradrenaline in Parkinson's disease: deficits suggest role in motor and non-motor symptoms.

    Science.gov (United States)

    Pifl, Christian; Kish, Stephen J; Hornykiewicz, Oleh

    2012-11-01

    The thalamus occupies a pivotal position within the corticobasal ganglia-cortical circuits. In Parkinson's disease (PD), the thalamus exhibits pathological neuronal discharge patterns, foremost increased bursting and oscillatory activity, which are thought to perturb the faithful transfer of basal ganglia impulse flow to the cortex. Analogous abnormal thalamic discharge patterns develop in animals with experimentally reduced thalamic noradrenaline; conversely, added to thalamic neuronal preparations, noradrenaline exhibits marked antioscillatory and antibursting activity. Our study is based on this experimentally established link between noradrenaline and the quality of thalamic neuronal discharges. We analyzed 14 thalamic nuclei from all functionally relevant territories of 9 patients with PD and 8 controls, and measured noradrenaline with high-performance liquid chromatography with electrochemical detection. In PD, noradrenaline was profoundly reduced in all nuclei of the motor (pallidonigral and cerebellar) thalamus (ventroanterior: -86%, P = .0011; ventrolateral oral: -87%, P = .0010; ventrolateral caudal: -89%, P = .0014): Also, marked noradrenaline losses, ranging from 68% to 91% of controls, were found in other thalamic territories, including associative, limbic and intralaminar regions; the primary sensory regions were only mildly affected. The marked noradrenergic deafferentiation of the thalamus discloses a strategically located noradrenergic component in the overall pathophysiology of PD, suggesting a role in the complex mechanisms involved with the genesis of the motor and non-motor symptoms. Our study thus significantly contributes to the knowledge of the extrastriatal nondopaminergic mechanisms of PD with direct relevance to treatment of this disorder. Copyright © 2012 Movement Disorder Society.

  20. Thalamic mechanisms in language: a reconsideration based on recent findings and concepts.

    Science.gov (United States)

    Crosson, Bruce

    2013-07-01

    Recent literature on thalamic aphasia and thalamic activity during neuroimaging is selectively reviewed followed by a consideration of recent anatomic and physiological findings regarding thalamic structure and functions. It is concluded that four related corticothalamic and/or thalamocortical mechanisms impact language processing: (1) selective engagement of task-relevant cortical areas in a heightened state of responsiveness in part through the nucleus reticularis (NR), (2) passing information from one cortical area to another through corticothalamo-cortical mechanisms, (3) sharpening the focus on task-relevant information through corticothalamo-cortical feedback mechanisms, and (4) selection of one language unit over another in the expression of a concept, accomplished in concert with basal ganglia loops. The relationship and interaction of these mechanisms is discussed and integrated with thalamic aphasia and neuroimaging data into a theory of thalamic functions in language. Published by Elsevier Inc.

  1. Frontotemporal dementia with severe thalamic involvement : a clinical and neuropathological study

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    Radanovic Márcia

    2003-01-01

    Full Text Available Frontotemporal dementia (FTD is the third-leading cause of cortical dementia after Alzheimer's disease and Lewy body dementia, and is characterized by a dementia where behavioral disturbances are prominent and appear early in the course of the disease. We report the case of a 58 year-old man affected by dementia with behavioral disturbances, in addition to rigid-hypokinetic and a lower motor neuron syndrome that were present at later stages of the illness. Neuroimaging studies showed frontotemporal atrophy. Neuropathological studies revealed intense thalamic neuronal loss and astrocytic gliosis, as well as moderate frontotemporal neuronal loss, astrocytosis and spongiform degeneration. Thalamic degeneration has previously been described among the wide group of neuropathological features of FTD. The aim of the present study is to show the clinical and neuropathological aspects of thalamic degeneration in FTD, along with its role in behavioral disturbances, a common finding in this condition.

  2. Neuroanatomical Relationships between Orexin/Hypocretin-Containing Neurons/Nerve Fibers and Nicotine-Induced c-Fos-Activated Cells of the Reward-Addiction Neurocircuitry

    Science.gov (United States)

    Dehkordi, Ozra; Rose, Jed E; Dávila-García, Martha I; Millis, Richard M; Mirzaei, Samar Ali; Manaye, Kebreten F; Jayam-Trouth, Annapurni

    2017-01-01

    Orexin/hypocretin-containing neurons in lateral hypothalamus (LH) are implicated in the neurobiology of nicotine addiction. However, the neuroanatomical relationships between orexin-neurons/nerve fibers and nicotine-activated cells within the reward-addiction neurocircuitry is not known. In the present study in mice, we first used c-Fos immunohistochemistry to identify CNS cells stimulated by an acute single injection of nicotine (NIC, 2 mg/kg, IP). Sequential double-labelling was then performed to identify the location of orexin-containing neurons and nerve fibers with respect to NIC-induced c-Fos activated cells and/or tyrosine hydroxylase (TH) immunoreactive (IR) cells of the mesocorticolimbic reward-addiction pathways. Orexin-IR nerve fibers and terminals were detected at multiple sites of the NIC reward-addiction circuitry in close apposition to, and intermingled with, NIC-induced c-Fos-IR cells of locus coeruleus (LC), ventral tegmental area (VTA), nucleus accumbens (Acb), LH and paraventricular thalamic nucleus (PVT). Double-labelling of orexin with TH showed frequent contact between orexin-IR nerve fibers and noradrenergic cells of LC. However, there was infrequent contact between the orexinergic fibers and the TH-expressing dopaminergic cells of VTA, dorsal raphe nucleus (DR), posterior hypothalamus (DA11), arcuate hypothalamic nucleus (DA12) and periventricular areas (DA14). The close anatomical contact between orexinergic nerve fibers and NIC-activated cells at multiple sites of the reward-addiction pathways suggests that orexinergic projections from LH are likely to be involved in modulating activity of the neurons that are directly impacted by acute administration of nicotine. PMID:29038792

  3. Altered thalamic functional connectivity in multiple sclerosis

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    Liu, Yaou; Liang, Peipeng; Duan, Yunyun; Huang, Jing; Ren, Zhuoqiong; Jia, Xiuqin [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Dong, Huiqing; Ye, Jing [Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Shi, Fu-Dong [Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052 (China); Butzkueven, Helmut [Department of Medicine, University of Melbourne, Parkville 3010 (Australia); Li, Kuncheng, E-mail: kunchengli55@gmail.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China)

    2015-04-15

    Highlights: •We demonstrated decreased connectivity between thalamus and cortical regions in MS. •Increased intra- and inter-thalamic connectivity was also observed in MS. •The increased functional connectivity is attenuated by increasing disease duration. -- Abstract: Objective: To compare thalamic functional connectivity (FC) in patients with multiple sclerosis (MS) and healthy controls (HC), and correlate these connectivity measures with other MRI and clinical variables. Methods: We employed resting-state functional MRI (fMRI) to examine changes in thalamic connectivity by comparing thirty-five patients with MS and 35 age- and sex-matched HC. Thalamic FC was investigated by correlating low frequency fMRI signal fluctuations in thalamic voxels with voxels in all other brain regions. Additionally thalamic volume fraction (TF), T2 lesion volume (T2LV), EDSS and disease duration were recorded and correlated with the FC changes. Results: MS patients were found to have a significantly lower TF than HC in bilateral thalami. Compared to HC, the MS group showed significantly decreased FC between thalamus and several brain regions including right middle frontal and parahippocampal gyri, and the left inferior parietal lobule. Increased intra- and inter-thalamic FC was observed in the MS group compared to HC. These FC alterations were not correlated with T2LV, thalamic volume or lesions. In the MS group, however, there was a negative correlation between disease duration and inter-thalamic connectivity (r = −0.59, p < 0.001). Conclusion: We demonstrated decreased FC between thalamus and several cortical regions, while increased intra- and inter-thalamic connectivity in MS patients. These complex functional changes reflect impairments and/or adaptations that are independent of T2LV, thalamic volume or presence of thalamic lesions. The negative correlation between disease duration and inter-thalamic connectivity could indicate an adaptive role of thalamus that is

  4. Communication skills and thalamic lesion: Strategies of rehabilitation.

    Science.gov (United States)

    Amaddii, Luisa; Centorrino, Santi; Cambi, Jacopo; Passali, Desiderio

    2014-01-01

    To describe the speech rehabilitation history of patients with thalamic lesions. Thalamic lesions can affect speech and language according to diverse thalamic nuclei involved. Because of the strategic functional position of the thalamus within the cognitive networks, its lesion can also interfere with other cognitive processes, such as attention, memory and executive functions. Alterations of these cognitive domains contribute significantly to language deficits, leading to communicative inefficacy. This fact must be considered in the rehabilitation efforts. Whereas evaluation of cognitive functions and communicative efficiency is different from that of aphasic disorder, treatment should also be different. The treatment must be focused on specific cognitive deficits with belief in the regaining of communicative ability, as well as it occurs in therapy of pragmatic disorder in traumatic brain injury: attention process training, mnemotechnics and prospective memory training. According to our experience: (a) there is a close correlation between cognitive processes and communication skills; (b) alterations of attention, memory and executive functions cause a loss of efficiency in the language use; and (c) appropriate cognitive treatment improves pragmatic competence and therefore the linguistic disorder. For planning a speech-therapy it is important to consider the relationship between cognitive functions and communication. The cognitive/behavioral treatment confirms its therapeutic efficiency for thalamic lesions. Copyright © 2014 Polish Otorhinolaryngology - Head and Neck Surgery Society. Published by Elsevier Urban & Partner Sp. z.o.o. All rights reserved.

  5. [Hypersomnia and thalamic and brain stem stroke: a study of seven patients].

    Science.gov (United States)

    Blanco, M; Espinosa, M; Arpa, J; Barreiro, P; Rodríguez-Albariño, A

    1999-01-01

    Thalamic and brainstem strokes are a cause of organic hypersomnia. In thalamic lesions it has been attributed to disruption of ascending activating impulses from the brainstem reticular formation and to insufficient spindling and slow-wave production, which depends upon activities of reticular thalamic nucleus and thalamocortical neurons, respectively. Reported sleep disorders in brainstem lesions have occasionally been contradictory and that is because of the presence of nearby structures in the brainstem with different functions in sleep-waking cycle. The aim of the study is to present the results of polysomnographic records in patients with thalamic and/or brainstem vascular lesions, and to correlate them with the anatomical structures affected. We have performed a polysomnographic study, (8-channel system), in patients with thalamic and/or brainstem strokes. All of them showed alterations of sleep-wake cycle. Neuroimaging studies were carried out in all patients. We report seven patients, 4 males and 3 females. Two cases presented thalamic strokes, in 3 the lesion was located in the brainstem and 2 patients had thalamo-mesencephalic lesions. All of them developed hypersomnia with an increase of NREM sleep. In patients with bilateral mesencephalic lesions we found that REM sleep was diminished as well. We have confirmed that lesions affecting thalamus and mesencephalic or pontine tegmental reticular formation are a cause of hypersomnia. The observation that this sleepiness is transient, supports the evidence of an extrathalamic alternative activating route.

  6. State-dependent architecture of thalamic reticular subnetworks.

    Science.gov (United States)

    Halassa, Michael M; Chen, Zhe; Wimmer, Ralf D; Brunetti, Philip M; Zhao, Shengli; Zikopoulos, Basilis; Wang, Fan; Brown, Emery N; Wilson, Matthew A

    2014-08-14

    Behavioral state is known to influence interactions between thalamus and cortex, which are important for sensation, action, and cognition. The thalamic reticular nucleus (TRN) is hypothesized to regulate thalamo-cortical interactions, but the underlying functional architecture of this process and its state dependence are unknown. By combining the first TRN ensemble recording with psychophysics and connectivity-based optogenetic tagging, we found reticular circuits to be composed of distinct subnetworks. While activity of limbic-projecting TRN neurons positively correlates with arousal, sensory-projecting neurons participate in spindles and show elevated synchrony by slow waves during sleep. Sensory-projecting neurons are suppressed by attentional states, demonstrating that their gating of thalamo-cortical interactions is matched to behavioral state. Bidirectional manipulation of attentional performance was achieved through subnetwork-specific optogenetic stimulation. Together, our findings provide evidence for differential inhibition of thalamic nuclei across brain states, where the TRN separately controls external sensory and internal limbic processing facilitating normal cognitive function. PAPERFLICK: Copyright © 2014 Elsevier Inc. All rights reserved.

  7. An ontological approach to describing neurons and their relationships

    Directory of Open Access Journals (Sweden)

    David J. Hamilton

    2012-04-01

    Full Text Available The advancement of neuroscience, perhaps the most information rich discipline of all the life sciences, requires basic frameworks for organizing the vast amounts of data generated by the research community to promote novel insights and integrated understanding. Since Cajal, the neuron remains a fundamental unit of the nervous system, yet even with the explosion of information technology, we still have few comprehensive or systematic strategies for aggregating cell-level knowledge. Progress toward this goal is hampered by the multiplicity of names for cells and by lack of a consensus on the criteria for defining neuron types. However, through umbrella projects like the Neuroscience Information Framework and the International Neuroinformatics Coordinating Facility, we have the opportunity to propose and implement an informatics infrastructure for establishing common tools and approaches to describe neurons through a standard terminology for nerve cells and a database (a Neuron Registry where these descriptions can be deposited and compared. This article provides an overview of the problem and outlines a solution approach utilizing ontological characterizations.

  8. Functional connectivity and dynamics of cortical-thalamic networks co-cultured in a dual compartment device

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    Kanagasabapathi, Thirukumaran T.; Massobrio, Paolo; Barone, Rocco Andrea; Tedesco, Mariateresa; Martinoia, Sergio; Wadman, Wytse J.; Decré, Michel M. J.

    2012-06-01

    Co-cultures containing dissociated cortical and thalamic cells may provide a unique model for understanding the pathophysiology in the respective neuronal sub-circuitry. In addition, developing an in vitro dissociated co-culture model offers the possibility of studying the system without influence from other neuronal sub-populations. Here we demonstrate a dual compartment system coupled to microelectrode arrays (MEAs) for co-culturing and recording spontaneous activities from neuronal sub-populations. Propagation of electrical activities between cortical and thalamic regions and their interdependence in connectivity is verified by means of a cross-correlation algorithm. We found that burst events originate in the cortical region and drive the entire cortical-thalamic network bursting behavior while mutually weak thalamic connections play a relevant role in sustaining longer burst events in cortical cells. To support these experimental findings, a neuronal network model was developed and used to investigate the interplay between network dynamics and connectivity in the cortical-thalamic system.

  9. The pairwise phase consistency in cortical network and its relationship with neuronal activation

    Directory of Open Access Journals (Sweden)

    Wang Daming

    2017-01-01

    Full Text Available Gamma-band neuronal oscillation and synchronization with the range of 30-90 Hz are ubiquitous phenomenon across numerous brain areas and various species, and correlated with plenty of cognitive functions. The phase of the oscillation, as one aspect of CTC (Communication through Coherence hypothesis, underlies various functions for feature coding, memory processing and behaviour performing. The PPC (Pairwise Phase Consistency, an improved coherence measure, statistically quantifies the strength of phase synchronization. In order to evaluate the PPC and its relationships with input stimulus, neuronal activation and firing rate, a simplified spiking neuronal network is constructed to simulate orientation columns in primary visual cortex. If the input orientation stimulus is preferred for a certain orientation column, neurons within this corresponding column will obtain higher firing rate and stronger neuronal activation, which consequently engender higher PPC values, with higher PPC corresponding to higher firing rate. In addition, we investigate the PPC in time resolved analysis with a sliding window.

  10. Reduced thalamic volume in preterm infants is associated with abnormal white matter metabolism independent of injury

    Energy Technology Data Exchange (ETDEWEB)

    Wisnowski, Jessica L. [Children' s Hospital Los Angeles, Department of Radiology, Los Angeles, CA (United States); University of Pittsburgh, Department of Pediatric Radiology, Children' s Hospital of Pittsburgh of UPMC, Pittsburgh, PA (United States); University of Southern California, Brain and Creativity Institute, Los Angeles, CA (United States); Ceschin, Rafael C. [University of Pittsburgh, Department of Pediatric Radiology, Children' s Hospital of Pittsburgh of UPMC, Pittsburgh, PA (United States); University of Pittsburgh, Department of Biomedical Informatics, Pittsburgh, PA (United States); Choi, So Young [University of Southern California, Brain and Creativity Institute, Los Angeles, CA (United States); Schmithorst, Vincent J. [University of Pittsburgh, Department of Pediatric Radiology, Children' s Hospital of Pittsburgh of UPMC, Pittsburgh, PA (United States); Painter, Michael J. [University of Pittsburgh, Department of Pediatrics, Division of Neurology, Childrens Hospital of Pittsburgh of UPMC, Pittsburgh, PA (United States); Nelson, Marvin D. [Children' s Hospital Los Angeles, Department of Radiology, Los Angeles, CA (United States); Blueml, Stefan [Children' s Hospital Los Angeles, Department of Radiology, Los Angeles, CA (United States); Rudi Schulte Research Institute, Santa Barbara, CA (United States); Panigrahy, Ashok [Children' s Hospital Los Angeles, Department of Radiology, Los Angeles, CA (United States); University of Pittsburgh, Department of Pediatric Radiology, Children' s Hospital of Pittsburgh of UPMC, Pittsburgh, PA (United States)

    2015-05-01

    Altered thalamocortical development is hypothesized to be a key substrate underlying neurodevelopmental disabilities in preterm infants. However, the pathogenesis of this abnormality is not well-understood. We combined magnetic resonance spectroscopy of the parietal white matter and morphometric analyses of the thalamus to investigate the association between white matter metabolism and thalamic volume and tested the hypothesis that thalamic volume would be associated with diminished N-acetyl-aspartate (NAA), a measure of neuronal/axonal maturation, independent of white matter injury. Data from 106 preterm infants (mean gestational age at birth: 31.0 weeks ± 4.3; range 23-36 weeks) who underwent MR examinations under clinical indications were included in this study. Linear regression analyses demonstrated a significant association between parietal white matter NAA concentration and thalamic volume. This effect was above and beyond the effect of white matter injury and age at MRI and remained significant even when preterm infants with punctate white matter lesions (pWMLs) were excluded from the analysis. Furthermore, choline, and among the preterm infants without pWMLs, lactate concentrations were also associated with thalamic volume. Of note, the associations between NAA and choline concentration and thalamic volume remained significant even when the sample was restricted to neonates who were term-equivalent age or older. These observations provide convergent evidence of a neuroimaging phenotype characterized by widespread abnormal thalamocortical development and suggest that the pathogenesis may involve impaired axonal maturation. (orig.)

  11. The neurobiology of thalamic amnesia: Contributions of medial thalamus and prefrontal cortex to delayed conditional discrimination.

    Science.gov (United States)

    Mair, Robert G; Miller, Rikki L A; Wormwood, Benjamin A; Francoeur, Miranda J; Onos, Kristen D; Gibson, Brett M

    2015-07-01

    Although medial thalamus is well established as a site of pathology associated with global amnesia, there is uncertainty about which structures are critical and how they affect memory function. Evidence from human and animal research suggests that damage to the mammillothalamic tract and the anterior, mediodorsal (MD), midline (M), and intralaminar (IL) nuclei contribute to different signs of thalamic amnesia. Here we focus on MD and the adjacent M and IL nuclei, structures identified in animal studies as critical nodes in prefrontal cortex (PFC)-related pathways that are necessary for delayed conditional discrimination. Recordings of PFC neurons in rats performing a dynamic delayed non-matching-to position (DNMTP) task revealed discrete populations encoding information related to planning, execution, and outcome of DNMTP-related actions and delay-related activity signaling previous reinforcement. Parallel studies recording the activity of MD and IL neurons and examining the effects of unilateral thalamic inactivation on the responses of PFC neurons demonstrated a close coupling of central thalamic and PFC neurons responding to diverse aspects of DNMTP and provide evidence that thalamus interacts with PFC neurons to give rise to complex goal-directed behavior exemplified by the DNMTP task. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Thalamic volume as a biomarker for disorders of consciousness

    Science.gov (United States)

    Rubeaux, Mathieu; Mahalingam, Jamuna Jayashri; Gomez, Francisco; Nelson, Marvin; Vanhaudenhuyse, Audrey; Bruno, Marie-Aurélie; Gosseries, Olivia; Laureys, Steven; Soddu, Andrea; Lepore, Natasha

    2015-01-01

    Disorders of consciousness (DOC) may be characterized by the degree at which consciousness is impaired, and include for example vegetative state (VS) and minimally conscious state (MCS) patients. Using a reliable marker as a measure of the level of consciousness in such patients is of utmost necessity and importance for their appropriate diagnosis and prognosis. Identification of VS and MCS states based on their behaviors sometimes leads to incorrect inferences due to the influence of a range of factors like motor impairment, fluctuating arousal levels and rapidly habituating responses to name a few.1 The extent of damage in the thalamus, a structure known for its role in arousal regulation, may provide an imaging biomarker to better differentiate between VS and MCS. In this study, we manually segmented the thalamus from T1-weighted brain MRI images in a large cohort of 19 VS and 23 MCS subjects that were examined using the French version of the Coma Recovery Scale Revised (CRS-R).2 This scale is the most trustworthy behavioural diagnosis tool3 for patients with DOC available. The aim was to determine whether a relationship between thalamus volume and consciousness level exists. Results show that total thalamic volume tends to decrease over time after a severe brain injury. Moreover, for subjects in chronic state, the thalamic volume seems to differ with respect to the degree of consciousness that was diagnosed. Finally, for these same chronic patients, the total thalamic volume is varying linearly as a function of the CRS-R score obtained, indicating that thalamic volume may be used as a biomarker to measure the level of consciousness.

  13. A stereological study of the mediodorsal thalamic nucleus in Down syndrome

    DEFF Research Database (Denmark)

    Karlsen, A S; Korbo, S; Uylings, H B M

    2014-01-01

    The total number of neurons and glial cells in the mediodorsal thalamic (MDT) nucleus of four aged females with Down syndrome (DS; mean age 69years) was estimated and compared to six age- and sex-matched controls. The MDT nucleus was delineated on coronal sections, and cell numbers (large and small...... neurons, oligodendrocytes, and astrocytes) were estimated using the optical fractionator technique. The DS brains had an average of 3.41×10(6) total neurons in the MDT nucleus in contrast to 5.97×10(6) in the controls, with no overlap (2p=0.004), affecting large (projecting) and small (local inhibitory...

  14. Bilateral paramedian thalamic syndrome after infection.

    Science.gov (United States)

    Kamaşak, Tülay; Sahin, Sevim; Eyüboğlu, İlker; Reis, Gökce Pinar; Cansu, Ali

    2015-02-01

    Although bilateral paramedian thalamic infarctions occur more frequently in adults than in children, they are rare entities at any age. The syndrome is thought to result from occlusion of the artery of Percheron, which arises as a common trunk from one of the posterior cerebral arteries to supply both paramedian thalamic regions. We describe two children with acute ischemic infarction involving both paramedian thalami developing after infection. The first patient developed mutism with ataxia after chicken pox infection. The second child developed headache, somnolence, agitation, and speech dysfunction following an upper respiratory tract infection. Bilateral thalamic lesions were documented on magnetic resonance imaging of both children. Bilateral infarctions of the paramedian thalamus may result in severe illness and impairment. Common clinical manifestations include disorientation, confusion, hypersomnolence, deep coma and "coma vigil," or akinetic mutism (awake unresponsiveness), as well as severe memory impairment. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Slow waves in mutually inhibitory neuronal networks

    Science.gov (United States)

    Jalics, Jozsi

    2004-05-01

    A variety of experimental and modeling studies have been performed to investigate wave propagation in networks of thalamic neurons and their relationship to spindle sleep rhythms. It is believed that spindle oscillations result from the reciprocal interaction between thalamocortical (TC) and thalamic reticular (RE) neurons. We consider a network of TC and RE cells reduced to a one-layer network model and represented by a system of singularly perturbed integral-differential equations. Geometric singular perturbation methods are used to prove the existence of a locally unique slow wave pulse that propagates along the network. By seeking a slow pulse solution, we reformulate the problem to finding a heteroclinic orbit in a 3D system of ODEs with two additional constraints on the location of the orbit at two distinct points in time. In proving the persistence of the singular heteroclinic orbit, difficulties arising from the solution passing near points where normal hyperbolicity is lost on a 2D critical manifold are overcome by employing results by Wechselberger [Singularly perturbed folds and canards in R3, Thesis, TU-Wien, 1998].

  16. Language disturbances from mesencephalo-thalamic infarcts. Identification of thalamic nuclei by CT-reconstructions

    Energy Technology Data Exchange (ETDEWEB)

    Lazzarino, L.G.; Nicolai, A.; Valassi, F. (Ospedale Civile di Gorizia (Italy). Div. di Neurologia); Biasizzo, E. (Ospedale di Udine (Italy). Servizio di Neuroradiologia)

    1991-08-01

    The authors report the cases of two patients with CT-documented paramedian mesencephalo-thalamic infarcts, showing language disturbances. The first patient showed a non fluent, transcortical motor-like aphasia, the other had a fluent but severely paraphasic language disorder. The CT study disclosed that it was the dorso-median thalamic nucleus that was mostly involved in both cases. These findings agree with a few previous pathological studies suggesting that the paramedian thalamic nuclei, particlularly the dorso-median nucleus may play some role in language disturbances. However the anatomical basis for thalamic aphasia remains speculative, taking into account the importantce of cortical connections in the origin of subcortical neuropsychological disturbances. (orig.).

  17. An Ultrastructural Study of the Thalamic Input to Layer 4 of Primary Motor and Primary Somatosensory Cortex in the Mouse.

    Science.gov (United States)

    Bopp, Rita; Holler-Rickauer, Simone; Martin, Kevan A C; Schuhknecht, Gregor F P

    2017-03-01

    The traditional classification of primary motor cortex (M1) as an agranular area has been challenged recently when a functional layer 4 (L4) was reported in M1. L4 is the principal target for thalamic input in sensory areas, which raises the question of how thalamocortical synapses formed in M1 in the mouse compare with those in neighboring sensory cortex (S1). We identified thalamic boutons by their immunoreactivity for the vesicular glutamate transporter 2 (VGluT2) and performed unbiased disector counts from electron micrographs. We discovered that the thalamus contributed proportionately only half as many synapses to the local circuitry of L4 in M1 compared with S1. Furthermore, thalamic boutons in M1 targeted spiny dendrites exclusively, whereas ∼9% of synapses were formed with dendrites of smooth neurons in S1. VGluT2 + boutons in M1 were smaller and formed fewer synapses per bouton on average (1.3 vs 2.1) than those in S1, but VGluT2 + synapses in M1 were larger than in S1 (median postsynaptic density areas of 0.064 μm 2 vs 0.042 μm 2 ). In M1 and S1, thalamic synapses formed only a small fraction (12.1% and 17.2%, respectively) of all of the asymmetric synapses in L4. The functional role of the thalamic input to L4 in M1 has largely been neglected, but our data suggest that, as in S1, the thalamic input is amplified by the recurrent excitatory connections of the L4 circuits. The lack of direct thalamic input to inhibitory neurons in M1 may indicate temporal differences in the inhibitory gating in L4 of M1 versus S1. SIGNIFICANCE STATEMENT Classical interpretations of the function of primary motor cortex (M1) emphasize its lack of the granular layer 4 (L4) typical of sensory cortices. However, we show here that, like sensory cortex (S1), mouse M1 also has the canonical circuit motif of a core thalamic input to the middle cortical layer and that thalamocortical synapses form a small fraction (M1: 12%; S1: 17%) of all asymmetric synapses in L4 of both areas

  18. Thalamic morphology in schizophrenia and schizoaffective disorder.

    Science.gov (United States)

    Smith, Matthew J; Wang, Lei; Cronenwett, Will; Mamah, Daniel; Barch, Deanna M; Csernansky, John G

    2011-03-01

    Biomarkers are needed that can distinguish between schizophrenia and schizoaffective disorder to inform the ongoing debate over the diagnostic boundary between these two disorders. Neuromorphometric abnormalities of the thalamus have been reported in individuals with schizophrenia and linked to core features of the disorder, but have not been similarly investigated in individuals with schizoaffective disorder. In this study, we examine whether individuals with schizoaffective disorder have a pattern of thalamic deformation that is similar or different to the pattern found in individuals with schizophrenia. T1-weighted magnetic resonance images were collected from individuals with schizophrenia (n = 47), individuals with schizoaffective disorder (n = 15), and controls (n = 42). Large-deformation, high-dimensional brain mapping was used to obtain three-dimensional surfaces of the thalamus. Multiple analyses of variance were used to test for group differences in volume and measures of surface shape. Individuals with schizophrenia or schizoaffective disorder have similar thalamic volumes. Thalamic surface shape deformation associated with schizophrenia suggests selective involvement of the anterior and posterior thalamus, while deformations in mediodorsal and ventrolateral regions were observed in both groups. Schizoaffective disorder had distinct deformations in medial and lateral thalamic regions. Abnormalities distinct to schizoaffective disorder suggest involvement of the central and ventroposterior medial thalamus which may be involved in mood circuitry, dorsolateral nucleus which is involved in recall processing, and the lateral geniculate nucleus which is involved in visual processing. Copyright © 2010 Elsevier Ltd. All rights reserved.

  19. Cortically-controlled population stochastic facilitation as a plausible substrate for guiding sensory transfer across the thalamic gateway.

    Directory of Open Access Journals (Sweden)

    Sébastien Béhuret

    Full Text Available The thalamus is the primary gateway that relays sensory information to the cerebral cortex. While a single recipient cortical cell receives the convergence of many principal relay cells of the thalamus, each thalamic cell in turn integrates a dense and distributed synaptic feedback from the cortex. During sensory processing, the influence of this functional loop remains largely ignored. Using dynamic-clamp techniques in thalamic slices in vitro, we combined theoretical and experimental approaches to implement a realistic hybrid retino-thalamo-cortical pathway mixing biological cells and simulated circuits. The synaptic bombardment of cortical origin was mimicked through the injection of a stochastic mixture of excitatory and inhibitory conductances, resulting in a gradable correlation level of afferent activity shared by thalamic cells. The study of the impact of the simulated cortical input on the global retinocortical signal transfer efficiency revealed a novel control mechanism resulting from the collective resonance of all thalamic relay neurons. We show here that the transfer efficiency of sensory input transmission depends on three key features: i the number of thalamocortical cells involved in the many-to-one convergence from thalamus to cortex, ii the statistics of the corticothalamic synaptic bombardment and iii the level of correlation imposed between converging thalamic relay cells. In particular, our results demonstrate counterintuitively that the retinocortical signal transfer efficiency increases when the level of correlation across thalamic cells decreases. This suggests that the transfer efficiency of relay cells could be selectively amplified when they become simultaneously desynchronized by the cortical feedback. When applied to the intact brain, this network regulation mechanism could direct an attentional focus to specific thalamic subassemblies and select the appropriate input lines to the cortex according to the descending

  20. Thalamic reticular input to the rat visual thalamus: a single fiber study using biocytin as an anterograde tracer.

    Science.gov (United States)

    Pinault, D; Bourassa, J; Deschênes, M

    1995-01-23

    This study describes the axonal projections of single thalamic reticular (TR) neurons within the visual thalamus in rats. Experiments were performed under urethane anesthesia and reticular cells were labeled by extracellular or juxtacellular microiontophoretic applications of biocytin. The axonal arborizations of 19 TR cells projecting to the dorsal lateral geniculate nucleus (DLG) or to the lateral dorsal/lateral posterior complex (LD/LP) were reconstructed from serial horizontal sections. It was found that single TR cells projected within the limits of a single thalamic nucleus, either the DLG or the LD/LP complex, where their terminal fields formed rostrocaudally oriented rods (length: approximately 800 microns; diameter: approximately 100 microns) densely packed with grape-like boutons and varicosities. In addition, none of the labeled TR cells possessed recurrent axonal collaterals that ramified within the reticular complex itself. The functional implications of these morphological data for the synchronization of thalamic oscillations are discussed.

  1. The special relationship: glia-neuron interactions in the neuroendocrine hypothalamus.

    Science.gov (United States)

    Clasadonte, Jerome; Prevot, Vincent

    2018-01-01

    Natural fluctuations in physiological conditions require adaptive responses involving rapid and reversible structural and functional changes in the hypothalamic neuroendocrine circuits that control homeostasis. Here, we discuss the data that implicate hypothalamic glia in the control of hypothalamic neuroendocrine circuits, specifically neuron-glia interactions in the regulation of neurosecretion as well as neuronal excitability. Mechanistically, the morphological plasticity displayed by distal processes of astrocytes, pituicytes and tanycytes modifies the geometry and diffusion properties of the extracellular space. These changes alter the relationship between glial cells of the hypothalamus and adjacent neuronal elements, especially at specialized intersections such as synapses and neurohaemal junctions. The structural alterations in turn lead to functional plasticity that alters the release and spread of neurotransmitters, neuromodulators and gliotransmitters, as well as the activity of discrete glial signalling pathways that mediate feedback by peripheral signals to the hypothalamus. An understanding of the contributions of these and other non-neuronal cell types to hypothalamic neuroendocrine function is thus critical both to understand physiological processes such as puberty, the maintenance of bodily homeostasis and ageing and to develop novel therapeutic strategies for dysfunctions of these processes, such as infertility and metabolic disorders.

  2. Structure-Dynamics Relationships in Bursting Neuronal Networks Revealed Using a Prediction Framework

    Science.gov (United States)

    Mäki-Marttunen, Tuomo; Aćimović, Jugoslava; Ruohonen, Keijo; Linne, Marja-Leena

    2013-01-01

    The question of how the structure of a neuronal network affects its functionality has gained a lot of attention in neuroscience. However, the vast majority of the studies on structure-dynamics relationships consider few types of network structures and assess limited numbers of structural measures. In this in silico study, we employ a wide diversity of network topologies and search among many possibilities the aspects of structure that have the greatest effect on the network excitability. The network activity is simulated using two point-neuron models, where the neurons are activated by noisy fluctuation of the membrane potential and their connections are described by chemical synapse models, and statistics on the number and quality of the emergent network bursts are collected for each network type. We apply a prediction framework to the obtained data in order to find out the most relevant aspects of network structure. In this framework, predictors that use different sets of graph-theoretic measures are trained to estimate the activity properties, such as burst count or burst length, of the networks. The performances of these predictors are compared with each other. We show that the best performance in prediction of activity properties for networks with sharp in-degree distribution is obtained when the prediction is based on clustering coefficient. By contrast, for networks with broad in-degree distribution, the maximum eigenvalue of the connectivity graph gives the most accurate prediction. The results shown for small () networks hold with few exceptions when different neuron models, different choices of neuron population and different average degrees are applied. We confirm our conclusions using larger () networks as well. Our findings reveal the relevance of different aspects of network structure from the viewpoint of network excitability, and our integrative method could serve as a general framework for structure-dynamics studies in biosciences. PMID:23935998

  3. Urethane anesthesia depresses activities of thalamocortical neurons and alters its response to nociception in terms of dual firing modes

    Directory of Open Access Journals (Sweden)

    Yeowool eHuh

    2013-10-01

    Full Text Available Anesthetics are often used to characterize the activity of single neurons in-vivo for its advantages such as reduced noise level and convenience in noxious stimulations. Of the anesthetics, urethane had been widely used in some thalamic studies under the assumption that sensory signals are still relayed to the thalamus under urethane anesthesia and that thalamic response would therefore reflect the response of the awake state. We tested whether this assumption stands by comparing thalamic activity in terms of tonic and burst firing modes during ‘the awake state’ or under ‘urethane anesthesia’ utilizing the extracellular single unit recording technique. First we have tested how thalamic relay neurons respond to the introduction of urethane and then tested how urethane influences thalamic discharges under formalin-induced nociception. Urethane significantly depressed overall firing rates of thalamic relay neurons, which was sustained despite the delayed increase of burst activity over the 4 hour recording period. Thalamic response to nociception under anesthesia was also similar overall except for the slight and transient increase of burst activity. Overall, results demonstrated that urethane suppresses the activity of thalamic relay neurons and that, despite the slight fluctuation of burst firing, formalin-induced nociception cannot significantly change the firing pattern of thalamic relay neurons that was caused by urethane.

  4. Mathematical Relationships between Neuron Morphology and Neurite Growth Dynamics in Drosophila melanogaster Larva Class IV Sensory Neurons

    Science.gov (United States)

    Ganguly, Sujoy; Liang, Xin; Grace, Michael; Lee, Daniel; Howard, Jonathon

    The morphology of neurons is diverse and reflects the diversity of neuronal functions, yet the principles that govern neuronal morphogenesis are unclear. In an effort to better understand neuronal morphogenesis we will be focusing on the development of the dendrites of class IV sensory neuron in Drosophila melanogaster. In particular we attempt to determine how the the total length, and the number of branches of dendrites are mathematically related to the dynamics of neurite growth and branching. By imaging class IV neurons during early embryogenesis we are able to measure the change in neurite length l (t) as a function of time v (t) = dl / dt . We found that the distribution of v (t) is well characterized by a hyperbolic secant distribution, and that the addition of new branches per unit time is well described by a Poisson process. Combining these measurements with the assumption that branching occurs with equal probability anywhere along the dendrite we were able to construct a mathematical model that provides reasonable agreement with the observed number of branches, and total length of the dendrites of the class IV sensory neuron.

  5. Simultaneous Top-down Modulation of the Primary Somatosensory Cortex and Thalamic Nuclei during Active Tactile Discrimination

    Science.gov (United States)

    Pais-Vieira, Miguel; Lebedev, Mikhail A.; Wiest, Michael C.; Nicolelis, Miguel A.L.

    2013-01-01

    The rat somatosensory system contains multiple thalamocortical loops (TCL) that altogether process, in fundamentally different ways, tactile stimuli delivered passively or actively sampled. To elucidate potential top-down mechanisms that govern TCL processing in awake, behaving animals, we simultaneously recorded neuronal ensemble activity across multiple cortical and thalamic areas while rats performed an active aperture discrimination task. Single neurons located in the primary somatosensory cortex (S1), the ventroposterior medial (VPM) and the posterior medial (POM) thalamic nuclei of the trigeminal somatosensory pathways exhibited prominent anticipatory firing modulations prior to the whiskers touching the aperture edges. This cortical and thalamic anticipatory firing could not be explained by whisker movements or whisker stimulation, because neither trigeminal ganglion sensory-evoked responses nor EMG activity were detected during the same period. Both thalamic and S1 anticipatory activity were predictive of the animal’s discrimination accuracy. Inactivation of the primary motor cortex (M1) with muscimol affected anticipatory patterns in S1 and the thalamus, and impaired the ability to predict the animal’s performance accuracy based on thalamocortical anticipatory activity. These findings suggest that neural processing in TCLs is launched in anticipation of whisker contact with objects, depends on top-down effects generated in part by M1 activity, and cannot be explained by the classical feedforward model of the rat trigeminal system. PMID:23447616

  6. Electrophysiology and Pharmacology of the Corticothalamic Input to Lateral Thalamic Nuclei: an Intracellular Study in the Cat.

    Science.gov (United States)

    Deschêenes, Martin; Hu, Bin

    1990-02-01

    Though most experimental evidence indicates that the corticothalamic (CT) pathway would exert a direct excitatory action on thalamic relay neurons, the electrophysiological features of this excitation have never been clearly described. A methodological problem in previous electrophysiological studies was that direct corticofugal effects on relay cells could not be separated from those mediated by collateral activation of reticular thalamic neurons. In the present study, the reticular complex was lesioned by kainic acid and the CT response of relay neurons of the ventral lateral nucleus was recorded intracellularly in cats under pentobarbital or urethane anaesthesia. Following reticular thalamic lesions, a prominent depolarization was triggered in thalamic relay cells by stimulation of the CT pathway. This depolarization strongly drove spike discharges, and its amplitude augmented when the stimulation rate exceeded 2 Hz. Tetanizing the CT input with short trains (100 - 200 Hz for 200 - 300 ms) produced a similar augmentation to test volleys for 15 - 30 s after the tetanos. The CT excitation and its frequency-dependent augmentation were depressed by ketamine injection or by local application of N-methyl-D-aspartate (NMDA) antagonists. The augmenting phenomenon appeared strictly homosynaptic. For instance, it did not appear during repetitive stimulation of the cerebellar input, nor did the CT input potentiate subthreshold synaptic potentials of cerebellar origin during a conditioning procedure. Conversely, the cerebellar excitation was depressed when it occurred during the CT depolarization. It is concluded that the direct synaptic responses induced by CT fibres in relay neurons are mediated at least partly by the activation of NMDA receptors. Moreover, the marked non-linear additivity of cerebellar and CT synaptic potentials raises questions concerning the presumed improvement of thalamic transmission of peripheral informations ensured by the CT input. Instead, both

  7. Morphological Abnormalities of Thalamic Subnuclei in Migraine

    DEFF Research Database (Denmark)

    Magon, Stefano; May, Arne; Stankewitz, Anne

    2015-01-01

    . SIGNIFICANCE STATEMENT: This multicenter imaging study shows morphological thalamic abnormalities in a large cohort of patients with episodic migraine compared with healthy subjects using state-of-the-art MRI and advanced, fully automated multiatlas segmentation techniques. The results stress that migraine...... is a disorder of the CNS in which not only is brain function abnormal, but also brain structure is undergoing significant remodeling....... techniques in substantial patient populations are lacking. In the present study, we investigated changes of thalamic volume and shape in a large multicenter cohort of patients with migraine. High-resolution T1-weighted MRI data acquired at 3 tesla in 131 patients with migraine (38 with aura; 30.8 ± 9 years...

  8. Two Case Report With Bilateral Thalamic Infarct

    Directory of Open Access Journals (Sweden)

    Utku Cenikli

    2017-04-01

    Full Text Available Bilateral thalamic infarction is a rare clinical condition. Thalamo-perforan arteries are arise from the same vascular territory in nearly one third of the cases and oclussion of it causes bilateral infacts. Clinical presentation can be altered mental status, decrease alertness, memory problems, mood disorders, cognitive problems and vertical gaze palsy. In this report we present two cases with different clinical status.

  9. Short-term synaptic plasticity in the nociceptive thalamic-anterior cingulate pathway.

    Science.gov (United States)

    Shyu, Bai-Chuang; Vogt, Brent A

    2009-09-04

    Although the mechanisms of short- and long-term potentiation of nociceptive-evoked responses are well known in the spinal cord, including central sensitization, there has been a growing body of information on such events in the cerebral cortex. In view of the importance of anterior cingulate cortex (ACC) in chronic pain conditions, this review considers neuronal plasticities in the thalamocingulate pathway that may be the earliest changes associated with such syndromes. A single nociceptive electrical stimulus to the sciatic nerve induced a prominent sink current in the layer II/III of the ACC in vivo, while high frequency stimulation potentiated the response of this current. Paired-pulse facilitation by electrical stimulation of midline, mediodorsal and intralaminar thalamic nuclei (MITN) suggesting that the MITN projection to ACC mediates the nociceptive short-term plasticity. The short-term synaptic plasticities were evaluated for different inputs in vitro where the medial thalamic and contralateral corpus callosum afferents were compared. Stimulation of the mediodorsal afferent evoked a stronger short-term synaptic plasticity and effectively transferred the bursting thalamic activity to cingulate cortex that was not true for contralateral stimulation. This short-term enhancement of synaptic transmission was mediated by polysynaptic pathways and NMDA receptors. Layer II/III neurons of the ACC express a short-term plasticity that involves glutamate and presynaptic calcium influx and is an important mechanism of the short-term plasticity. The potentiation of ACC neuronal activity induced by thalamic bursting suggest that short-term synaptic plasticities enable the processing of nociceptive information from the medial thalamus and this temporal response variability is particularly important in pain because temporal maintenance of the response supports cortical integration and memory formation related to noxious events. Moreover, these modifications of cingulate

  10. Dynamics of Action Potential Initiation in the GABAergic Thalamic Reticular Nucleus In Vivo

    Science.gov (United States)

    Muñoz, Fabián; Fuentealba, Pablo

    2012-01-01

    Understanding the neural mechanisms of action potential generation is critical to establish the way neural circuits generate and coordinate activity. Accordingly, we investigated the dynamics of action potential initiation in the GABAergic thalamic reticular nucleus (TRN) using in vivo intracellular recordings in cats in order to preserve anatomically-intact axo-dendritic distributions and naturally-occurring spatiotemporal patterns of synaptic activity in this structure that regulates the thalamic relay to neocortex. We found a wide operational range of voltage thresholds for action potentials, mostly due to intrinsic voltage-gated conductances and not synaptic activity driven by network oscillations. Varying levels of synchronous synaptic inputs produced fast rates of membrane potential depolarization preceding the action potential onset that were associated with lower thresholds and increased excitability, consistent with TRN neurons performing as coincidence detectors. On the other hand the presence of action potentials preceding any given spike was associated with more depolarized thresholds. The phase-plane trajectory of the action potential showed somato-dendritic propagation, but no obvious axon initial segment component, prominent in other neuronal classes and allegedly responsible for the high onset speed. Overall, our results suggest that TRN neurons could flexibly integrate synaptic inputs to discharge action potentials over wide voltage ranges, and perform as coincidence detectors and temporal integrators, supported by a dynamic action potential threshold. PMID:22279567

  11. Impaired visual short-term memory capacity is distinctively associated with structural connectivity of the posterior thalamic radiation and the splenium of the corpus callosum in preterm-born adults.

    Science.gov (United States)

    Menegaux, Aurore; Meng, Chun; Neitzel, Julia; Bäuml, Josef G; Müller, Hermann J; Bartmann, Peter; Wolke, Dieter; Wohlschläger, Afra M; Finke, Kathrin; Sorg, Christian

    2017-04-15

    Preterm birth is associated with an increased risk for lasting changes in both the cortico-thalamic system and attention; however, the link between cortico-thalamic and attention changes is as yet little understood. In preterm newborns, cortico-cortical and cortico-thalamic structural connectivity are distinctively altered, with increased local clustering for cortico-cortical and decreased integrity for cortico-thalamic connectivity. In preterm-born adults, among the various attention functions, visual short-term memory (vSTM) capacity is selectively impaired. We hypothesized distinct associations between vSTM capacity and the structural integrity of cortico-thalamic and cortico-cortical connections, respectively, in preterm-born adults. A whole-report paradigm of briefly presented letter arrays based on the computationally formalized Theory of Visual Attention (TVA) was used to quantify parameter vSTM capacity in 26 preterm- and 21 full-term-born adults. Fractional anisotropy (FA) of posterior thalamic radiations and the splenium of the corpus callosum obtained by diffusion tensor imaging were analyzed by tract-based spatial statistics and used as proxies for cortico-thalamic and cortico-cortical structural connectivity. The relationship between vSTM capacity and cortico-thalamic and cortico-cortical connectivity, respectively, was significantly modified by prematurity. In full-term-born adults, the higher FA in the right posterior thalamic radiation the higher vSTM capacity; in preterm-born adults this FA-vSTM-relationship was inversed. In the splenium, higher FA was correlated with higher vSTM capacity in preterm-born adults, whereas no significant relationship was evident in full-term-born adults. These results indicate distinct associations between cortico-thalamic and cortico-cortical integrity and vSTM capacity in preterm-and full-term-born adults. Data suggest compensatory cortico-cortical fiber re-organization for attention deficits after preterm delivery

  12. MM2-thalamic Creutzfeldt-Jakob disease: neuropathological, biochemical and transmission studies identify a distinctive prion strain.

    Science.gov (United States)

    Moda, Fabio; Suardi, Silvia; Di Fede, Giuseppe; Indaco, Antonio; Limido, Lucia; Vimercati, Chiara; Ruggerone, Margherita; Campagnani, Ilaria; Langeveld, Jan; Terruzzi, Alessandro; Brambilla, Antonio; Zerbi, Pietro; Fociani, Paolo; Bishop, Matthew T; Will, Robert G; Manson, Jean C; Giaccone, Giorgio; Tagliavini, Fabrizio

    2012-09-01

    In Creutzfeldt-Jakob disease (CJD), molecular typing based on the size of the protease resistant core of the disease-associated prion protein (PrP(Sc) ) and the M/V polymorphism at codon 129 of the PRNP gene correlates with the clinico-pathologic subtypes. Approximately 95% of the sporadic 129MM CJD patients are characterized by cerebral deposition of type 1 PrP(Sc) and correspond to the classic clinical CJD phenotype. The rare 129MM CJD patients with type 2 PrP(Sc) are further subdivided in a cortical and a thalamic form also indicated as sporadic fatal insomnia. We observed two young patients with MM2-thalamic CJD. Main neuropathological features were diffuse, synaptic PrP immunoreactivity in the cerebral cortex and severe neuronal loss and gliosis in the thalamus and olivary nucleus. Western blot analysis showed the presence of type 2A PrP(Sc) . Challenge of transgenic mice expressing 129MM human PrP showed that MM2-thalamic sporadic CJD (sCJD) was able to transmit the disease, at variance with MM2-cortical sCJD. The affected mice showed deposition of type 2A PrP(Sc) , a scenario that is unprecedented in this mouse line. These data indicate that MM2-thalamic sCJD is caused by a prion strain distinct from the other sCJD subtypes including the MM2-cortical form. © 2012 The Authors; Brain Pathology © 2012 International Society of Neuropathology.

  13. Relationships between neuronal cell adhesion molecule and LHRH neurons in the urodele brain: a developmental immunohistochemical study

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    S Gianola

    2009-12-01

    Full Text Available Polysialic acid (PSA, a homopolymer attached to neural cell adhesion molecule (NCAM is considered a major hallmark of vertebrate cell migration. We studied the distribution of PSA-NCAM by immunohistochemistry, during brain development, in two urodele amphibians, Pleurodeles waltl and the neotenic newt Ambystoma mexicanum. In both species a gradual increase of immunolabelling was observed throughout the brain from developmental stage 30 to stage 52. At the onset of metamorphosis, some differences became evident: in Pleurodeles immunostaining was gradually restricted to the olfactory system while in Ambystoma, PSA-NCAM maintained a more extended distribution (for example throughout the telencephalic walls suggesting, for the brain of this latter species, a rather preserved neuronal plasticity. The aim of the present work was to correlate the above described PSA-NCAMimmunoreactivity (IR with the distribution of luteinizing hormone-releasing hormone (LH-RH containing neurons, which represent a well known example of neural elements migrating from the olfactory placode. LHRH-IR, undetectable till stage 30, was later found together with PSA-NCAM-IR in both the olfactory system and septo-hypothalamic areas. Such observations further support a role of PSA in providing a migration route toward the establishment of a part, at least, of the urodele LHRH system. The possible functional meaning of the LHRH-containing neurons localized between dorsal and ventral thalamus of Ambystoma, never reported before in this area, almost devoid of PSANCAM- IR, is discussed.

  14. The relationship between MR images and clinical findings in neuronal migration disorders

    Energy Technology Data Exchange (ETDEWEB)

    Onuma, Akira; Kobayashi, Yasuko [Takuto Rehabilitation Center for Disabled Children, Sendai (Japan); Iinuma, Kazuie

    1997-07-01

    Among the variable manifestating conditions of neuronal migration disorders, mental retardation, motor disturbance and epilepsy are the main features of developmental disabilities. We analyzed the relationship between clinical symptoms and magnetic resonance (MR) images, including surface anatomy scan (SAS). Thirty-nine patients (23 males, 16 females; mean age 6.1 years) with neuronal migration disorders were studied. The diagnoses were cerebral palsy in 23 cases, mental retardation in 4, West syndrome in 4, Fukuyama type congenital muscular dystrophy (FCMD) in 6, Walker-Warburg syndrome in 1 and Dubowitz syndrome in 1. Cortical dysplasias were classified into the following 7 groups, mainly based on the SAS findings: complete agyria (AG 1), mixture of agyria and pachygyria (AG 2), bilateral complete pachygyria (BP 1), diffuse pachygyria with marked widening of the bilateral superior frontal gyrus (BP 2), unilateral pachygyria with hemispheric atrophy or hemimegalencephaly (UP), focal cortical dysplasia (FP) and other findings such as solitary schizencephaly (Others). Most cases of AG 1 and AG 2 showed spastic quadriplegia (6/7) and symptomatic generalized epilepsy (5/7), whereas cases of BP 1 showed spasticity only in 1/8 and epilepsy in 7/8. Hemiplegia was observed in 6/7 of UP, 2/8 of FP and 2/4 of Others. Partial epilepsy was observed in 2/7 of UP and 1/8 of FP. Intellectual level was variable in BP 1, UP, FP and Others, but all cases showed severe mental retardation in AG 1, AG 2 and BP 2. BP 2 was observed in all cases of typical FCMD (5/5). The birth weight was less than 2,500 g in 6/7 of UP. The structural findings well correlated with clinical symptoms and epileptic seizure types. The surface anatomy scan was a very useful technique for detecting cortical dysplasias. (author)

  15. Thalamic input to distal apical dendrites in neocortical layer 1 is massive and highly convergent.

    Science.gov (United States)

    Rubio-Garrido, Pablo; Pérez-de-Manzo, Flor; Porrero, César; Galazo, Maria J; Clascá, Francisco

    2009-10-01

    Input to apical dendritic tufts is now deemed crucial for associative learning, attention, and similar "feedback" interactions in the cerebral cortex. Excitatory input to apical tufts in neocortical layer 1 has been traditionally assumed to be predominantly cortical, as thalamic pathways directed to this layer were regarded relatively scant and diffuse. However, the sensitive tracing methods used in the present study show that, throughout the rat neocortex, large numbers (mean approximately 4500/mm(2)) of thalamocortical neurons converge in layer 1 and that this convergence gives rise to a very high local density of thalamic terminals. Moreover, we show that the layer 1-projecting neurons are present in large numbers in most, but not all, motor, association, limbic, and sensory nuclei of the rodent thalamus. Some layer 1-projecting axons branch to innervate large swaths of the cerebral hemisphere, whereas others arborize within only a single cortical area. Present data imply that realistic modeling of cortical circuitry should factor in a dense axonal canopy carrying highly convergent thalamocortical input to pyramidal cell apical tufts. In addition, they are consistent with the notion that layer 1-projecting axons may be a robust anatomical substrate for extensive "feedback" interactions between cortical areas via the thalamus.

  16. Thalamic Cav3.1 T-type Ca2+ channel plays a crucial role in stabilizing sleep

    Science.gov (United States)

    Anderson, Matthew P.; Mochizuki, Takatoshi; Xie, Jinghui; Fischler, Walter; Manger, Jules P.; Talley, Edmund M.; Scammell, Thomas E.; Tonegawa, Susumu

    2005-01-01

    It has long been suspected that sensory signal transmission is inhibited in the mammalian brain during sleep. We hypothesized that Cav3.1 T-type Ca2+ channel currents inhibit thalamic sensory transmission to promote sleep. We found that T-type Ca2+ channel activation caused prolonged inhibition (>9 s) of action-potential firing in thalamic projection neurons of WT but not Cav3.1 knockout mice. Inhibition occurred with synaptic transmission blocked and required an increase of intracellular Ca2+. Furthermore, focal deletion of the gene encoding Cav3.1 from the rostral–midline thalamus by using Cre/loxP recombination led to frequent and prolonged arousal, which fragmented and reduced sleep. Interestingly, sleep was not disturbed when Cav3.1 was deleted from cortical pyramidal neurons. These findings support the hypothesis that thalamic T-type Ca2+ channels are required to block transmission of arousal signals through the thalamus and to stabilize sleep. PMID:15677322

  17. Synchronization of Isolated Downstates (K-Complexes) May Be Caused by Cortically-Induced Disruption of Thalamic Spindling

    Science.gov (United States)

    Mak-McCully, Rachel A.; Deiss, Stephen R.; Rosen, Burke Q.; Jung, Ki-Young; Sejnowski, Terrence J.; Bastuji, Hélène; Rey, Marc

    2014-01-01

    Sleep spindles and K-complexes (KCs) define stage 2 NREM sleep (N2) in humans. We recently showed that KCs are isolated downstates characterized by widespread cortical silence. We demonstrate here that KCs can be quasi-synchronous across scalp EEG and across much of the cortex using electrocorticography (ECOG) and localized transcortical recordings (bipolar SEEG). We examine the mechanism of synchronous KC production by creating the first conductance based thalamocortical network model of N2 sleep to generate both spontaneous spindles and KCs. Spontaneous KCs are only observed when the model includes diffuse projections from restricted prefrontal areas to the thalamic reticular nucleus (RE), consistent with recent anatomical findings in rhesus monkeys. Modeled KCs begin with a spontaneous focal depolarization of the prefrontal neurons, followed by depolarization of the RE. Surprisingly, the RE depolarization leads to decreased firing due to disrupted spindling, which in turn is due to depolarization-induced inactivation of the low-threshold Ca2+ current (IT). Further, although the RE inhibits thalamocortical (TC) neurons, decreased RE firing causes decreased TC cell firing, again because of disrupted spindling. The resulting abrupt removal of excitatory input to cortical pyramidal neurons then leads to the downstate. Empirically, KCs may also be evoked by sensory stimuli while maintaining sleep. We reproduce this phenomenon in the model by depolarization of either the RE or the widely-projecting prefrontal neurons. Again, disruption of thalamic spindling plays a key role. Higher levels of RE stimulation also cause downstates, but by directly inhibiting the TC neurons. SEEG recordings from the thalamus and cortex in a single patient demonstrated the model prediction that thalamic spindling significantly decreases before KC onset. In conclusion, we show empirically that KCs can be widespread quasi-synchronous cortical downstates, and demonstrate with the first model

  18. Increased thalamic resting-state connectivity as a core driver of LSD-induced hallucinations.

    Science.gov (United States)

    Müller, F; Lenz, C; Dolder, P; Lang, U; Schmidt, A; Liechti, M; Borgwardt, S

    2017-12-01

    It has been proposed that the thalamocortical system is an important site of action of hallucinogenic drugs and an essential component of the neural correlates of consciousness. Hallucinogenic drugs such as LSD can be used to induce profoundly altered states of consciousness, and it is thus of interest to test the effects of these drugs on this system. 100 μg LSD was administrated orally to 20 healthy participants prior to fMRI assessment. Whole brain thalamic functional connectivity was measured using ROI-to-ROI and ROI-to-voxel approaches. Correlation analyses were used to explore relationships between thalamic connectivity to regions involved in auditory and visual hallucinations and subjective ratings on auditory and visual drug effects. LSD caused significant alterations in all dimensions of the 5D-ASC scale and significantly increased thalamic functional connectivity to various cortical regions. Furthermore, LSD-induced functional connectivity measures between the thalamus and the right fusiform gyrus and insula correlated significantly with subjective auditory and visual drug effects. Hallucinogenic drug effects might be provoked by facilitations of cortical excitability via thalamocortical interactions. Our findings have implications for the understanding of the mechanism of action of hallucinogenic drugs and provide further insight into the role of the 5-HT2A -receptor in altered states of consciousness. © 2017 The Authors Acta Psychiatrica Scandinavica Published by John Wiley & Sons Ltd.

  19. Sex differences in feeding behavior in rats: the relationship with neuronal activation in the hypothalamus

    Directory of Open Access Journals (Sweden)

    Atsushi eFukushima

    2015-03-01

    Full Text Available There is general agreement that the central nervous system in rodents differs between sexes due to the presence of gonadal steroid hormone during differentiation. Sex differences in feeding seem to occur among species, and responses to fasting (i.e., starvation, gonadal steroids (i.e., testosterone and estradiol, and diet (i.e., western-style diet vary significantly between sexes. The hypothalamus is the center for controlling feeding behavior. We examined the activation of feeding-related peptides in neurons in the hypothalamus. Phosphorylation of cyclic AMP response element-binding protein (CREB is a good marker for neural activation, as is the Fos antigen. Therefore, we predicted that sex differences in the activity of melanin-concentrating hormone (MCH neurons would be associated with feeding behavior. We determined the response of MCH neurons to glucose in the lateral hypothalamic area (LHA and our results suggested MCH neurons play an important role in sex differences in feeding behavior. In addition, fasting increased the number of orexin neurons harboring phosphorylated CREB in female rats (regardless of the estrous day, but not male rats. Glucose injection decreased the number of these neurons with phosphorylated CREB in fasted female rats. Finally, under normal spontaneous food intake, MCH neurons, but not orexin neurons, expressed phosphorylated CREB. These sex differences in response to fasting and glucose, as well as under normal conditions, suggest a vulnerability to metabolic challenges in females.

  20. Decreased thalamic glutamate level in unmedicated adult obsessive-compulsive disorder patients detected by proton magnetic resonance spectroscopy.

    Science.gov (United States)

    Zhu, Yajing; Fan, Qing; Han, Xu; Zhang, Haiyin; Chen, Jue; Wang, Zhen; Zhang, Zongfeng; Tan, Ling; Xiao, Zeping; Tong, Shanbao; Maletic-Savatic, Mirjana; Li, Yao

    2015-06-01

    Previous neuroimaging studies implied that the dysfunction of cortico-striato-thalamo-cortical (CSTC) circuit served as the neural basis for the pathophysiology of obsessive-compulsive disorder (OCD). The imbalances in neuronal metabolite and neurotransmitter within CSTC circuit have been shown as the leading reasons of the OCD onset. The aim of this study is to investigate the metabolic alterations, especially the glutamatergic signal dysfunction within CSTC circuit, and the relationships between neural metabolites and the symptom severity of OCD patients. Single voxel magnetic resonance spectroscopy (MRS) was conducted in medial prefrontal cortex (mPFC) and bilateral thalamus areas for thirteen unmedicated adult OCD patients with age-, gender-, and education-matched healthy controls. Quantification and multivariate analysis were performed to identify vital metabolic biomarkers for patients and healthy controls group differentiation. Moreover, we performed Spearman׳s rank correlation analysis for OCD patients to examine the relationship between the metabolite concentration level and OCD symptomatology. Patients with OCD showed significantly decreased glutamate level in mPFC (p=0.021) and right thalamus (p=0.039), and significantly increased choline compounds in left thalamus (p=0.044).The glutamate in right thalamus was shown as the most important metabolite for group separation from multivariate analysis (Q(2)=0.134) and was significantly correlated with the patients׳ compulsion scores (Spearman r=-0.674, p=0.016). Limited sample size, the use of creatine and phosphocreatine (Cr) ratios rather than absolute concentrations and unresolved glutamine (Gln) are limitations of the present study. Our study results consolidated the hypothesis about glutamatergic signaling dysfunction in OCD. To our knowledge, it is the first finding about a reduced thalamic glutamate level in adult unmedicated OCD patients. The dysregulation of glutamate serves as a potential target

  1. Regional thalamic neuropathology in patients with hippocampal sclerosis and epilepsy: A postmortem study

    Science.gov (United States)

    Sinjab, Barah; Martinian, Lillian; Sisodiya, Sanjay M; Thom, Maria

    2013-01-01

    Purpose Clinical, experimental, and neuroimaging data all indicate that the thalamus is involved in the network of changes associated with temporal lobe epilepsy (TLE), particularly in association with hippocampal sclerosis (HS), with potential roles in seizure initiation and propagation. Pathologic changes in the thalamus may be a result of an initial insult, ongoing seizures, or retrograde degeneration through reciprocal connections between thalamic and limbic regions. Our aim was to carry out a neuropathologic analysis of the thalamus in a postmortem (PM) epilepsy series, to assess the distribution, severity, and nature of pathologic changes and its association with HS. Methods Twenty-four epilepsy PM cases (age range 25–87 years) and eight controls (age range 38–85 years) were studied. HS was classified as unilateral (UHS, 11 cases), bilateral (BHS, 4 cases) or absent (No-HS, 9 cases). Samples from the left and right sides of the thalamus were stained with cresyl violet (CV), and for glial firbillary acidic protein (GFAP) and synaptophysin. Using image analysis, neuronal densities (NDs) or field fraction staining values (GFAP, synaptophysin) were measured in four thalamic nuclei: anteroventral nucleus (AV), lateral dorsal nucleus (LD), mediodorsal nucleus (MD), and ventrolateral nucleus (VL). The results were compared within and between cases. Key Findings The severity, nature, and distribution of thalamic pathology varied between cases. A pattern that emerged was a preferential involvement of the MD in UHS cases with a reduction in mean ND ipsilateral to the side of HS (p = 0.05). In UHS cases, greater field fraction values for GFAP and lower values for synaptophysin and ND were seen in the majority of cases in the MD ipsilateral to the side of sclerosis compared to other thalamic nuclei. In addition, differences in the mean ND between classical HS, atypical HS, and No-HS cases were noted in the ipsilateral MD (p < 0.05), with lower values observed in

  2. Development of involuntary movements after ventriculoperitoneal shunting for normal pressure hydrocephalus in a patient with chronic-phase thalamic haemorrhage.

    Science.gov (United States)

    Shindo, Keiichiro; Kondo, Takeo; Sugiyama, Ken; Nishijima, Kazunori; Furusawa, Yoshihito; Mori, Takayuki; Izumi, Shin-Ichi

    2007-10-01

    Delayed-onset involuntary movements have been described after thalamic stroke. We treated a patient with involuntary movements that increased after ventriculoperitoneal shunting (VPS) for normal pressure hydrocephalus (NPH) following thalamic haemorrage. One and one-half years after right thalamic and intraventricular haemorrhage, NPH suggested clinical evaluation and neuroimaging studies in a 56-year-old man. Hemidystonia and pseudochoreoathetosis were evident in the left arm, leg and trunk. Proprioceptive impairment and mild cerebellar dysfunction affected the left upper and lower extremity. Yet the patient could walk unassisted and carry out activities of daily living (ADL) rated as 90 points according to the Barthel Index (BI). Lumbar puncture lessened both gait disturbance and cognitive impairment. After VPS, cognition and urinary continence improved, but involuntary movements worsened, precluding unaided ambulation and decreasing the BI score to 65 points. Computed tomography after VPS showed resolution of NPH, while single-photon emission computed tomography showed increased cerebral blood flow after VPS. Increased cerebral blood flow after VPS is suspected to have promoted development of abnormal neuronal circuitry.

  3. Juxtasomal biocytin labeling to study the structure-function relationship of individual cortical neurons.

    Science.gov (United States)

    Narayanan, Rajeevan T; Mohan, Hemanth; Broersen, Robin; de Haan, Roel; Pieneman, Anton W; de Kock, Christiaan P J

    2014-02-25

    The cerebral cortex is characterized by multiple layers and many distinct cell-types that together as a network are responsible for many higher cognitive functions including decision making, sensory-guided behavior or memory. To understand how such intricate neuronal networks perform such tasks, a crucial step is to determine the function (or electrical activity) of individual cell types within the network, preferentially when the animal is performing a relevant cognitive task. Additionally, it is equally important to determine the anatomical structure of the network and the morphological architecture of the individual neurons to allow reverse engineering the cortical network. Technical breakthroughs available today allow recording cellular activity in awake, behaving animals with the valuable option of post hoc identifying the recorded neurons. Here, we demonstrate the juxtasomal biocytin labeling technique, which involves recording action potential spiking in the extracellular (or loose-patch) configuration using conventional patch pipettes. The juxtasomal recording configuration is relatively stable and applicable across behavioral conditions, including anesthetized, sedated, awake head-fixed, and even in the freely moving animal. Thus, this method allows linking cell-type specific action potential spiking during animal behavior to reconstruction of the individual neurons and ultimately, the entire cortical microcircuit. In this video manuscript, we show how individual neurons in the juxtasomal configuration can be labeled with biocytin in the urethane-anaesthetized rat for post hoc identification and morphological reconstruction.

  4. Global suppression of electrocortical activity in unilateral perinatal thalamic stroke.

    LENUS (Irish Health Repository)

    Kharoshankaya, Liudmila

    2014-07-01

    We present an unusual case of persistent generalized electroencephalography (EEG) suppression and right-sided clonic seizures in a male infant born at 40(+2) weeks\\' gestation, birthweight 3240g, with an isolated unilateral thalamic stroke. The EEG at 13 hours after birth showed a generalized very low amplitude background pattern, which progressed to frequent electrographic seizures over the left hemisphere. The interictal background EEG pattern remained grossly abnormal over the next 48 hours, showing very low background amplitudes (<10μV). Magnetic resonance imaging revealed an isolated acute left-sided thalamic infarction. This is the first description of severe global EEG suppression caused by an isolated unilateral thalamic stroke and supports the role of the thalamus as the control centre for cortical electrical activity.

  5. Bilateral thalamic infarction with psychiatric symptoms: case report

    Directory of Open Access Journals (Sweden)

    Betül Tekin Güveli

    2016-04-01

    Full Text Available Introduction: Thalamus is a mass of gray matter, which plays a role in the transmission of sensory and motor information to the primary sensory and motor centers of the cerebral cortex, cerebellum and basal ganglia. Vascular lesions of thalamus may occur in different syndromes depending on the affected nuclei. In this report, a case with acute evolving personality and behavior changes and detected bilateral thalamic infarction will be presented. Case: A 40-year-old male patient was brought to the psychiatric ER with complaints of acute excessive sleep and behavioral changing. His neurological examination was normal except for limited cooperation and dysarthria. There was hyperintensity in bilateral paramedian thalamic regions in diffusion MRI and hypointensity in the right side in the ADC. During clinical observation the patient occasionally had visual hallucinations and attempted suicide. The psychiatrist diagnosed the patient with psychotic disorder due to his general medical condition and olanzapine 10 mg / day was prescribed. Etiological tests were normal. The patient was discharged after clinical improvement on the tenth day of hospitalization. Conclusion: Bilateral thalamic infarcts are very rare in all ischemic cerebrovascular diseases and typically result in changing of consciousness, gaze palsy and memory. The most common etiological cause of bilateral thalamic infarct is cardioembolism and the prognosis is generally good. Thalamic infarcts have a clinical spectrum varying according to the location of the lesion and may even just be present with psychiatric symptoms. In acute or subacute personality and behavior changes in a patient with no history of psychiatric disorders, thalamic lesions should be considered.

  6. Bilateral paramedian thalamic artery infarcts: report of 10 cases.

    Science.gov (United States)

    Jiménez Caballero, Pedro Enrique

    2010-01-01

    The paramedian thalamic arteries can arise as a pair from each P1 of the posterior cerebral artery, but they may also arise equally from a common trunk off one P1, thus supplying thalamus bilaterally. Such a common trunk is called the artery of Percheron and supplies the mesial aspects of both thalami and the rostral midbrain. This is a retrospective review of 1,253 consecutive patients with ischemic stroke enrolled in a stroke registry within an 8-year period (January 2001-December 2008). All were evaluated with detailed clinical and neuropsychological evaluation, magnetic resonance imaging (MRI), blood studies, electrocardiogram, and transthoracic echocardiography. All standard risk factors were recorded in these patients. Ten patients (0.7%) in this series presented with a first-ever thalamic stroke demonstrating bilateral paramedian thalamic lesions on MRI. The main cause of bilateral paramedian thalamic infarctions was small artery disease (60%), followed by cardioembolism (40%). A well-defined clinical picture is shown in bilateral paramedian thalamic artery infarcts. These patients had disorder's consisting of consciousness, memory dysfunctions, various types of vertical gaze paresis, and psychological changes. Although neurologic deficits and hypersomnia recovered to large extent in patients with paramedian thalamic infarcts, cognitive deficits that were mainly linked with bilateral and left-sided lesions often persisted. Vertical gaze paresis tended to improve and never seriously disturbed the patient's activities. We believe that these kinds of strokes have been commonly overlooked, especially without widespread use of MRI. Copyright (c) 2010 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  7. Relationships between dendritic morphology, spatial distribution and firing patterns in rat layer 1 neurons

    Directory of Open Access Journals (Sweden)

    D.V.V. Santos

    2012-12-01

    Full Text Available The cortical layer 1 contains mainly small interneurons, which have traditionally been classified according to their axonal morphology. The dendritic morphology of these cells, however, has received little attention and remains ill defined. Very little is known about how the dendritic morphology and spatial distribution of these cells may relate to functional neuronal properties. We used biocytin labeling and whole cell patch clamp recordings, associated with digital reconstruction and quantitative morphological analysis, to assess correlations between dendritic morphology, spatial distribution and membrane properties of rat layer 1 neurons. A total of 106 cells were recorded, labeled and subjected to morphological analysis. Based on the quantitative patterns of their dendritic arbor, cells were divided into four major morphotypes: horizontal, radial, ascendant, and descendant cells. Descendant cells exhibited a highly distinct spatial distribution in relation to other morphotypes, suggesting that they may have a distinct function in these cortical circuits. A significant difference was also found in the distribution of firing patterns between each morphotype and between the neuronal populations of each sublayer. Passive membrane properties were, however, statistically homogeneous among all subgroups. We speculate that the differences observed in active membrane properties might be related to differences in the synaptic input of specific types of afferent fibers and to differences in the computational roles of each morphotype in layer 1 circuits. Our findings provide new insights into dendritic morphology and neuronal spatial distribution in layer 1 circuits, indicating that variations in these properties may be correlated with distinct physiological functions.

  8. Orthostatic tremor responds to bilateral thalamic deep brain stimulation.

    Science.gov (United States)

    Lyons, Mark K; Behbahani, Mandana; Boucher, Orland K; Caviness, John N; Evidente, Virgilio Gerald H

    2012-01-01

    Orthostatic tremor (OT) is a disabling movement disorder manifested by postural and gait disturbance. Primarily a condition of elderly people, it can be progressive in up to 15% of patients. The primary treatments are medications that are often ineffective. A 75-year-old male presented with a 10-year history of progressive and disabling OT. He had tried various medications without significant benefits. He underwent bilateral thalamic Vim deep brain stimulation (DBS). At 30-month follow-up, he has had continued significant improvement of his OT. Bilateral thalamic DBS may be a viable option for medically refractory OT.

  9. Thalamic syndrome as the heralding manifestation of atlantoaxial dislocation

    Science.gov (United States)

    Verma, Rajesh; Sahu, Ritesh; Ojha, B K; Junewar, Vivek

    2013-01-01

    In India, Atlantoaxial dislocation (AAD) is the commonest skeletal craniovertebral junction (CVJ) anomaly, followed by occipitalisation of atlas and basilar invagination. The usual presentation is progressive neurological deficit (76–95% cases) involving the high cervical cord, lower brainstem and cranial nerves. The association between vertebro-basilar insufficiency and skeletal CVJ anomalies is well recognised and angiographic abnormalities of the vertebrobasilar arteries and their branches have been reported; however, initial presentation of CVJ anomaly as thalamic syndrome due to posterior circulation stroke is extremely rare. Here, we report one such rare case of thalamic syndrome as the initial presentation of CVJ anomaly with AAD. PMID:23314448

  10. Deep brain stimulation of the mediodorsal thalamic nucleus yields increases in the expression of zif-268 but not c-fos in the frontal cortex.

    Science.gov (United States)

    Ewing, Samuel G; Porr, Bernd; Pratt, Judith A

    2013-09-01

    This study explores the regions activated by deep brain stimulation of the mediodorsal thalamic nucleus through examination of immediate early genes as markers of neuronal activation. Stimulation was delivered unilaterally with constant current 100 μs duration pulses at a frequency of 130 Hz delivered at an amplitude of 200 μA for 3h. Brains were removed, sectioned and radio-labelled for the IEGs zif-268 and c-fos. In anaesthetised rats, deep brain stimulation of mediodorsal thalamic nucleus produced robust increases in the expression of zif-268 but not c-fos localised to regions that are reciprocally connected with the mediodorsal thalamic nucleus, including the prelimbic and orbitofrontal cortices, and the premotor cortex indicating an increase in synaptic activity in these regions. These findings map those brain regions that are persistently, rather than transiently, activated by high frequency electrical stimulation of the mediodorsal thalamic nucleus by a putatively antidromic mechanism which may be relevant to neuropsychiatric disorders such as schizophrenia in which thalamocortical systems are disrupted and in which DBS protocols are being considered. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Thalamic theta phase alignment predicts human memory formation and anterior thalamic cross-frequency coupling.

    Science.gov (United States)

    Sweeney-Reed, Catherine M; Zaehle, Tino; Voges, Jürgen; Schmitt, Friedhelm C; Buentjen, Lars; Kopitzki, Klaus; Hinrichs, Hermann; Heinze, Hans-Jochen; Rugg, Michael D; Knight, Robert T; Richardson-Klavehn, Alan

    2015-05-20

    Previously we reported electrophysiological evidence for a role for the anterior thalamic nucleus (ATN) in human memory formation (Sweeney-Reed et al., 2014). Theta-gamma cross-frequency coupling (CFC) predicted successful memory formation, with the involvement of gamma oscillations suggesting memory-relevant local processing in the ATN. The importance of the theta frequency range in memory processing is well-established, and phase alignment of oscillations is considered to be necessary for synaptic plasticity. We hypothesized that theta phase alignment in the ATN would be necessary for memory encoding. Further analysis of the electrophysiological data reveal that phase alignment in the theta rhythm was greater during successful compared with unsuccessful encoding, and that this alignment was correlated with the CFC. These findings support an active processing role for the ATN during memory formation.

  12. Modulation of sensitivity to alcohol by cortical and thalamic brain regions.

    Science.gov (United States)

    Jaramillo, Anel A; Randall, Patrick A; Frisbee, Suzanne; Besheer, Joyce

    2016-10-01

    The nucleus accumbens core (AcbC) is a key brain region known to regulate the discriminative stimulus/interoceptive effects of alcohol. As such, the goal of the present work was to identify AcbC projection regions that may also modulate sensitivity to alcohol. Accordingly, AcbC afferent projections were identified in behaviorally naïve rats using a retrograde tracer which led to the focus on the medial prefrontal cortex (mPFC), insular cortex (IC) and rhomboid thalamic nucleus (Rh). Next, to examine the possible role of these brain regions in modulating sensitivity to alcohol, neuronal response to alcohol in rats trained to discriminate alcohol (1 g/kg, intragastric [IG]) vs. water was examined using a two-lever drug discrimination task. As such, rats were administered water or alcohol (1 g/kg, IG) and brain tissue was processed for c-Fos immunoreactivity (IR), a marker of neuronal activity. Alcohol decreased c-Fos IR in the mPFC, IC, Rh and AcbC. Lastly, site-specific pharmacological inactivation with muscimol + baclofen (GABAA agonist + GABAB agonist) was used to determine the functional role of the mPFC, IC and Rh in modulating the interoceptive effects of alcohol in rats trained to discriminate alcohol (1 g/kg, IG) vs. water. mPFC inactivation resulted in full substitution for the alcohol training dose, and IC and Rh inactivation produced partial alcohol-like effects, demonstrating the importance of these regions, with known projections to the AcbC, in modulating sensitivity to alcohol. Together, these data demonstrate a site of action of alcohol and the recruitment of cortical/thalamic regions in modulating sensitivity to the interoceptive effects of alcohol. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  13. Sleep-potentiated epileptiform activity in early thalamic injuries: Study in a large series (60 cases).

    Science.gov (United States)

    Losito, Emma; Battaglia, Domenica; Chieffo, Daniela; Raponi, Matteo; Ranalli, Domiziana; Contaldo, Ilaria; Giansanti, Cristina; De Clemente, Valentina; Quintiliani, Michela; Antichi, Eleonora; Verdolotti, Tommaso; de Waure, Chiara; Tartaglione, Tommaso; Mercuri, Eugenio; Guzzetta, Francesco

    2015-01-01

    The study aims at a better definition of continuous spike-waves during sleep (CSWS) with an early thalamic lesion, focusing on various grades of sleep-potentiated epileptiform activity (SPEA). Their possible relationship with different clinical features was studied to try to define prognostic factors of the epileptic disorder, especially relating to behavior/cognitive outcome, in order to improve prevention and treatment strategies. Sixty patients with early thalamic injury were followed since the first registration of SPEA with serial neurological, long term EEG monitoring and neuropsychological examinations, as well as neuroimaging and a detailed clinical history. They were classified in three different groups according to the sleep spike-waves (SW) quantification: electrical status epilepticus during sleep (ESES), more than 85% of slow sleep; overactivation between 50% and 85% and simple activation between 10 and 50%). Results were then examined also with a statistical analysis. In our series of CSWS occurring in early brain injured children with unilateral thalamic involvement there is a common neuropathologic origin but with various grades of SPEA severity. Statistical analysis showed that patients evolving toward ESES presented more commonly the involvement of the mediodorsal part of thalamus nuclei and a bilateral cortico-subcortical brain injury, epilepsy was more severe with a delayed onset; moreover, in the acute stage .ESES patients presented the worst behavior/cognitive performances. As to cognitive and behavior outcome, longer SPEA duration as well as bilateral brain injury and cognitive/behavior impairment in acute phase appear linked to a poor outcome; some particular neuropathology (ischemic stroke and haemorrhagic infarction) as well as hydrocephalus shunting are associated with behavior disorders. Discrete features seem to support different underlying mechanisms in ESES patients in comparison with less severe SPEA; they represent negative

  14. mGluR-mediated calcium signalling in the thalamic reticular nucleus.

    Science.gov (United States)

    Neyer, Christina; Herr, David; Kohmann, Denise; Budde, Thomas; Pape, Hans-Christian; Coulon, Philippe

    2016-06-01

    The thalamic reticular nucleus (TRN) plays a major role in modulating the transfer of information from the thalamus to the cortex. GABAergic inhibition via the TRN is differentially regulated by metabotropic glutamate receptors (mGluRs) and the effect of mGluRs on the membrane potential, on ion channels, and on the plasticity of electrical coupling of TRN neurons has been studied previously. Although mGluRs are generally known to trigger Ca(2+) transients, mGluR-mediated Ca(2+)-transients in TRN neurons have not yet been investigated. In this study, we show that mGluRs can trigger Ca(2+)-transients in TRN neurons, that these transients depend on intracellular Ca(2+)-stores, and are mediated by IP3 receptors. Ca(2+) transients caused by the group I mGluR agonist DHPG elicit a current that is sensitive to flufenamic acid and has a reversal potential around -40mV. Our results add mGluR-mediated Ca(2+)-signalling in the TRN to the state-dependent modulators of the thalamocortical system. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Thalamic abscess caused by a rare pathogen: streptococcus ...

    African Journals Online (AJOL)

    Streptococcus constellatus is a microorganism that lives commensally in the oropharyngeal region, urogenital region, and intestinal tract. However, it can cause infection in patients with certain predisposing factors. Rarely, this microorganism can cause a brain abscess. Thalamic localization of brain abscesses is much rarer ...

  16. Neuroanatomical considerations of isolated hearing loss in thalamic hemorrhage

    Directory of Open Access Journals (Sweden)

    Nitin Agarwal, M.D.

    2016-12-01

    Conclusion: Presumably, this neurological deficit was caused by a hypertensive hemorrhage in the posterior right thalamus. The following case and discussion will review the potential neuroanatomical pathways that we suggest could make isolated hearing loss be part of a “thalamic syndrome.”

  17. Effects of Intralaminar Thalamic Stimulation on Language Functions

    Science.gov (United States)

    Bhatnagar, Subhash C.; Mandybur, George T.

    2005-01-01

    Fifteen neurosurgical subjects, who were undergoing thalamic chronic electrode implants as a treatment for dyskinesia and chronic pain, were evaluated on a series of neurolinguistic functions to determine if the stimulation of the centromedianum nucleus of the thalamus affected language and cognitive processing. Analysis of the data revealed that…

  18. Hypertensive thalamic hemorrhage. Clinical symptoms and outcomes in 40 cases

    Energy Technology Data Exchange (ETDEWEB)

    Munaka, Masahiro; Nishikawa, Michio; Hirai, Osamu; Kaneko, Takaaki; Watanabe, Syu; Fukuma, Jun; Handa, Hajime

    1988-12-01

    In the past six years, we have had experience with 40 patients with hypertensive thalamic hemorrhages, as verified by CT scan at our hospital within 24 hours. These patients were classified into the following three groups according to the location of the bleeding point and the size of the hematoma: (1) anteromedial (4 cases), (2) posterolateral (16 cases), and (3) massive (20 cases). The (1) and (2) hematomas were small (less than 3 cm in diameter), while those in (3) were large (more than 3 cm in diameter). Twenty cases (50% of all the thalamic hematomas) were small hematomas. The characteristic clinical symptoms of the anteromedial type were a mild disturbance of consciousness and thalamic dementia, while those of the posterolateral type were motor and sensory disturbance, and thalamic aphasia, respectively. Twenty cases (50%) were large hematomas. The clinical symptoms of these cases were mainly consciousness disturbance; 7 of them expired. Based on this experience, it may be considered that the patients whose hematoma size was larger than 3 cm had a poor prognosis and that the patients with the posterolateral type had a poor functional diagnosis.

  19. Open-loop organization of thalamic reticular nucleus and dorsal thalamus: a computational model.

    Science.gov (United States)

    Willis, Adam M; Slater, Bernard J; Gribkova, Ekaterina D; Llano, Daniel A

    2015-10-01

    The thalamic reticular nucleus (TRN) is a shell of GABAergic neurons that surrounds the dorsal thalamus. Previous work has shown that TRN neurons send GABAergic projections to thalamocortical (TC) cells to form reciprocal, closed-loop circuits. This has led to the hypothesis that the TRN is responsible for oscillatory phenomena, such as sleep spindles and absence seizures. However, there is emerging evidence that open-loop circuits are also found between TRN and TC cells. The implications of open-loop configurations are not yet known, particularly when they include time-dependent nonlinearities in TC cells such as low-threshold bursting. We hypothesized that low-threshold bursting in an open-loop circuit could be a mechanism by which the TRN could paradoxically enhance TC activation, and that enhancement would depend on the relative timing of TRN vs. TC cell stimulation. To test this, we modeled small circuits containing TC neurons, TRN neurons, and layer 4 thalamorecipient cells in both open- and closed-loop configurations. We found that open-loop TRN stimulation, rather than universally depressing TC activation, increased cortical output across a broad parameter space, modified the filter properties of TC neurons, and altered the mutual information between input and output in a frequency-dependent and T-type calcium channel-dependent manner. Therefore, an open-loop model of TRN-TC interactions, rather than suppressing transmission through the thalamus, creates a tunable filter whose properties may be modified by outside influences onto the TRN. These simulations make experimentally testable predictions about the potential role for the TRN for flexible enhancement of cortical activation. Copyright © 2015 the American Physiological Society.

  20. Noradrenergic transmission in the central medial thalamic nucleus modulates the electroencephalographic activity and emergence from propofol anesthesia in rats.

    Science.gov (United States)

    Fu, Bao; Yu, Tian; Yuan, Jie; Gong, Xingrui; Zhang, Mazhong

    2017-03-01

    At present, the mechanisms by which general anesthetics causing loss of consciousness remain unclear. The central medial thalamic nucleus (CMT) is a rarely studied component of the midline thalamic complex, which is deemed to be a part of the nonspecific arousal system. Although the CMT participates in modulating arousal and receives excitatory noradrenergic projections from locus coeruleus, it remains unknown whether the noradrenergic pathway in the CMT takes part in modulating the arousal system. Therefore, we hypothesized that noradrenergic transmission in the CMT is involved in modulating induction and emergence of propofol anesthesia. First, we infused norepinephrine (NE) into the CMT to observe the role of CMT noradrenergic pathway in modulating the anesthetic state induced by propofol. The results showed that microinjection of NE into the CMT accelerated emergence from propofol anesthesia, but had no impact on the induction of or sensitivity to propofol anesthesia in rats. In addition, infusion of NE into the CMT caused electroencephalography changes in the prefrontal cortex and the anterior cingulate cortex. Finally, we used a whole-cell patch clamp to examine the effects of NE on neuronal excitability and GABAergic transmission in the CMT. In the CMT slices, propofol suppressed neuronal excitability and enhanced GABAergic transmission, while application of NE partly reversed these effects. These findings support the hypothesis that the CMT noradrenergic pathway plays an important role in modulating the emergence from general anesthesia. © 2017 International Society for Neurochemistry.

  1. Childhood maltreatment is associated with larger left thalamic gray matter volume in adolescents with generalized anxiety disorder.

    Directory of Open Access Journals (Sweden)

    Mei Liao

    Full Text Available BACKGROUND: Generalized anxiety disorder (GAD is a common anxiety disorder that usually begins in adolescence. Childhood maltreatment is highly prevalent and increases the possibility for developing a variety of mental disorders including anxiety disorders. An earlier age at onset of GAD is significantly related to maltreatment in childhood. Exploring the underpinnings of the relationship between childhood maltreatment and adolescent onset GAD would be helpful in identifying the potential risk markers of this condition. METHODS: Twenty-six adolescents with GAD and 25 healthy controls participated in this study. A childhood trauma questionnaire (CTQ was introduced to assess childhood maltreatment. All subjects underwent high-resolution structural magnetic resonance scans. Voxel-based morphometry (VBM was used to investigate gray matter alterations. RESULTS: Significantly larger gray matter volumes of the right putamen were observed in GAD patients compared to healthy controls. In addition, a significant diagnosis-by-maltreatment interaction effect for the left thalamic gray matter volume was revealed, as shown by larger volumes of the left thalamic gray matter in GAD patients with childhood maltreatment compared with GAD patients without childhood maltreatment as well as with healthy controls with/without childhood maltreatment. A significant positive association between childhood maltreatment and left thalamic gray matter volume was only seen in GAD patients. CONCLUSIONS: These findings revealed an increased volume in the subcortical regions in adolescent GAD, and the alterations in the left thalamus might be involved in the association between childhood maltreatment and the occurrence of GAD.

  2. Medial thalamic 18-FDG uptake following inescapable shock correlates with subsequent learned helpless behavior

    Energy Technology Data Exchange (ETDEWEB)

    Mirrione,M.M.; Mirrione, M.M.; Schulz, D.; Dewey, S.L.; Henn, F.A.

    2009-12-06

    correlations were found in additional regions analyzed including the nucleus accumbens, caudate putamen, substantia nigra, and amygdala. These data suggest that medial thalamic 18-FDG uptake during inescapable shock may contribute to subsequent escape deficits, and are not confounded by shock effects per se, since all animals received the same treatment prior to scanning. We have previously explored 18-FDG differences following the escape test session which also showed hyperactivity in the medial thalamus of learned helpless animals compared to non-learned helpless, and included additional cortical-limbic changes. Given the neuroanatomical connections between the medial thalamus (and habenula) with the prefrontal cortex and monoaminergic brain stem, one possible speculation is that abnormal neuronal activity in these areas during stress may set in motion circuitry changes that correlate with learned helpless behavior.

  3. Sleep onset uncovers thalamic abnormalities in patients with idiopathic generalised epilepsy

    Directory of Open Access Journals (Sweden)

    Andrew P. Bagshaw

    2017-01-01

    Full Text Available The thalamus is crucial for sleep regulation and the pathophysiology of idiopathic generalised epilepsy (IGE, and may serve as the underlying basis for the links between the two. We investigated this using EEG-fMRI and a specific emphasis on the role and functional connectivity (FC of the thalamus. We defined three types of thalamic FC: thalamocortical, inter-hemispheric thalamic, and intra-hemispheric thalamic. Patients and controls differed in all three measures, and during wakefulness and sleep, indicating disorder-dependent and state-dependent modification of thalamic FC. Inter-hemispheric thalamic FC differed between patients and controls in somatosensory regions during wakefulness, and occipital regions during sleep. Intra-hemispheric thalamic FC was significantly higher in patients than controls following sleep onset, and disorder-dependent alterations to FC were seen in several thalamic regions always involving somatomotor and occipital regions. As interactions between thalamic sub-regions are indirect and mediated by the inhibitory thalamic reticular nucleus (TRN, the results suggest abnormal TRN function in patients with IGE, with a regional distribution which could suggest a link with the thalamocortical networks involved in the generation of alpha rhythms. Intra-thalamic FC could be a more widely applicable marker beyond patients with IGE.

  4. Altered thalamic connectivity during spontaneous attacks of migraine without aura

    DEFF Research Database (Denmark)

    Amin, Faisal Mohammad; Hougaard, Anders; Magon, Stefano

    2017-01-01

    Background Functional connectivity of brain networks may be altered in migraine without aura patients. Functional magnetic resonance imaging (fMRI) studies have demonstrated changed activity in the thalamus, pons and cerebellum in migraineurs. Here, we investigated the thalamic, pontine and cereb......Background Functional connectivity of brain networks may be altered in migraine without aura patients. Functional magnetic resonance imaging (fMRI) studies have demonstrated changed activity in the thalamus, pons and cerebellum in migraineurs. Here, we investigated the thalamic, pontine...... and cerebellar network connectivity during spontaneous migraine attacks. Methods Seventeen patients with episodic migraine without aura underwent resting-state fMRI scan during and outside of a spontaneous migraine attack. Primary endpoint was a difference in functional connectivity between the attack...

  5. Pseudocortical and dissociate discriminative sensory dysfunction in a thalamic stroke.

    Science.gov (United States)

    Notturno, Francesca; Sepe, Rosamaria; Caulo, Massimo; Uncini, Antonino; Committeri, Giorgia

    2013-01-01

    In thalamic lesions a pseudocortical syndrome has been occasionally described but the effect of the lesion on the cortical network of tactile recognition has never been studied. We report a patient who developed tactile agnosia in the left hand after right thalamic stroke, configuring a pseudocortical sensory syndrome. The discriminative sensory dysfunction was dissociate because only tactile agnosia and mild pseudoathetosis were present. A functional magnetic resonance imaging (fMRI) study showed that tactile recognition with the unaffected hand recruited a bilateral fronto-parietal network. During recognition with the left hand the activation was restricted and lateralized to the ipsilateral hemisphere. In this patient with pseudocortical discriminative sensory dysfunction the lack of activation of the whole cortical network, implicated in tactile recognition, demonstrates that pseudocortical is functionally equivalent to cortical tactile agnosia. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Differential diagnosis of bilateral thalamic lesions; Differenzialdiagnose bilateral Thalamuslaesionen

    Energy Technology Data Exchange (ETDEWEB)

    Linn, J.; Brueckmann, H. [Universitaetsklinikum Muenchen (Germany). Abt. fuer Neuroradiologie; Hoffmann, L.A. [Universitaetsklinikum Muenchen (Germany). Inst. fuer Klinische Neuroimmunologie; Danek, A. [Universitaetsklinikum Muenchen (Germany). Klinik und Poliklinik fuer Neurologie

    2007-03-15

    A multitude of different diseases can result in bilateral thalamic lesions. These include vascular pathologies requiring prompt therapeutic intervention, such as basilar thrombosis or thrombosis of the internal cerebral veins, as well as tumors, infectious or demyelinating diseases, and toxic-metabolic lesions. Therefore, detailed knowledge of the typical radiological findings for the various diseases is essential for determining the correct diagnosis. This review provides a synopsis of the radiological findings for the most important bithalamic lesions and an overview of the literature.

  7. Injury of the mammillothalamic tract in patients with thalamic hemorrhage

    Directory of Open Access Journals (Sweden)

    Hyeok Gyu eKwon

    2014-04-01

    Full Text Available Objective:Injury of the mammillothalamic tract(MTT has been suggested as one of the plausible pathogenic mechanisms of memory impairment in patients with thalamic hemorrhage; however, it has not been clearly demonstrated so far. We attempted to investigate whether injury of the MTT documented by diffusion tensor tractography(DTT following thalamic hemorrhage correlates with cognitive impairment. Methods:We recruited 22 patients with a thalamic hemorrhage and 20 control subjects. MTTs were reconstructed using the probabilistic tractography method. Patients were classified into two subgroups: Reconstructed group-patients whose MTT was reconstructed in the affected hemisphere and Non-reconstructed group-patients whose MTT was not reconstructed.Results:MTT was reconstructed in five(22.7%,Reconstructed group patients in the affected hemisphere and was not reconstructed in the remaining 17 patients(77.3%,Non-reconstructed group. In addition, the MTT was not reconstructed even in the unaffected hemisphere in four patients(23.5% in Non-reconstructed group. Fractional anisotropy and mean diffusivity values of the affected hemisphere in Reconstructed group also did not show significant differences from those in the unaffected hemisphere of Reconstructed group and the control group(p>0.05. However, the tract volume of the affected hemisphere in Reconstructed group was significantly lower than that of the unaffected hemisphere in Reconstructed group and the control group(pConclusion:A large portion of patients with thalamic hemorrhage appeared to suffer severe injury of the ipsi-lesional MTT(77.3% and 18.2% of these patients appeared to suffer severe injury even in the contra-lesional MTT. In addition, the remaining 22.7% of patients who had preserved integrity of the ipsi-lesional MTT appeared to suffer partial injury of the ipsi-lesional MTT.

  8. Decrease of thalamic gray matter following limb amputation.

    Science.gov (United States)

    Draganski, B; Moser, T; Lummel, N; Gänssbauer, S; Bogdahn, U; Haas, F; May, A

    2006-07-01

    Modern neuroscience has elucidated general mechanisms underlying the functional plasticity of the adult mammalian brain after limb deafferentation. However, little is known about possible structural alterations following amputation and chronic loss of afferent input in humans. Using voxel-based morphometry (VBM), based on high-resolution magnetic resonance images, we investigated the brain structure of 28 volunteers with unilateral limb amputation and compared them to healthy controls. Subjects with limb amputation exhibited a decrease in gray matter of the posterolateral thalamus contralateral to the side of the amputation. The thalamic gray matter differences were positively correlated with the time span after the amputation but not with the frequency or magnitude of coexisting phantom pain. Phantom limb pain was unrelated to thalamic structural variations, but was positively correlated to a decrease in brain areas related to the processing of pain. No gray matter increase was detected. The unilateral thalamic differences may reflect a structural correlate of the loss of afferent input as a secondary change following deafferentation.

  9. Joint cross-correlation analysis reveals complex, time-dependent functional relationship between cortical neurons and arm electromyograms

    Science.gov (United States)

    Zhuang, Katie Z.; Lebedev, Mikhail A.

    2014-01-01

    Correlation between cortical activity and electromyographic (EMG) activity of limb muscles has long been a subject of neurophysiological studies, especially in terms of corticospinal connectivity. Interest in this issue has recently increased due to the development of brain-machine interfaces with output signals that mimic muscle force. For this study, three monkeys were implanted with multielectrode arrays in multiple cortical areas. One monkey performed self-timed touch pad presses, whereas the other two executed arm reaching movements. We analyzed the dynamic relationship between cortical neuronal activity and arm EMGs using a joint cross-correlation (JCC) analysis that evaluated trial-by-trial correlation as a function of time intervals within a trial. JCCs revealed transient correlations between the EMGs of multiple muscles and neural activity in motor, premotor and somatosensory cortical areas. Matching results were obtained using spike-triggered averages corrected by subtracting trial-shuffled data. Compared with spike-triggered averages, JCCs more readily revealed dynamic changes in cortico-EMG correlations. JCCs showed that correlation peaks often sharpened around movement times and broadened during delay intervals. Furthermore, JCC patterns were directionally selective for the arm-reaching task. We propose that such highly dynamic, task-dependent and distributed relationships between cortical activity and EMGs should be taken into consideration for future brain-machine interfaces that generate EMG-like signals. PMID:25210153

  10. Thalamic Spindles Promote Memory Formation during Sleep through Triple Phase-Locking of Cortical, Thalamic, and Hippocampal Rhythms.

    Science.gov (United States)

    Latchoumane, Charles-Francois V; Ngo, Hong-Viet V; Born, Jan; Shin, Hee-Sup

    2017-07-19

    While the interaction of the cardinal rhythms of non-rapid-eye-movement (NREM) sleep-the thalamo-cortical spindles, hippocampal ripples, and the cortical slow oscillations-is thought to be critical for memory consolidation during sleep, the role spindles play in this interaction is elusive. Combining optogenetics with a closed-loop stimulation approach in mice, we show here that only thalamic spindles induced in-phase with cortical slow oscillation up-states, but not out-of-phase-induced spindles, improve consolidation of hippocampus-dependent memory during sleep. Whereas optogenetically stimulated spindles were as efficient as spontaneous spindles in nesting hippocampal ripples within their excitable troughs, stimulation in-phase with the slow oscillation up-state increased spindle co-occurrence and frontal spindle-ripple co-occurrence, eventually resulting in increased triple coupling of slow oscillation-spindle-ripple events. In-phase optogenetic suppression of thalamic spindles impaired hippocampus-dependent memory. Our results suggest a causal role for thalamic sleep spindles in hippocampus-dependent memory consolidation, conveyed through triple coupling of slow oscillations, spindles, and ripples. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Dispersion of the intrinsic neuronal periods affects the relationship of the entrainment range to the coupling strength in the suprachiasmatic nucleus

    Science.gov (United States)

    Gu, Changgui; Yang, Huijie; Wang, Man

    2017-11-01

    Living beings on the Earth are subjected to and entrained (synchronized) to the natural 24-h light-dark cycle. Interestingly, they can also be entrained to an external artificial cycle of non-24-h periods. The range of these periods is called the entrainment range and it differs among species. In mammals, the entrainment range is regulated by a main clock located in the suprachiasmatic nucleus (SCN) which is composed of 10 000 neurons in the brain. Previous works have found that the entrainment range depends on the cellular coupling strength in the SCN. In particular, the entrainment range decreases with the increase of the cellular coupling strength, provided that all the neuronal oscillators are identical. However, the SCN neurons differ in the intrinsic periods that follow a normal distribution in a range from 22 to 28 h. In the present study, taking the dispersion of the intrinsic neuronal periods into account, we examined the relationship between the entrainment range and the coupling strength. Results from numerical simulations and theoretical analyses both show that the relationship is altered to be paraboliclike if the intrinsic neuronal periods are nonidentical, and the maximal entrainment range is obtained with a suitable coupling strength. Our results shed light on the role of the cellular coupling in the entrainment ability of the SCN network.

  12. Engineering a thalamo-cortico-thalamic circuit on SpiNNaker: a preliminary study toward modeling sleep and wakefulness.

    Science.gov (United States)

    Bhattacharya, Basabdatta S; Patterson, Cameron; Galluppi, Francesco; Durrant, Simon J; Furber, Steve

    2014-01-01

    We present a preliminary study of a thalamo-cortico-thalamic (TCT) implementation on SpiNNaker (Spiking Neural Network architecture), a brain inspired hardware platform designed to incorporate the inherent biological properties of parallelism, fault tolerance and energy efficiency. These attributes make SpiNNaker an ideal platform for simulating biologically plausible computational models. Our focus in this work is to design a TCT framework that can be simulated on SpiNNaker to mimic dynamical behavior similar to Electroencephalogram (EEG) time and power-spectra signatures in sleep-wake transition. The scale of the model is minimized for simplicity in this proof-of-concept study; thus the total number of spiking neurons is ≈1000 and represents a "mini-column" of the thalamocortical tissue. All data on model structure, synaptic layout and parameters is inspired from previous studies and abstracted at a level that is appropriate to the aims of the current study as well as computationally suitable for model simulation on a small 4-chip SpiNNaker system. The initial results from selective deletion of synaptic connectivity parameters in the model show similarity with EEG power spectra characteristics of sleep and wakefulness. These observations provide a positive perspective and a basis for future implementation of a very large scale biologically plausible model of thalamo-cortico-thalamic interactivity-the essential brain circuit that regulates the biological sleep-wake cycle and associated EEG rhythms.

  13. Engineering a thalamo-cortico-thalamic circuit on SpiNNaker: a preliminary study towards modelling sleep and wakefulness

    Directory of Open Access Journals (Sweden)

    Basabdatta Sen Bhattacharya

    2014-05-01

    Full Text Available We present a preliminary study of a thalamo-cortico-thalamic (TCT implementation on SpiNNaker (Spiking Neural Network architecture, a brain inspired hardware platform designed to incorporate the inherent biological properties of parallelism, fault tolerance and energy efficiency. These attributes make SpiNNaker an ideal platform for simulating biologically plausible computational models. Our focus in this work is to design a TCT framework that can be simulated on SpiNNaker to mimic dynamical behaviour similar to Electroencephalogram (EEG time and power-spectra signatures in sleep-wake transition. The scale of the model is minimised for simplicity in this proof-of-concept study; thus the total number of spiking neurons is approximately 1000 and represents a `mini-column' of the thalamocortical tissue. All data on model structure, synaptic layout and parameters is inspired from previous studies and abstracted at a level that is appropriate to the aims of the current study as well as computationally suitable for model simulation on a small 4-chip SpiNNaker system. The initial results from selective deletion of synaptic connectivity parameters in the model show similarity with EEG time series characteristics of sleep and wakefulness. These observations provide a positive perspective and a basis for future implementation of a very large scale biologically plausible model of thalamo-cortico-thalamic interactivity---the essential brain circuit that regulates the biological sleep-wake cycle and associated EEG rhythms.

  14. Thalamic mediodorsal nucleus and its participation in spatial working memory processes: comparison with the prefrontal cortex

    Science.gov (United States)

    Funahashi, Shintaro

    2013-01-01

    Working memory is a dynamic neural system that includes processes for temporarily maintaining and processing information. Working memory plays a significant role in a variety of cognitive functions, such as thinking, reasoning, decision-making, and language comprehension. Although the prefrontal cortex (PFC) is known to play an important role in working memory, several lines of evidence indicate that the thalamic mediodorsal nucleus (MD) also participates in this process. While monkeys perform spatial working memory tasks, MD neurons exhibit directionally selective delay-period activity, which is considered to be a neural correlate for the temporary maintenance of information in PFC neurons. Studies have also shown that, while most MD neurons maintain prospective motor information, some maintain retrospective sensory information. Thus, the MD plays a greater role in prospective motor aspects of working memory processes than the PFC, which participates more in retrospective aspects. For the performance of spatial working memory tasks, the information provided by a sensory cue needs to be transformed into motor information to give an appropriate response. A population vector analysis using neural activities revealed that, although the transformation of sensory-to-motor information occurred during the delay period in both the PFC and the MD, PFC activities maintained sensory information until the late phase of the delay period, while MD activities initially represented sensory information but then started to represent motor information in the earlier phase of the delay period. These results indicate that long-range neural interactions supported by reciprocal connections between the MD and the PFC could play an important role in the transformation of maintained information in working memory processes. PMID:23914160

  15. Transient Relay Function of Midline Thalamic Nuclei during Long-Term Memory Consolidation in Humans

    Science.gov (United States)

    Thielen, Jan-Willem; Takashima, Atsuko; Rutters, Femke; Tendolkar, Indira; Fernández, Guillén

    2015-01-01

    To test the hypothesis that thalamic midline nuclei play a transient role in memory consolidation, we reanalyzed a prospective functional MRI study, contrasting recent and progressively more remote memory retrieval. We revealed a transient thalamic connectivity increase with the hippocampus, the medial prefrontal cortex (mPFC), and a…

  16. Clinical analysis of electrolyte imbalance in thalamic hemorrhage patients within 24 h after admission.

    Science.gov (United States)

    Guo, Zhenwei; Wang, Tianzhu; Zhang, John H; Qin, Xinyue

    2011-01-01

    We have observed that patients with thalamic hemorrhage are more likely to have electrolyte disturbances than those with non-thalamic hemorrhage. Here, we are attempting to provide some comprehensive information on electrolyte disturbances in patients with thalamic hemorrhage. Retrospectively, 67 patients with thalamic hemorrhage (TH group) and 256 with non-thalamic hemorrhage (N-TH group) were found from computer tomography images. Electrolytes of these patients were tested within 24 h after hospitalization. Chi-square test was used to compare the incidence of electrolyte imbalance. Serum K+ levels were found to be abnormal in 37.31% of the patients in the TH group and 24.21% in the N-TH group, and the difference was significant (pelectrolyte disturbances (42.50%) was higher than that of patients with normal electrolyte levels (14.81%, pelectrolyte imbalance is higher in patients with thalamic hemorrhage than in those with non-thalamic hemorrhage. The reason may be partly related to the location of the hemorrhage. Electrolyte disturbance may contribute to the higher mortality of patients with thalamic hemorrhage.

  17. Multicentre European study of thalamic stimulation in parkinsonian and essential tremor

    NARCIS (Netherlands)

    Limousin, P.; Speelman, J. D.; Gielen, F.; Janssens, M.

    1999-01-01

    Thalamic stimulation has been proposed to treat disabling tremor. The aims of this multicentre study were to evaluate the efficacy and the morbidity of thalamic stimulation in a large number of patients with parkinsonian or essential tremor. One hundred and eleven patients were included in the study

  18. Action of ethanol on responses to nicotine from cerebellar Purkinje neurons: relationship to methyllycaconitine (MLA) inhibition of nicotine responses.

    Science.gov (United States)

    Yang, X; Criswell, H E; Breese, G R

    1999-08-01

    The effect of ethanol on responses to nicotine from rat cerebellar Purkinje neurons was investigated using extracellular single-unit recording. Systemic administration of ethanol initially enhanced the nicotine-induced inhibition from 50% of the Purkinje neurons. However, irrespective of whether there was an initial enhancement, systemic administration of ethanol antagonized the response to nicotine from the majority of Purkinje neurons. When varying ethanol concentrations were electro-osmotically applied to this neuronal cell type, the responses to nicotine (6/8) were enhanced when a low concentration of ethanol (40 mM) was in the pipette, whereas the majority of nicotine responses (10/11) were antagonized when a higher concentration of ethanol (160 mM) was applied to Purkinje neurons. Thus, the concentration of ethanol presented to the neuron seemed to explain the biphasic consequence of systemically administered ethanol on responses to nicotine. In order to determine whether ethanol affected a specific nACh receptor subtype containing the alpha-7 subunit, it was initially established that the nicotinic antagonists, alpha-bungarotoxin (alpha-BTX) and methyllycaconitine (MLA), which are associated with this subunit, had identical actions on responses to nicotine from Purkinje neurons. When MLA was tested against responses to nicotine from this cell type, MLA antagonized the response to nicotine from 45% (9/20) of the neurons tested. In a direct comparison of the action of ethanol to inhibit responses to nicotine with the action of MLA on the same Purkinje neuron, ethanol inhibited responses to nicotine on all neurons sensitive to MLA. However, ethanol also affected nicotine-induced neural changes from some Purkinje neurons not sensitive to MLA antagonism of nicotine. These data support the supposition that ethanol affects a nACh receptor subtype which has an alpha-7 subunit as well as other nACh receptor subtypes without this specific subunit.

  19. Phase dependent modulation of tremor amplitude in essential tremor through thalamic stimulation

    Science.gov (United States)

    Cagnan, Hayriye; Brittain, John-Stuart; Little, Simon; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Hariz, Marwan; Joint, Carole; Fitzgerald, James; Green, Alexander L.; Aziz, Tipu

    2013-01-01

    High frequency deep brain stimulation of the thalamus can help ameliorate severe essential tremor. Here we explore how the efficacy, efficiency and selectivity of thalamic deep brain stimulation might be improved in this condition. We started from the hypothesis that the effects of electrical stimulation on essential tremor may be phase dependent, and that, in particular, there are tremor phases at which stimuli preferentially lead to a reduction in the amplitude of tremor. The latter could be exploited to improve deep brain stimulation, particularly if tremor suppression could be reinforced by cumulative effects. Accordingly, we stimulated 10 patients with essential tremor and thalamic electrodes, while recording tremor amplitude and phase. Stimulation near the postural tremor frequency entrained tremor. Tremor amplitude was also modulated depending on the phase at which stimulation pulses were delivered in the tremor cycle. Stimuli in one half of the tremor cycle reduced median tremor amplitude by ∼10%, while those in the opposite half of the tremor cycle increased tremor amplitude by a similar amount. At optimal phase alignment tremor suppression reached 27%. Moreover, tremor amplitude showed a non-linear increase in the degree of suppression with successive stimuli; tremor suppression was increased threefold if a stimulus was preceded by four stimuli with a similar phase relationship with respect to the tremor, suggesting cumulative, possibly plastic, effects. The present results pave the way for a stimulation system that tracks tremor phase to control when deep brain stimulation pulses are delivered to treat essential tremor. This would allow treatment effects to be maximized by focussing stimulation on the optimal phase for suppression and by ensuring that this is repeated over many cycles so as to harness cumulative effects. Such a system might potentially achieve tremor control with far less power demand and greater specificity than current high frequency

  20. The Strain-Encoded Relationship between PrPSc Replication, Stability and Processing in Neurons is Predictive of the Incubation Period of Disease

    Science.gov (United States)

    Ayers, Jacob I.; Schutt, Charles R.; Shikiya, Ronald A.; Aguzzi, Adriano; Kincaid, Anthony E.; Bartz, Jason C.

    2011-01-01

    Prion strains are characterized by differences in the outcome of disease, most notably incubation period and neuropathological features. While it is established that the disease specific isoform of the prion protein, PrPSc, is an essential component of the infectious agent, the strain-specific relationship between PrPSc properties and the biological features of the resulting disease is not clear. To investigate this relationship, we examined the amplification efficiency and conformational stability of PrPSc from eight hamster-adapted prion strains and compared it to the resulting incubation period of disease and processing of PrPSc in neurons and glia. We found that short incubation period strains were characterized by more efficient PrPSc amplification and higher PrPSc conformational stabilities compared to long incubation period strains. In the CNS, the short incubation period strains were characterized by the accumulation of N-terminally truncated PrPSc in the soma of neurons, astrocytes and microglia in contrast to long incubation period strains where PrPSc did not accumulate to detectable levels in the soma of neurons but was detected in glia similar to short incubation period strains. These results are inconsistent with the hypothesis that a decrease in conformational stability results in a corresponding increase in replication efficiency and suggest that glia mediated neurodegeneration results in longer survival times compared to direct replication of PrPSc in neurons. PMID:21437239

  1. Quantitative relationships between huntingtin levels, polyglutamine length, inclusion body formation, and neuronal death provide novel insight into Huntington’s disease molecular pathogenesis

    Science.gov (United States)

    Miller, Jason; Arrasate, Montserrat; Shaby, Benjamin A.; Mitra, Siddhartha; Masliah, Eliezer; Finkbeiner, Steven

    2010-01-01

    An expanded polyglutamine (polyQ) stretch in the protein huntingtin (htt) induces self-aggregation into inclusion bodies (IBs) and causes Huntington’s disease (HD). Defining precise relationships between early observable variables and neuronal death at the molecular and cellular levels should improve our understanding of HD pathogenesis. Here, we utilized an automated microscope that can track thousands of neurons individually over their entire lifetime to quantify interconnected relationships between early variables, such as htt levels, polyQ length, and IB formation, and neuronal death in a primary striatal model of HD. The resulting model revealed that: mutant htt increases the risk of death by tonically interfering with homeostatic coping mechanisms rather than producing accumulated damage to the neuron; htt toxicity is saturable; the rate limiting steps for inclusion body formation and death can be traced to different conformational changes in monomeric htt; and IB formation reduces the impact of a neuron’s starting levels of htt on its risk of death. Finally, the model that emerges from our quantitative measurements places critical limits on the potential mechanisms by which mutant htt might induce neurodegeneration, which should help direct future research. PMID:20685997

  2. The slow oscillation in cortical and thalamic networks: mechanisms and functions

    Directory of Open Access Journals (Sweden)

    Garrett T. Neske

    2016-01-01

    Full Text Available During even the most quiescent behavioral periods, the cortex and thalamus express rich spontaneous activity in the form of slow (<1 Hz, synchronous network state transitions. Throughout this so-called slow oscillation, cortical and thalamic neurons fluctuate between periods of intense synaptic activity (Up states and almost complete silence (Down states. The two decades since the original characterization of the slow oscillation in the cortex and thalamus have seen considerable advances in deciphering the cellular and network mechanisms associated with this pervasive phenomenon. There are, nevertheless, many questions regarding the slow oscillation that await more thorough illumination, particularly the mechanisms by which Up states initiate and terminate, the functional role of the rhythmic activity cycles in unconscious or minimally conscious states, and the precise relation between Up states and the activated states associated with waking behavior. Given the substantial advances in multineuronal recording and imaging methods in both in vivo and in vitro preparations, the time is ripe to take stock of our current understanding of the slow oscillation and pave the way for future investigations of its mechanisms and functions. My aim in this Review is to provide a comprehensive account of the mechanisms and functions of the slow oscillation, and to suggest avenues for further exploration.

  3. Impact of Neuronal Membrane Damage on the Local Field Potential in a Large-Scale Simulation of Cerebral Cortex

    Directory of Open Access Journals (Sweden)

    David L. Boothe

    2017-06-01

    Full Text Available Within multiscale brain dynamics, the structure–function relationship between cellular changes at a lower scale and coordinated oscillations at a higher scale is not well understood. This relationship may be particularly relevant for understanding functional impairments after a mild traumatic brain injury (mTBI when current neuroimaging methods do not reveal morphological changes to the brain common in moderate to severe TBI such as diffuse axonal injury or gray matter lesions. Here, we created a physiology-based model of cerebral cortex using a publicly released modeling framework (GEneral NEural SImulation System to explore the possibility that performance deficits characteristic of blast-induced mTBI may reflect dysfunctional, local network activity influenced by microscale neuronal damage at the cellular level. We operationalized microscale damage to neurons as the formation of pores on the neuronal membrane based on research using blast paradigms, and in our model, pores were simulated by a change in membrane conductance. We then tracked changes in simulated electrical activity. Our model contained 585 simulated neurons, comprised of 14 types of cortical and thalamic neurons each with its own compartmental morphology and electrophysiological properties. Comparing the functional activity of neurons before and after simulated damage, we found that simulated pores in the membrane reduced both action potential generation and local field potential (LFP power in the 1–40 Hz range of the power spectrum. Furthermore, the location of damage modulated the strength of these effects: pore formation on simulated axons reduced LFP power more strongly than did pore formation on the soma and the dendrites. These results indicate that even small amounts of cellular damage can negatively impact functional activity of larger scale oscillations, and our findings suggest that multiscale modeling provides a promising avenue to elucidate these relationships.

  4. Impact of Neuronal Membrane Damage on the Local Field Potential in a Large-Scale Simulation of Cerebral Cortex.

    Science.gov (United States)

    Boothe, David L; Yu, Alfred B; Kudela, Pawel; Anderson, William S; Vettel, Jean M; Franaszczuk, Piotr J

    2017-01-01

    Within multiscale brain dynamics, the structure-function relationship between cellular changes at a lower scale and coordinated oscillations at a higher scale is not well understood. This relationship may be particularly relevant for understanding functional impairments after a mild traumatic brain injury (mTBI) when current neuroimaging methods do not reveal morphological changes to the brain common in moderate to severe TBI such as diffuse axonal injury or gray matter lesions. Here, we created a physiology-based model of cerebral cortex using a publicly released modeling framework (GEneral NEural SImulation System) to explore the possibility that performance deficits characteristic of blast-induced mTBI may reflect dysfunctional, local network activity influenced by microscale neuronal damage at the cellular level. We operationalized microscale damage to neurons as the formation of pores on the neuronal membrane based on research using blast paradigms, and in our model, pores were simulated by a change in membrane conductance. We then tracked changes in simulated electrical activity. Our model contained 585 simulated neurons, comprised of 14 types of cortical and thalamic neurons each with its own compartmental morphology and electrophysiological properties. Comparing the functional activity of neurons before and after simulated damage, we found that simulated pores in the membrane reduced both action potential generation and local field potential (LFP) power in the 1-40 Hz range of the power spectrum. Furthermore, the location of damage modulated the strength of these effects: pore formation on simulated axons reduced LFP power more strongly than did pore formation on the soma and the dendrites. These results indicate that even small amounts of cellular damage can negatively impact functional activity of larger scale oscillations, and our findings suggest that multiscale modeling provides a promising avenue to elucidate these relationships.

  5. Thalamic, brainstem, and cerebellar glucose metabolism in the hemiplegic monkey

    Energy Technology Data Exchange (ETDEWEB)

    Shimoyama, I.; Dauth, G.W.; Gilman, S.; Frey, K.A.; Penney, J.B. Jr.

    1988-12-01

    Unilateral ablation of cerebral cortical areas 4 and 6 of Brodmann in the macaque monkey results in a contralateral hemiplegia that resolves partially with time. During the phase of dense hemiplegia, local cerebral metabolic rate for glucose (1CMRG1c) is decreased significantly in most of the thalamic nuclei ipsilateral to the ablation, and there are slight contralateral decreases. The lCMRGlc is reduced bilaterally in most of the brainstem nuclei and bilaterally in the deep cerebellar nuclei, but only in the contralateral cerebellar cortex. During the phase of partial motor recovery, lCMRGlc is incompletely restored in many of the thalamic nuclei ipsilateral to the ablation and completely restored in the contralateral nuclei. In the brainstem and deep cerebellar nuclei, poor to moderate recovery occurs bilaterally. Moderate recovery occurs in the contralateral cerebellar cortex. The findings demonstrate that a unilateral cerebral cortical lesion strongly affects lCMRGlc in the thalamus ipsilaterally and in the cerebellar cortex contralaterally, but in the brainstem bilaterally. Partial recovery of lCMRGlc accompanies the progressive motor recovery. The structures affected include those with direct, and also those with indirect, connections to the areas ablated.

  6. Isolated thalamic agraphia with impaired grapheme formation and micrographia.

    Science.gov (United States)

    Sakurai, Yasuhisa; Yoshida, Yukinaga; Sato, Koki; Sugimoto, Izumi; Mannen, Toru

    2011-08-01

    Two patients with isolated thalamic agraphia are described. Both showed kanji (Japanese morphograms) agraphia due to impaired character recall, grapheme deformity and micrographia (progressive reduction in character size during writing) after a lesion that involved the ventral lateral and ventroposterolateral nuclei. Single photon emission computed tomography with a (99m)Tc-ethylcysteinate dimer revealed hypoperfusion in the left precentral gyrus (Brodmann Area 6) and anterior supramarginal gyrus in both. Six months later, the extent of blood flow reduction decreased in the supramarginal gyrus in both patients and the precentral gyrus in patient 1. By this time, the writing impairment improved to nearly the normal range. Our study suggests that kanji agraphia (corresponding to lexical agraphia in Western countries) with poor grapheme formation and micrographia arises from a lesion in the ventral lateral and ventroposterolateral nuclei in the left thalamus. The accompaniment of poor grapheme formation and micrographia may reflect disruption of the cortico-subcortical motor circuit involving the putamen, thalamus, premotor cortex and sensorimotor cortex. It is also suggested that multiple cortical sites can be a target for secondary dysfunction that yields agraphia in a thalamic lesion, and that the recovery of reduced cortical blood flow does not always proceed in parallel with that of agraphia.

  7. Thalamocortical projections of the anteroventral thalamic nucleus in the rabbit.

    Science.gov (United States)

    Shibata, Hideshi; Yoshiko, Honda

    2015-04-01

    The anterior thalamic nuclei are one of the regions that play critical roles in behavioral learning and memory functions. A part of the anterior thalamic nuclei, the anteroventral nucleus (AV) is well developed and differentiated into the parvocellular (AVp) and magnocellular (AVm) division in the rabbit. The AV is crucial for learning discriminative avoidance conditioning. Although communication between the AV and cortex is considered important in learning, little is known about the neural connections of the AV in the rabbit. Thus, this study used anterograde tracer biotinylated dextran amine and the retrograde tracer cholera toxin B subunit to examine the organization of the thalamocortical projections of the AV. Our data show that each division of the AV provides a unique set of projections to restricted regions and layers of the retrosplenial cortex and presubiculum. In addition, the AVp projects to layers I and IV of retrosplenial areas 29 and 30 and to layers I and VI of the presubiculum. The dorsolateral AVm projects to layers I and IV of area 29 and to layers I, III, and V of the presubiculum. However, the ventromedial AVm only projects to layer I of area 29. These projections are generally organized such that the rostral-to-caudal axis of the AV corresponds to the caudal-to-rostral axis of the retrosplenial cortex and to the temporal-to-septal axis of the presubiculum. These findings suggest distinct functional roles played by each division of the AV in the learning and memory functions. © 2014 Wiley Periodicals, Inc.

  8. Network dynamics in nociceptive pathways assessed by the neuronal avalanche model

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    Wu José

    2012-04-01

    Full Text Available Abstract Background Traditional electroencephalography provides a critical assessment of pain responses. The perception of pain, however, may involve a series of signal transmission pathways in higher cortical function. Recent studies have shown that a mathematical method, the neuronal avalanche model, may be applied to evaluate higher-order network dynamics. The neuronal avalanche is a cascade of neuronal activity, the size distribution of which can be approximated by a power law relationship manifested by the slope of a straight line (i.e., the α value. We investigated whether the neuronal avalanche could be a useful index for nociceptive assessment. Findings Neuronal activity was recorded with a 4 × 8 multichannel electrode array in the primary somatosensory cortex (S1 and anterior cingulate cortex (ACC. Under light anesthesia, peripheral pinch stimulation increased the slope of the α value in both the ACC and S1, whereas brush stimulation increased the α value only in the S1. The increase in α values was blocked in both regions under deep anesthesia. The increase in α values in the ACC induced by peripheral pinch stimulation was blocked by medial thalamic lesion, but the increase in α values in the S1 induced by brush and pinch stimulation was not affected. Conclusions The neuronal avalanche model shows a critical state in the cortical network for noxious-related signal processing. The α value may provide an index of brain network activity that distinguishes the responses to somatic stimuli from the control state. These network dynamics may be valuable for the evaluation of acute nociceptive processes and may be applied to chronic pathological pain conditions.

  9. Fluorescent tube light evokes flicker responses in visual neurons.

    Science.gov (United States)

    Eysel, U T; Burandt, U

    1984-01-01

    Single neurons in the cat visual system respond distinctly to the temporal information present in light from fluorescent tubes driven by 50 or 60 Hz alternating current. Despite the resulting flicker frequencies of 100 or 120 Hz all retinal and most thalamic neurons show strong phase locking of the neuronal responses to the modulation of fluorescent tube light. Some retinal ganglion cells have not yet reached their critical flicker fusion frequency under such conditions. Though usually beyond perception, the frequency and depth of modulation of artificial light thus might well play a role in biological light effects.

  10. Anatomical Variations in the Posterior Circle of Willis and Vascular Pathologies in Isolated Unilateral Thalamic Infarction.

    Science.gov (United States)

    Goerlitz, Johannes; Wenz, Holger; Al-Zghloul, Mansour; Kerl, Hans U; Groden, Christoph; Förster, Alex

    2015-01-01

    To characterize relations between configurations of the posterior part of the Circle of Willis (CoW) and the occurrence of unilateral thalamic infarction. From a magnetic resonance imaging report database, we identified and analyzed 111 patients with acute isolated unilateral thalamic infarction on diffusion-weighted imaging (DWI). Vascular pathologies were noted on magnetic resonance angiography (MRA) and the diameter of the posterior communicating artery (PComA) and the P1 and P2 segments of the posterior cerebral artery determined. Most infarctions were observed in the territory of the inferolateral arteries (70.2%), followed by the paramedian (16.3%), tuberothalamic (8.7%), and posterior choroidal arteries (4.8%). Relevant vascular pathologies included stenosis of the basilar artery (4.5%), P1 segment stenosis (4.5%)/occlusion (.9%), and P2 segment stenosis (14.4%)/occlusion (4.5%). Paramedian thalamic infarction was associated with ipsilateral P1 segment hypoplasia/absence (P < .001); tuberothalamic infarction with ipsilateral PComA hypoplasia/absence (P = .08). Furthermore, the diameter of the relevant CoW segment was smaller in patients with ipsilateral thalamic infarction. Assessment of CoW configuration on MRA may be helpful to understand the appearance of unilateral thalamic stroke independent from stroke etiology. A smaller diameter of the relevant CoW segment might be a risk factor for ipsilateral thalamic stroke in the corresponding thalamic vascular territory. Copyright © 2015 by the American Society of Neuroimaging.

  11. Unified thalamic model generates multiple distinct oscillations with state-dependent entrainment by stimulation.

    Science.gov (United States)

    Li, Guoshi; Henriquez, Craig S; Fröhlich, Flavio

    2017-10-01

    The thalamus plays a critical role in the genesis of thalamocortical oscillations, yet the underlying mechanisms remain elusive. To understand whether the isolated thalamus can generate multiple distinct oscillations, we developed a biophysical thalamic model to test the hypothesis that generation of and transition between distinct thalamic oscillations can be explained as a function of neuromodulation by acetylcholine (ACh) and norepinephrine (NE) and afferent synaptic excitation. Indeed, the model exhibited four distinct thalamic rhythms (delta, sleep spindle, alpha and gamma oscillations) that span the physiological states corresponding to different arousal levels from deep sleep to focused attention. Our simulation results indicate that generation of these distinct thalamic oscillations is a result of both intrinsic oscillatory cellular properties and specific network connectivity patterns. We then systematically varied the ACh/NE and input levels to generate a complete map of the different oscillatory states and their transitions. Lastly, we applied periodic stimulation to the thalamic network and found that entrainment of thalamic oscillations is highly state-dependent. Our results support the hypothesis that ACh/NE modulation and afferent excitation define thalamic oscillatory states and their response to brain stimulation. Our model proposes a broader and more central role of the thalamus in the genesis of multiple distinct thalamo-cortical rhythms than previously assumed.

  12. Effects of donepezil on behavioural manifestations of thalamic infarction: a single case observation

    Directory of Open Access Journals (Sweden)

    Rodrigo eRiveros

    2011-03-01

    Full Text Available Objective: To examine the effect of donepezil for the treatment of cognitive and behavioural disorders associated with thalamic lesions in a 45 years old male who suffered an infarct in the left thalamus. Background: Recent studies suggest that donepezil may improve executive functions impairments due to subcortical ischemic lesionsMethod: The crossover effects of donepezil were analyzed in a single case of thalamic infarction with cognitive and behavioural alterations. Results: Significant behavioural modifications related to improved performances in executive functions were observed with the treatment. Conclusions: The results suggest that donepezil may have significant effect on executive functions that can alter behavioural outcomes after thalamic infarctions

  13. Severe personality changes after unilateral left paramedian thalamic infarct.

    Science.gov (United States)

    Fukutake, Toshio; Akada, Koichi; Ito, Shoichi; Okuda, Tomoko; Ueki, Yoshihiro

    2002-01-01

    Personality changes are not uncommon after paramedian thalamic infarction, but usually bilateral or relatively large lesions, often complicated by other neurological or neuropsychological deficits, are present. 'Pure' cases of unilateral lesions are extremely rare. We report that a right-handed, 48-year-old man, who was hypertensive and diabetic but had no prior psychiatric history, developed severe personality changes and a frontal-like syndrome after recovery from acute-onset impairment of consciousness at the age of 43. Other neurological and neuropsychological disturbances, especially verbal and visual amnesia, were unremarkable. MRI showed a very small infarct in the left paramedian area of the thalamus, mainly involving the dorsomedial nucleus. Copyright 2002 S. Karger AG, Basel

  14. Thalamic Ventral Intermediate Nucleus Deep Brain Stimulation for Orthostatic Tremor

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    Alexander C. Lehn

    2017-07-01

    Full Text Available Background: Orthostatic tremor (OT was first described in 1977. It is characterized by rapid tremor of 13–18 Hz and can be recorded in the lower limbs and trunk muscles. OT remains difficult to treat, although some success has been reported with deep brain stimulation (DBS.Case Report: We report a 68-year-old male with OT who did not improve significantly after bilateral thalamic stimulation.Discussion: Although some patients were described who improved after DBS surgery, more information is needed about the effect of these treatment modalities on OT, ideally in the form of randomized trial data. 

  15. Serotonin-immunoreactive neurons in the ventral nerve cord of Remipedia (Crustacea): support for a sister group relationship of Remipedia and Hexapoda?

    Science.gov (United States)

    Stemme, Torben; Iliffe, Thomas M; von Reumont, Björn M; Koenemann, Stefan; Harzsch, Steffen; Bicker, Gerd

    2013-06-10

    Remipedia were initially seen as a primitive taxon within Pancrustacea based on characters considered ancestral, such as the homonomously segmented trunk. Meanwhile, several morphological and molecular studies proposed a more derived position of Remipedia within Pancrustacea, including a sister group relationship to Hexapoda. Because of these conflicting hypotheses, fresh data are crucial to contribute new insights into euarthropod phylogeny. The architecture of individually identifiable serotonin-immunoreactive neurons has successfully been used for phylogenetic considerations in Euarthropoda. Here, we identified neurons in three species of Remipedia with an antiserum against serotonin and compared our findings to reconstructed ground patterns in other euarthropod taxa. Additionally, we traced neurite connectivity and neuropil outlines using antisera against acetylated α-tubulin and synapsin. The ventral nerve cord of Remipedia displays a typical rope-ladder-like arrangement of separate metameric ganglia linked by paired longitudinally projecting connectives. The peripheral projections comprise an intersegmental nerve, consisting of two branches that fuse shortly after exiting the connectives, and the segmental anterior and posterior nerve. The distribution and morphology of serotonin-immunoreactive interneurons in the trunk segments is highly conserved within the remipede species we analyzed, which allows for the reconstruction of a ground pattern: two posterior and one anterior pair of serotonin-immunoreactive neurons that possess a single contralateral projection. Additionally, three pairs of immunoreactive neurons are found in the medial part of each hemiganglion. In one species (Cryptocorynetes haptodiscus), the anterior pair of immunoreactive neurons is missing. The anatomy of the remipede ventral nerve cord with its separate metameric ganglia mirrors the external morphology of the animal's trunk. The rope-ladder-like structure and principal architecture of

  16. Thalamic Stroke and Associated Behavior Disorders. Possibilities for Integral Management: Case Report

    National Research Council Canada - National Science Library

    Camargo, Loida Camargo; Sánchez, Katherine Parra

    2012-01-01

    .... Case report of a 56-year male patient with thalamic ischemia. The intervention with integral strategies involving pharmacological management and cognitive interventions was decisive for the satisfactory evolution of the patient...

  17. Prenatal thalamic waves regulate cortical area size prior to sensory processing

    Science.gov (United States)

    Moreno-Juan, Verónica; Filipchuk, Anton; Antón-Bolaños, Noelia; Mezzera, Cecilia; Gezelius, Henrik; Andrés, Belen; Rodríguez-Malmierca, Luis; Susín, Rafael; Schaad, Olivier; Iwasato, Takuji; Schüle, Roland; Rutlin, Michael; Nelson, Sacha; Ducret, Sebastien; Valdeolmillos, Miguel; Rijli, Filippo M.; López-Bendito, Guillermina

    2017-01-01

    The cerebral cortex is organized into specialized sensory areas, whose initial territory is determined by intracortical molecular determinants. Yet, sensory cortical area size appears to be fine tuned during development to respond to functional adaptations. Here we demonstrate the existence of a prenatal sub-cortical mechanism that regulates the cortical areas size in mice. This mechanism is mediated by spontaneous thalamic calcium waves that propagate among sensory-modality thalamic nuclei up to the cortex and that provide a means of communication among sensory systems. Wave pattern alterations in one nucleus lead to changes in the pattern of the remaining ones, triggering changes in thalamic gene expression and cortical area size. Thus, silencing calcium waves in the auditory thalamus induces Rorβ upregulation in a neighbouring somatosensory nucleus preluding the enlargement of the barrel-field. These findings reveal that embryonic thalamic calcium waves coordinate cortical sensory area patterning and plasticity prior to sensory information processing. PMID:28155854

  18. Characteristics of thalamic local field potentials in patients with disorders of consciousness.

    Science.gov (United States)

    Huang, Yongzhi; He, Jianghong; Green, Alexander L; Aziz, Tipu Z; Stein, John F; Wang, Shouyan

    2015-08-01

    A functioning thalamus is essential for treatment of patients with disorders of consciousness (DOC) using deep brain stimulation (DBS). This work aims to identify the potential biomarkers related to consciousness from the thalamic deep brain local field potentials (LFPs) in DOC patients. The frequency features of central thalamic LFPs were characterized with spectral analysis. The features were further compared to those of LFPs from the ventroposterior lateral nucleus of the thalamus (VPL) in patients with pain. There are several distinct characteristics of thalamic LFPs found in patients with DOC. The most important feature is the oscillation around 10Hz which could be relevant to the existence of residual consciousness, whereas high power below 8Hz seemed to be associated with loss of consciousness. The invasive deep brain recording tool opens a unique way to explore the brain function in consciousness, awareness and alertness and clarify the potential mechanisms of thalamic stimulation in DOC.

  19. Robust modulation of arousal regulation, performance, and frontostriatal activity through central thalamic deep brain stimulation in healthy nonhuman primates

    Science.gov (United States)

    Ryou, Jae-Wook; Wei, Xuefeng F.; Butson, Christopher R.; Schiff, Nicholas D.; Purpura, Keith P.

    2016-01-01

    The central thalamus (CT) is a key component of the brain-wide network underlying arousal regulation and sensory-motor integration during wakefulness in the mammalian brain. Dysfunction of the CT, typically a result of severe brain injury (SBI), leads to long-lasting impairments in arousal regulation and subsequent deficits in cognition. Central thalamic deep brain stimulation (CT-DBS) is proposed as a therapy to reestablish and maintain arousal regulation to improve cognition in select SBI patients. However, a mechanistic understanding of CT-DBS and an optimal method of implementing this promising therapy are unknown. Here we demonstrate in two healthy nonhuman primates (NHPs), Macaca mulatta, that location-specific CT-DBS improves performance in visuomotor tasks and is associated with physiological effects consistent with enhancement of endogenous arousal. Specifically, CT-DBS within the lateral wing of the central lateral nucleus and the surrounding medial dorsal thalamic tegmental tract (DTTm) produces a rapid and robust modulation of performance and arousal, as measured by neuronal activity in the frontal cortex and striatum. Notably, the most robust and reliable behavioral and physiological responses resulted when we implemented a novel method of CT-DBS that orients and shapes the electric field within the DTTm using spatially separated DBS leads. Collectively, our results demonstrate that selective activation within the DTTm of the CT robustly regulates endogenous arousal and enhances cognitive performance in the intact NHP; these findings provide insights into the mechanism of CT-DBS and further support the development of CT-DBS as a therapy for reestablishing arousal regulation to support cognition in SBI patients. PMID:27582298

  20. Control of Somatosensory Cortical Processing by Thalamic Posterior Medial Nucleus: A New Role of Thalamus in Cortical Function.

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    Carlos Castejon

    Full Text Available Current knowledge of thalamocortical interaction comes mainly from studying lemniscal thalamic systems. Less is known about paralemniscal thalamic nuclei function. In the vibrissae system, the posterior medial nucleus (POm is the corresponding paralemniscal nucleus. POm neurons project to L1 and L5A of the primary somatosensory cortex (S1 in the rat brain. It is known that L1 modifies sensory-evoked responses through control of intracortical excitability suggesting that L1 exerts an influence on whisker responses. Therefore, thalamocortical pathways targeting L1 could modulate cortical firing. Here, using a combination of electrophysiology and pharmacology in vivo, we have sought to determine how POm influences cortical processing. In our experiments, single unit recordings performed in urethane-anesthetized rats showed that POm imposes precise control on the magnitude and duration of supra- and infragranular barrel cortex whisker responses. Our findings demonstrated that L1 inputs from POm imposed a time and intensity dependent regulation on cortical sensory processing. Moreover, we found that blocking L1 GABAergic inhibition or blocking P/Q-type Ca2+ channels in L1 prevents POm adjustment of whisker responses in the barrel cortex. Additionally, we found that POm was also controlling the sensory processing in S2 and this regulation was modulated by corticofugal activity from L5 in S1. Taken together, our data demonstrate the determinant role exerted by the POm in the adjustment of somatosensory cortical processing and in the regulation of cortical processing between S1 and S2. We propose that this adjustment could be a thalamocortical gain regulation mechanism also present in the processing of information between cortical areas.

  1. Oscillatory synchrony between head direction cells recorded bilaterally in the anterodorsal thalamic nuclei.

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    Butler, William N; Taube, Jeffrey S

    2017-05-01

    The head direction (HD) circuit is a complex interconnected network of brain regions ranging from the brain stem to the cortex. Recent work found that HD cells corecorded ipsilaterally in the anterodorsal nucleus (ADN) of the thalamus displayed coordinated firing patterns. A high-frequency oscillation pattern (130-160 Hz) was visible in the cross-correlograms of these HD cell pairs. Spectral analysis further found that the power of this oscillation was greatest at 0 ms and decreased at greater lags, and demonstrated that there was greater synchrony between HD cells with similar preferred firing directions. Here, we demonstrate that the same high-frequency synchrony exists in HD cell pairs recorded contralaterally from one another in the bilateral ADN. When we examined the cross-correlograms of HD cells that were corecorded bilaterally, we observed the same high-frequency (~150- to 200-Hz) oscillatory relationship. The strength of this synchrony was similar to the synchrony seen in ipsilateral HD cell pairs, and the degree of synchrony in each cross-correlogram was dependent on the difference in tuning between the two cells. Additionally, the frequency rate of this oscillation appeared to be independent of the firing rates of the two cross-correlated cells. Taken together, these results imply that the left and right thalamic HD network are functionally related despite an absence of direct anatomical projections. However, anatomical tracing has found that each of the lateral mammillary nuclei (LMN) project bilaterally to both of the ADN, suggesting the LMN may be responsible for the functional connectivity observed between the two ADN. NEW & NOTEWORTHY This study used bilateral recording electrodes to examine whether head direction cells recorded simultaneously in both the left and right thalamus show coordinated firing. Cross-correlations of the cells' spike trains revealed a high-frequency oscillatory pattern similar to that seen in cross-correlations between pairs

  2. Transition dynamics of generalized multiple epileptic seizures associated with thalamic reticular nucleus excitability: A computational study

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    Liu, Suyu; Wang, Qingyun

    2017-11-01

    Presently, we improve a computational framework of thalamocortical circuits related to the Taylor's model to investigate the relationship between thalamic reticular nucleus (RE) excitability and epilepsy. By using bifurcation analysis, we explore the RE's excitability dynamics mechanism in the processes of seizure generation, development and transition. Results show that the seizure-free state, absence seizures, clonic seizures and tonic seizures can be formed as the RE excitability is changed in this established model. Importantly, it is verified that physiological changing GABAA inhibition in RE can elicit absence seizures and clonic seizures and the pathological transitions between these two seizures. Furthermore, when the level of AMPA connection is decreased or increased, this proposed model embraces absence seizures and clonic seizures, and tonic seizures, respectively. Except that, bifurcation mechanisms of dynamical transition of different seizures are analyzed in detail. In addition, hybrid regulations of the reticular nucleus excitability for epileptic seizures are proven to be valid within the suitable levels of AMPA and GABAA connection. Hopefully, the obtained results could be helpful for effective control of epileptic activities with additional pharmacological interference.

  3. Disinhibition of the mediodorsal thalamus induces Fos-like immunoreactivity in both pyramidal and GABA-containing neurons in the medial prefrontal cortex of rats, but does not affect prefrontal extracellular GABA levels

    NARCIS (Netherlands)

    Bubser, M; Brabander, J.M; Timmerman, W; Feenstra, M.G P; Erdtsieck-Ernste, E.B H W; Rinkens, A; van Uum, J.F M; Westerink, B.H.C.

    1998-01-01

    Stimulation of the mediodorsal and midline thalamic nuclei excites cortical neurons and induces c-fos expression in the prefrontal cortex. Data in the literature data suggest that pyramidal neurons are the most likely cellular targets. In order to determine whether cortical interneurons are also

  4. Age at First Exposure to Repetitive Head Impacts Is Associated with Smaller Thalamic Volumes in Former Professional American Football Players.

    Science.gov (United States)

    Schultz, Vivian; Stern, Robert A; Tripodis, Yorghos; Stamm, Julie; Wrobel, Pawel; Lepage, Christian; Weir, Isabelle; Guenette, Jeffrey P; Chua, Alicia; Alosco, Michael L; Baugh, Christine M; Fritts, Nathan G; Martin, Brett M; Chaisson, Christine E; Coleman, Michael J; Lin, Alexander P; Pasternak, Ofer; Shenton, Martha E; Koerte, Inga K

    2017-11-17

    Thalamic atrophy has been associated with exposure to repetitive head impacts (RHI) in professional fighters. The aim of this study is to investigate whether or not age at first exposure (AFE) to RHI is associated with thalamic volume in symptomatic former National Football League (NFL) players at risk for chronic traumatic encephalopathy (CTE). Eighty-six symptomatic former NFL players (mean age = 54.9 ± 7.9 years) were included. T1-weighted data were acquired on a 3T magnetic resonance imager, and thalamic volumes were derived using FreeSurfer. Mood and behavior, psychomotor speed, and visual and verbal memory were assessed. The association between thalamic volume and AFE to playing football and to number of years playing was calculated. Decreased thalamic volume was associated with more years of play (left: p = 0.03; right: p = 0.03). Younger AFE was associated with decreased right thalamic volume (p = 0.014). This association remained significant after adjusting for total years of play. Decreased left thalamic volume was associated with worse visual memory (p = 0.014), whereas increased right thalamic volume was associated with fewer mood and behavior symptoms (p = 0.003). In our sample of symptomatic former NFL players at risk for CTE, total years of play and AFE were associated with decreased thalamic volume. The effect of AFE on right thalamic volume was almost twice as strong as the effect of total years of play. Our findings confirm previous reports of an association between thalamic volume and exposure to RHI. They suggest further that younger AFE may result in smaller thalamic volume later in life.

  5. Reduced thalamic and pontine connectivity in Kleine-Levin syndrome

    Directory of Open Access Journals (Sweden)

    Maria eEngström

    2014-04-01

    Full Text Available The Kleine-Levin syndrome is a rare sleep disorder, characterized by exceptionally long sleep episodes. The neuropathology of the syndrome is unknown and treatment is often inadequate. The aim of the study was to improve understanding of the underlying neuropathology, related to cerebral networks, in Kleine-Levin syndrome during sleep episodes. One patient with Kleine-Levin syndrome and congenital nystagmus, was investigated by resting state functional Magnetic Resonance Imaging during both asymptomatic and hypersomnic periods. Fourteen healthy subjects were also investigated as control samples. Functional connectivity was assessed from seed regions of interest in the thalamus and the dorsal pons. Thalamic connectivity was normal in the asymptomatic patient whereas the connectivity between the brain stem, including dorsal pons, and the thalamus was diminished during hypersomnia. These results suggest that the patient’s nystagmus and hypersomnia might have their pathological origin in adjacent dorsal pontine regions. This finding provides additional knowledge of the cerebral networks involved in the neuropathology of this disabling disorder. Furthermore, these findings regarding a rare syndrome have broad implications and results could be of interest to researchers and clinicians in the whole field of sleep medicine.

  6. The thalamic reticular nucleus: structure, function and concept.

    Science.gov (United States)

    Pinault, Didier

    2004-08-01

    On the basis of theoretical, anatomical, psychological and physiological considerations, Francis Crick (1984) proposed that, during selective attention, the thalamic reticular nucleus (TRN) controls the internal attentional searchlight that simultaneously highlights all the neural circuits called on by the object of attention. In other words, he submitted that during either perception, or the preparation and execution of any cognitive and/or motor task, the TRN sets all the corresponding thalamocortical (TC) circuits in motion. Over the last two decades, behavioural, electrophysiological, anatomical and neurochemical findings have been accumulating, supporting the complex nature of the TRN and raising questions about the validity of this speculative hypothesis. Indeed, our knowledge of the actual functioning of the TRN is still sprinkled with unresolved questions. Therefore, the time has come to join forces and discuss some recent cellular and network findings concerning this diencephalic GABAergic structure, which plays important roles during various states of consciousness. On the whole, the present critical survey emphasizes the TRN's complexity, and provides arguments combining anatomy, physiology and cognitive psychology.

  7. Thalamocortical projections of the anterodorsal thalamic nucleus in the rabbit.

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    Shibata, Hideshi; Honda, Yoshiko

    2012-08-15

    The anterior thalamic nuclei consist of the anterodorsal (AD), anteroventral, and anteromedial nuclei, each of which are highly differentiated and may contribute to different aspects of various cognitive and memory functions. In particular, the AD is unique in that it is implicated in learning at the earliest stage of discriminative avoidance conditioning in the rabbit. To better understand the functional roles played by the AD in memory and learning processes, we analyzed the organization of thalamocortical projections of the AD in the rabbit, using the anterograde tracer biotinylated dextran amine and the retrograde tracer cholera toxin subunit B. The data show that the AD provides strong projections to layers I and IV of area 30 and to layers I, III, IV, and VI of area 29 in the retrosplenial cortex, and to layers I and III-VI of the presubiculum. The projections to the retrosplenial cortex are organized such that the rostral and caudal AD, respectively, project to the caudal and rostral retrosplenial cortex. In contrast, the projections to the presubiculum are not organized topographically. Other minor projections were also observed in the parasubiculum and part of the medial entorhinal area. These results indicate that the AD provides strong projections to the retrosplenial cortex and presubiculum, suggesting that these projections constitute essential pathways to these cortical regions for transmitting mnemonic information, such as a novel conditioning stimulus during the initial stage of avoidance learning. Copyright © 2012 Wiley Periodicals, Inc.

  8. Getting signals into the brain: visual prosthetics through thalamic microstimulation

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    Pezaris, John S.; Eskandar, Emad N.

    2010-01-01

    Common causes of blindness are diseases that affect the ocular structures, such as glaucoma, retinitis pigmentosa, and macular degeneration, rendering the eyes no longer sensitive to light. The visual pathway, however, as a predominantly central structure, is largely spared in these cases. It is thus widely thought that a device-based prosthetic approach to restoration of visual function will be effective and will enjoy similar success as cochlear implants have for restoration of auditory function. In this article the authors review the potential locations for stimulation electrode placement for visual prostheses, assessing the anatomical and functional advantages and disadvantages of each. Of particular interest to the neurosurgical community is placement of deep brain stimulating electrodes in thalamic structures that has shown substantial promise in an animal model. The theory of operation of visual prostheses is discussed, along with a review of the current state of knowledge. Finally, the visual prosthesis is proposed as a model for a general high-fidelity machine-brain interface. PMID:19569894

  9. A case of thalamic syndrome: somatosensory influences on visual orientation

    Science.gov (United States)

    Anastasopoulos, D; Bronstein, A

    1999-01-01

    The ability to set a straight line to the perceived gravitational vertical (subjective visual vertical, SVV) was investigated in a 21 year old woman with long standing left hemihypaesthesia due to a posterior thalamic infarct. The putative structures involved were the somatosensory and vestibular thalamus (VPL, VPM) and associative (pulvinar) thalamus. The SVV was normal when seated upright. When lying on her right side, line settings deviated about 17° to the right, which is the normal A-effect. When lying on the hypaesthetic side the mean SVV remained close to true vertical—that is, the A-effect was absent, and there was a large increase in variability of the SVV settings. The findings support the view that the body tilt-induced bias of the SVV (A-effect) is largely mediated by somatosensory afferents. The finding that the A-effect was absent only when lying on the hypaesthetic side suggests that, during body tilt, the somatosensory system participates in visuogravitational orientation.

 PMID:10449566

  10. Prefrontal-Thalamic Anatomical Connectivity and Executive Cognitive Function in Schizophrenia.

    Science.gov (United States)

    Giraldo-Chica, Monica; Rogers, Baxter P; Damon, Stephen M; Landman, Bennett A; Woodward, Neil D

    2018-03-15

    Executive cognitive functions, including working memory, cognitive flexibility, and inhibition, are impaired in schizophrenia. Executive functions rely on coordinated information processing between the prefrontal cortex (PFC) and thalamus, particularly the mediodorsal nucleus. This raises the possibility that anatomical connectivity between the PFC and mediodorsal thalamus may be 1) reduced in schizophrenia and 2) related to deficits in executive function. The current investigation tested these hypotheses. Forty-five healthy subjects and 62 patients with a schizophrenia spectrum disorder completed a battery of tests of executive function and underwent diffusion-weighted imaging. Probabilistic tractography was used to quantify anatomical connectivity between six cortical regions, including PFC, and the thalamus. Thalamocortical anatomical connectivity was compared between healthy subjects and patients with schizophrenia using region-of-interest and voxelwise approaches, and the association between PFC-thalamic anatomical connectivity and severity of executive function impairment was examined in patients. Anatomical connectivity between the thalamus and PFC was reduced in schizophrenia. Voxelwise analysis localized the reduction to areas of the mediodorsal thalamus connected to lateral PFC. Reduced PFC-thalamic connectivity in schizophrenia correlated with impaired working memory but not cognitive flexibility and inhibition. In contrast to reduced PFC-thalamic connectivity, thalamic connectivity with somatosensory and occipital cortices was increased in schizophrenia. The results are consistent with models implicating disrupted PFC-thalamic connectivity in the pathophysiology of schizophrenia and mechanisms of cognitive impairment. PFC-thalamic anatomical connectivity may be an important target for procognitive interventions. Further work is needed to determine the implications of increased thalamic connectivity with sensory cortex. Copyright © 2017 Society of

  11. Relationship between neuronal network architecture and naming performance in temporal lobe epilepsy: A connectome based approach using machine learning.

    Science.gov (United States)

    Munsell, B C; Wu, G; Fridriksson, J; Thayer, K; Mofrad, N; Desisto, N; Shen, D; Bonilha, L

    2017-09-09

    Impaired confrontation naming is a common symptom of temporal lobe epilepsy (TLE). The neurobiological mechanisms underlying this impairment are poorly understood but may indicate a structural disorganization of broadly distributed neuronal networks that support naming ability. Importantly, naming is frequently impaired in other neurological disorders and by contrasting the neuronal structures supporting naming in TLE with other diseases, it will become possible to elucidate the common systems supporting naming. We aimed to evaluate the neuronal networks that support naming in TLE by using a machine learning algorithm intended to predict naming performance in subjects with medication refractory TLE using only the structural brain connectome reconstructed from diffusion tensor imaging. A connectome-based prediction framework was developed using network properties from anatomically defined brain regions across the entire brain, which were used in a multi-task machine learning algorithm followed by support vector regression. Nodal eigenvector centrality, a measure of regional network integration, predicted approximately 60% of the variance in naming. The nodes with the highest regression weight were bilaterally distributed among perilimbic sub-networks involving mainly the medial and lateral temporal lobe regions. In the context of emerging evidence regarding the role of large structural networks that support language processing, our results suggest intact naming relies on the integration of sub-networks, as opposed to being dependent on isolated brain areas. In the case of TLE, these sub-networks may be disproportionately indicative naming processes that are dependent semantic integration from memory and lexical retrieval, as opposed to multi-modal perception or motor speech production. Copyright © 2017. Published by Elsevier Inc.

  12. Reversible and irreversible knockout of the ventroposterolateral thalamic nucleus measured by intracerebral SEP recordings in the rat brain--an aid to neuronavigation in small nuclei.

    Science.gov (United States)

    Blunk, James A; Burke, Michael; Maarouf, Mohammad; Bührle, Christian P

    2007-05-15

    Centrally active drugs are often hard to administer because of the blood brain barrier, and frequently high systemic doses are required to reach sufficient brain parenchyma concentrations, since these drugs are, additionally, diluted in the total blood volume. Moreover, topical administration via the systemic route is not possible. We here propose a technique for the local, quantitative deposition of active substances at defined intracerebral targets, e.g. the thalamic nuclei. We used a long micropipette and stereotactically advanced it to the desired coordinates under electrophysiological control. The pipette acted as both an electrode for intracerebral recordings and as a transportation means for the drug. The amplitude of intracerebral evoked potentials relayed by the thalamic nucleus to the sensorimotor cortex indicated the distance between the pipette tip and the neurons of the targeted nucleus. Data were obtained from anesthetized rats, where the micropipette was advanced towards the nucleus ventralis posterolateralis (VPL) during contralateral electrical forepaw stimulation and intracerebral recording of somatosensory evoked potentials. Within the VPL we either injected lidocaine or kainic acid, both resulting in an attenuation of the intracerebral as well as the cortical evoked potentials. This proposed tool may be useful for functional investigations of deep brain structures.

  13. Mammalian Brains Are Made of These: A Dataset of the Numbers and Densities of Neuronal and Nonneuronal Cells in the Brain of Glires, Primates, Scandentia, Eulipotyphlans, Afrotherians and Artiodactyls, and Their Relationship with Body Mass.

    Science.gov (United States)

    Herculano-Houzel, Suzana; Catania, Kenneth; Manger, Paul R; Kaas, Jon H

    2015-01-01

    Comparative studies amongst extant species are one of the pillars of evolutionary neurobiology. In the 20th century, most comparative studies remained restricted to analyses of brain structure volume and surface areas, besides estimates of neuronal density largely limited to the cerebral cortex. Over the last 10 years, we have amassed data on the numbers of neurons and other cells that compose the entirety of the brain (subdivided into cerebral cortex, cerebellum, and rest of brain) of 39 mammalian species spread over 6 clades, as well as their densities. Here we provide that entire dataset in a format that is readily useful to researchers of any area of interest in the hope that it will foster the advancement of evolutionary and comparative studies well beyond the scope of neuroscience itself. We also reexamine the relationship between numbers of neurons, neuronal densities and body mass, and find that in the rest of brain, but not in the cerebral cortex or cerebellum, there is a single scaling rule that applies to average neuronal cell size, which increases with the linear dimension of the body, even though there is no single scaling rule that relates the number of neurons in the rest of brain to body mass. Thus, larger bodies do not uniformly come with more neurons--but they do fairly uniformly come with larger neurons in the rest of brain, which contains a number of structures directly connected to sources or targets in the body. © 2015 S. Karger AG, Basel.

  14. Neuronal networks and energy bursts in epilepsy.

    Science.gov (United States)

    Wu, Y; Liu, D; Song, Z

    2015-02-26

    Epilepsy can be defined as the abnormal activities of neurons. The occurrence, propagation and termination of epileptic seizures rely on the networks of neuronal cells that are connected through both synaptic- and non-synaptic interactions. These complicated interactions contain the modified functions of normal neurons and glias as well as the mediation of excitatory and inhibitory mechanisms with feedback homeostasis. Numerous spread patterns are detected in disparate networks of ictal activities. The cortical-thalamic-cortical loop is present during a general spike wave seizure. The thalamic reticular nucleus (nRT) is the major inhibitory input traversing the region, and the dentate gyrus (DG) controls CA3 excitability. The imbalance between γ-aminobutyric acid (GABA)-ergic inhibition and glutamatergic excitation is the main disorder in epilepsy. Adjustable negative feedback that mediates both inhibitory and excitatory components affects neuronal networks through neurotransmission fluctuation, receptor and transmitter signaling, and through concomitant influences on ion concentrations and field effects. Within a limited dynamic range, neurons slowly adapt to input levels and have a high sensitivity to synaptic changes. The stability of the adapting network depends on the ratio of the adaptation rates of both the excitatory and inhibitory populations. Thus, therapeutic strategies with multiple effects on seizures are required for the treatment of epilepsy, and the therapeutic functions on networks are reviewed here. Based on the high-energy burst theory of epileptic activity, we propose a potential antiepileptic therapeutic strategy to transfer the high energy and extra electricity out of the foci. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. Consistent phosphenes generated by electrical microstimulation of the visual thalamus. An experimental approach for thalamic visual neuroprostheses

    Directory of Open Access Journals (Sweden)

    Fivos ePanetsos

    2011-07-01

    Full Text Available Most work on visual prostheses has centred on developing retinal or cortical devices. However, when retinal implants are not feasible, neuroprostheses could be implanted in the lateral geniculate nucleus of the thalamus (LGN, the intermediate relay station of visual information from the retina to the visual cortex (V1. The objective of the present study was to determine the types of artificial stimuli that when delivered to the visual thalamus can generate reliable responses of the cortical neurons similar to those obtained when the eye perceives a visual image. Visual stimuli {Si} were presented to one eye of an experimental animal and both, the thalamic {RThi} and cortical responses {RV1i} to such stimuli were recorded. Electrical patterns {RThi*} resembling {RThi} were then injected into the visual thalamus to obtain cortical responses {RV1i*} similar to {RV1i}. Visually- and electrically-generated V1 responses were compared.Results: During the course of this work we: (i characterised the response of V1 neurons to visual stimuli according to response magnitude, duration, spiking rate and the distribution of interspike intervals; (ii experimentally tested the dependence of V1 responses on stimulation parameters such as intensity, frequency, duration, etc. and determined the ranges of these parameters generating the desired cortical activity; (iii identified similarities between responses of V1 useful to compare the naturally and artificially generated neuronal activity of V1; and (iv by modifying the stimulation parameters, we generated artificial V1 responses similar to those elicited by visual stimuli.Generation of predictable and consistent phosphenes by means of artificial stimulation of the LGN is important for the feasibility of visual prostheses. Here we proved that electrical stimuli to the LGN can generate V1 neural responses that resemble those elicited by natural visual stimuli.

  16. [Thalamic dementia due to infarct of the left thalamus and genum of the right internal capsule].

    Science.gov (United States)

    Porta-Etessam, J; Martínez-Salio, A; Berbel, A; Benito-León, J; García-Muñoz, A; Kesler, P; Mateo, S

    Thalamic dementia is the clinical consequence of a disorder of both thalami. It is generally secondary to bilateral paramedial thalamic infarcts due to disorders of small blood vessels or cardioembolism. We report a case of dementia of acute onset involving the left thalamus and the genum of the right internal capsule. A 33 year old man, HIV positive, category B2, admitted to hospital for tuberculous meningitis presented with the acute onset of somnolence, followed by marked bradypsychism, personality changes, marked disorder of executive explicit memory without associated praxic, gnosic or language disorders. Ocular motility remained normal. There was left central facial paralysis with inverse emotive voluntary dissociation. The other cranial nerves were normal. There was left hemiparesia with extensor plantar reflex. No other alterations. Cerebral MR imaging was compatible with paramedial infarcts of the left thalamus and genum of the right internal capsule. Thalamic dementia generally occurs in bilateral paramedian thalamic disorders. There are cases of disorders of executive memory secondary to infarcts of the genum of the internal capsule due to interruption of the thalamotemporal pathways and a contralateral paramedial thalamic lesion.

  17. Altered resting-state functional connectivity of striatal-thalamic circuit in bipolar disorder.

    Directory of Open Access Journals (Sweden)

    Shin Teng

    Full Text Available Bipolar disorder is characterized by internally affective fluctuations. The abnormality of inherently mental state can be assessed using resting-state fMRI data without producing task-induced biases. In this study, we hypothesized that the resting-state connectivity related to the frontal, striatal, and thalamic regions, which were associated with mood regulations and cognitive functions, can be altered for bipolar disorder. We used the Pearson's correlation coefficients to estimate functional connectivity followed by the hierarchical modular analysis to categorize the resting-state functional regions of interest (ROIs. The selected functional connectivities associated with the striatal-thalamic circuit and default mode network (DMN were compared between bipolar patients and healthy controls. Significantly decreased connectivity in the striatal-thalamic circuit and between the striatal regions and the middle and posterior cingulate cortex was observed in the bipolar patients. We also observed that the bipolar patients exhibited significantly increased connectivity between the thalamic regions and the parahippocampus. No significant changes of connectivity related to the frontal regions in the DMN were observed. The changed resting-state connectivity related to the striatal-thalamic circuit might be an inherent basis for the altered emotional and cognitive processing in the bipolar patients.

  18. Differential impact of thalamic versus subthalamic deep brain stimulation on lexical processing.

    Science.gov (United States)

    Krugel, Lea K; Ehlen, Felicitas; Tiedt, Hannes O; Kühn, Andrea A; Klostermann, Fabian

    2014-10-01

    Roles of subcortical structures in language processing are vague, but, interestingly, basal ganglia and thalamic Deep Brain Stimulation can go along with reduced lexical capacities. To deepen the understanding of this impact, we assessed word processing as a function of thalamic versus subthalamic Deep Brain Stimulation. Ten essential tremor patients treated with thalamic and 14 Parkinson׳s disease patients with subthalamic Deep Brain Stimulation performed an acoustic Lexical Decision Task ON and OFF stimulation. Combined analysis of task performance and event-related potentials allowed the determination of processing speed, priming effects, and N400 as neurophysiological correlate of lexical stimulus processing. 12 age-matched healthy participants acted as control subjects. Thalamic Deep Brain Stimulation prolonged word decisions and reduced N400 potentials. No comparable ON-OFF effects were present in patients with subthalamic Deep Brain Stimulation. In the latter group of patients with Parkinson' disease, N400 amplitudes were, however, abnormally low, whether under active or inactive Deep Brain Stimulation. In conclusion, performance speed and N400 appear to be influenced by state functions, modulated by thalamic, but not subthalamic Deep Brain Stimulation, compatible with concepts of thalamo-cortical engagement in word processing. Clinically, these findings specify cognitive sequels of Deep Brain Stimulation in a target-specific way. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Structure activity relationship, vibrational spectral investigation and molecular docking analysis of anti-neuronal drug 4-(2-Aminoethyl) morpholine

    Science.gov (United States)

    Edwin, Bismi; Amalanathan, M.; Chadha, Ridhima; Maiti, Nandita; Kapoor, Sudhir; Hubert Joe, I.

    2017-11-01

    Vibrational spectral analysis and quantum chemical computations based on density functional theory have been performed on the anti-neuronal drug 4-(2-aminoethyl) morpholine. The geometry, intermolecular hydrogen bond, and harmonic vibrational frequencies of the title molecule have been investigated with the help of B3LYP method. The calculated molecular geometry has been compared with the experimental data. The various intramolecular interactions have been exposed by natural bond orbital analysis. Analysis of SERS bands in comparison to the normal Raman spectrum indicates the chemisorption of the drug on the silver surface. The analysis of the electron density of HOMO and LUMO gives an idea of the delocalization and low value of energy gap indicates electron transport in the molecule and thereby bioactivity. Effective docking of the drug molecule with 2C6C protein also enhances its bioactive nature.

  20. Accelerated forgetting of contextual details due to focal medio-dorsal thalamic lesion

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    Sicong eTu

    2014-09-01

    Full Text Available Effects of thalamic nuclei damage and related white matter tracts on memory performance are still debated. This is particularly evident for the medio-dorsal thalamus which has been less clear in predicting amnesia than anterior thalamus changes. The current study addresses this issue by assessing 7 thalamic stroke patients with consistent unilateral lesions focal to the left medio-dorsal nuclei for immediate and delayed memory performance on standard visual and verbal tests of anterograde memory, and over the long-term (> 24 hrs on an object-location associative memory task. Thalamic patients showed selective impairment to delayed recall, but intact recognition memory. Patients also showed accelerated forgetting of contextual information after a 24 hour delay, compared to controls. Importantly, the mammillothalamic tract was intact in all patients, which suggests a role for the medio-dorsal nuclei in recall and early consolidation memory processes.

  1. Impairments of thalamic resting-state functional connectivity in patients with chronic tinnitus

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    Zhang, Jian [Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing (China); Chen, Yu-Chen [Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing (China); Center for Hearing and Deafness, University at Buffalo, State University of New York, Buffalo, NY (United States); Feng, Xu [Department of Otolaryngology, Zhongda Hospital, Medical School, Southeast University, Nanjing (China); Yang, Ming; Liu, Bin; Qian, Cheng [Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing (China); Wang, Jian [Department of Physiology, Southeast University, Nanjing (China); School of Human Communication Disorders, Dalhousie University, Halifax, NS (Canada); Salvi, Richard [Center for Hearing and Deafness, University at Buffalo, State University of New York, Buffalo, NY (United States); Teng, Gao-Jun, E-mail: gjteng@vip.sina.com [Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing (China)

    2015-07-15

    Highlights: • Tinnitus patients have aberrant thalamic connectivity to many brain regions. • Decreased thalamic connectivity is linked with tinnitus characteristics. • Thalamocortical connectivity disturbances can reflect tinnitus-related networks. - Abstract: Purpose: The phantom sound of tinnitus is believed to arise from abnormal functional coupling between the thalamus and cerebral cortex. To explore this hypothesis, we used resting-state functional magnetic resonance imaging (fMRI) to compare the degree of thalamocortical functional connectivity in chronic tinnitus patients and controls. Materials and methods: Resting-state fMRI scans were obtained from 31 chronic tinnitus patients and 33 well-matched healthy controls. Thalamocortical functional connectivity was characterized using a seed-based whole-brain correlation method. The resulting thalamic functional connectivity measures were correlated with other clinical data. Results: We found decreased functional connectivity between the seed region in left thalamus and right middle temporal gyrus (MTG), right middle orbitofrontal cortex, left middle frontal gyrus, right precentral gyrus, and bilateral calcarine cortex. Decreased functional connectivity was detected between the seed in the right thalamus and the left superior temporal gyrus (STG), left amygdala, right superior frontal gyrus, left precentral gyrus, and left middle occipital gyrus. Tinnitus distress correlated negatively with thalamic functional connectivity in right MTG; tinnitus duration correlated negatively with thalamic functional connectivity in left STG. Increased functional connectivity between the bilateral thalamus and a set of regions were also observed. Conclusions: Chronic tinnitus patients have disrupted thalamocortical functional connectivity to selected brain regions which is associated with specific tinnitus characteristics. Resting-state thalamic functional connectivity disturbances may play an important role in

  2. Selective importance of the rat anterior thalamic nuclei for configural learning involving distal spatial cues.

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    Dumont, Julie R; Amin, Eman; Aggleton, John P

    2014-01-01

    To test potential parallels between hippocampal and anterior thalamic function, rats with anterior thalamic lesions were trained on a series of biconditional learning tasks. The anterior thalamic lesions did not disrupt learning two biconditional associations in operant chambers where a specific auditory stimulus (tone or click) had a differential outcome depending on whether it was paired with a particular visual context (spot or checkered wall-paper) or a particular thermal context (warm or cool). Likewise, rats with anterior thalamic lesions successfully learnt a biconditional task when they were reinforced for digging in one of two distinct cups (containing either beads or shredded paper), depending on the particular appearance of the local context on which the cup was placed (one of two textured floors). In contrast, the same rats were severely impaired at learning the biconditional rule to select a specific cup when in a particular location within the test room. Place learning was then tested with a series of go/no-go discriminations. Rats with anterior thalamic nuclei lesions could learn to discriminate between two locations when they were approached from a constant direction. They could not, however, use this acquired location information to solve a subsequent spatial biconditional task where those same places dictated the correct choice of digging cup. Anterior thalamic lesions produced a selective, but severe, biconditional learning deficit when the task incorporated distal spatial cues. This deficit mirrors that seen in rats with hippocampal lesions, so extending potential interdependencies between the two sites. © 2013 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  3. Dimensions of the ion channel in neuronal nicotinic acetylcholine receptor as estimated from analysis of conformation-activity relationships of open-channel blocking drugs.

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    Zhorov, B S; Brovtsyna, N B; Gmiro, V E; Lukomskaya NYa; Serdyuk, S E; Potapyeva, N N; Magazanik, L G; Kurenniy, D E; Skok, V I

    1991-04-01

    Relationship between the size of the molecule in the series of organic ions Et3+N--(CH2)5--+NR1R2R3 (Ri--alkyl or cycloalkyl substituents) and their abilities to block nicotinic acetylcholine receptors (AChRs) due to their open-channel blockade in the neurons of autonomic ganglia and in frog end-plate was analyzed. All low-energy equilibrium conformations of the drugs were calculated by the molecular mechanics method. A unique rectangular channel profile 6.1 x 8.3 A, for which the best correlation between blocking activity of the drugs and total population of their conformations being able to penetrate into the channel, was deduced from all those tested.

  4. Multilaminar networks of cortical neurons integrate common inputs from sensory thalamus.

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    Morgenstern, Nicolás A; Bourg, Jacques; Petreanu, Leopoldo

    2016-08-01

    Neurons in the thalamorecipient layers of sensory cortices integrate thalamic and recurrent cortical input. Cortical neurons form fine-scale, functionally cotuned networks, but whether interconnected cortical neurons within a column process common thalamocortical inputs is unknown. We tested how local and thalamocortical connectivity relate to each other by analyzing cofluctuations of evoked responses in cortical neurons after photostimulation of thalamocortical axons. We found that connected pairs of pyramidal neurons in layer (L) 4 of mouse visual cortex share more inputs from the dorsal lateral geniculate nucleus than nonconnected pairs. Vertically aligned connected pairs of L4 and L2/3 neurons were also preferentially contacted by the same thalamocortical axons. Our results provide a circuit mechanism for the observed amplification of sensory responses by L4 circuits. They also show that sensory information is concurrently processed in L4 and L2/3 by columnar networks of interconnected neurons contacted by the same thalamocortical axons.

  5. Lucid dreams, an atypical sleep disturbance in anterior and mediodorsal thalamic strokes.

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    Sagnier, S; Coulon, P; Chaufton, C; Poli, M; Debruxelles, S; Renou, P; Rouanet, F; Olindo, S; Sibon, I

    2015-11-01

    Cognitive, affective, and behavioural disturbances are commonly reported following thalamic strokes. Conversely, sleep disorders are rarely reported in this context. Herein, we report the cases of two young patients admitted for an ischemic stroke located in the territories of the left pre-mammillary and paramedian arteries. Together with aphasia, memory complaint, impaired attention and executive functions, they reported lucid dreams with catastrophic content or conflicting situations. Lucid dreams are an atypical presentation in thalamic strokes. These cases enlarge the clinical spectrum of sleep-wake disturbances potentially observed after an acute cerebrovascular event. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  6. Altered structural connectivity of cortico-striato-pallido-thalamic networks in Gilles de la Tourette syndrome.

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    Worbe, Yulia; Marrakchi-Kacem, Linda; Lecomte, Sophie; Valabregue, Romain; Poupon, Fabrice; Guevara, Pamela; Tucholka, Alan; Mangin, Jean-François; Vidailhet, Marie; Lehericy, Stephane; Hartmann, Andreas; Poupon, Cyril

    2015-02-01

    Gilles de la Tourette syndrome is a childhood-onset syndrome characterized by the presence and persistence of motor and vocal tics. A dysfunction of cortico-striato-pallido-thalamo-cortical networks in this syndrome has been supported by convergent data from neuro-pathological, electrophysiological as well as structural and functional neuroimaging studies. Here, we addressed the question of structural integration of cortico-striato-pallido-thalamo-cortical networks in Gilles de la Tourette syndrome. We specifically tested the hypothesis that deviant brain development in Gilles de la Tourette syndrome could affect structural connectivity within the input and output basal ganglia structures and thalamus. To this aim, we acquired data on 49 adult patients and 28 gender and age-matched control subjects on a 3 T magnetic resonance imaging scanner. We used and further implemented streamline probabilistic tractography algorithms that allowed us to quantify the structural integration of cortico-striato-pallido-thalamo-cortical networks. To further investigate the microstructure of white matter in patients with Gilles de la Tourette syndrome, we also evaluated fractional anisotropy and radial diffusivity in these pathways, which are both sensitive to axonal package and to myelin ensheathment. In patients with Gilles de la Tourette syndrome compared to control subjects, we found white matter abnormalities in neuronal pathways connecting the cerebral cortex, the basal ganglia and the thalamus. Specifically, striatum and thalamus had abnormally enhanced structural connectivity with primary motor and sensory cortices, as well as paracentral lobule, supplementary motor area and parietal cortices. This enhanced connectivity of motor cortex positively correlated with severity of tics measured by the Yale Global Tics Severity Scale and was not influenced by current medication status, age or gender of patients. Independently of the severity of tics, lateral and medial orbito

  7. Role of thalamic projection in NMDA receptor-induced disruption of cortical slow oscillation and short-term plasticity

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    Tamás eKiss

    2011-04-01

    Full Text Available NMDA receptor (NMDAR antagonists, such as phencyclidine, ketamine or dizocilpine (MK-801 are commonly used in psychiatric drug discovery in order to model several symptoms of schizophrenia, including psychosis and impairments in working memory. In spite of the widespread use of NMDAR antagonists in preclinical and clinical studies, our understanding of the mode of action of these drugs on brain circuits and neuronal networks is still limited. In the present study spontaneous local field potential (LFP, multi- (MUA and single unit activity, and evoked potential, including paired-pulse facilitation (PPF in response to electrical stimulation of the ipsilateral subiculum were carried out in the medial prefrontal cortex (mPFC in urethane anesthetized rats. Systemic administration of MK-801 (0.05~mg/kg, i.v. decreased overall MUA, with a diverse effect on single unit activity, including increased, decreased or unchanged firing, and in line with our previous findings shifted delta frequency power of the LFP and disrupted PPF (Kiss et al., Int J Neuropsychopharmacol. 2010. In order to provide further insight to the mechanisms of action of NMDAR antagonists, MK-801 was administered intracranially into the mPFC and mediodorsal nucleus of the thalamus (MD. Microinjections of MK-801, but not physiological saline, localized into the MD evoked changes in both LFP parameters and PPF similar to the effects of systemically administered MK-801. Local microinjection of MK-801 into the mPFC was without effect on these parameters. Our findings indicate that the primary site of the action of systemic administration of NMDA receptor antagonists is unlikely to be the cortex. We presume that multiple neuronal networks, involving thalamic nuclei contribute to disrupted behavior and cognition following NMDA receptor blockade.

  8. Functional disconnection of thalamic and cerebellar dentate nucleus networks in progressive supranuclear palsy and corticobasal syndrome.

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    Upadhyay, Neeraj; Suppa, Antonio; Piattella, Maria Cristina; Giannì, Costanza; Bologna, Matteo; Di Stasio, Flavio; Petsas, Nikolaos; Tona, Francesca; Fabbrini, Giovanni; Berardelli, Alfredo; Pantano, Patrizia

    2017-06-01

    To assess functional rearrangement following neurodegeneration in the thalamus and dentate nucleus in patients with progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). We recruited 19 patients with PSP, 11 with CBS and 14 healthy subjects. All the subjects underwent resting-state (rs) fMRI using a 3T system. Whole brain functional connectivity of the thalamus and dentate nucleus were calculated by means of a seed-based approach with FEAT script in FSL toolbox. Thalamic volume was calculated by means of FIRST, and the dentate area by means of Jim software. Both thalamic volume and dentate area were significantly smaller in PSP and CBS patients than in healthy subjects. No significant difference emerged in thalamic volume between PSP and CBS patients, whereas dentate area was significantly smaller in PSP than in CBS. Thalamic functional connectivity was significantly reduced in both patient groups in various cortical, subcortical and cerebellar areas. By contrast, changes in dentate nucleus functional connectivity differed in PSP and CBS: it decreased in subcortical and prefrontal cortical areas in PSP, but increased asymmetrically in the frontal cortex in CBS. Evaluating the dentate nucleus size and its functional connectivity may help to differentiate patients with PSP from those with CBS. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Complex neurological symptoms in bilateral thalamic stroke due to Percheron artery occlusion

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    Caruso P

    2016-12-01

    Full Text Available Paola Caruso, Paolo Manganotti, Rita Moretti Department of Clinical Neurology, University of Trieste, Trieste, Italy Abstract: The artery of Percheron is a rare anatomical variant where a single thalamic perforating artery arises from the proximal posterior cerebral artery (P1 segment between the basilar artery and the posterior communicating artery and supplies the rostral mesencephalon and both paramedian territories of the thalami. Almost one-third of human brains present this variant. Occlusion of the artery of Percheron mostly results in a bilateral medial thalamic infarction, which usually manifests with altered consciousness (including coma, vertical gaze paresis, and cognitive disturbance. The presentation is similar to the “top of the basilar syndrome”, and early recognition should be prompted. We describe the case of a young female with this vessel variant who experienced a bilateral thalamic stroke. Magnetic resonance angiography demonstrated bilateral thalamic infarcts and a truncated artery of Percheron. Occlusion of the vessel was presumably due to embolism from a patent foramen ovale. Thrombolysis was performed, with incomplete symptom remission, cognitive impairment, and persistence of speech disorders. Early recognition and treatment of posterior circulation strokes is mandatory, and further investigation for underlying stroke etiologies is needed. Keywords: thalamus vascularization, cognitive impairment, paramedian thalamus territory, speech disorder, vertical gaze palsy

  10. Anterior Thalamic Lesions Alter Both Hippocampal-Dependent Behavior and Hippocampal Acetylcholine Release in the Rat

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    Savage, Lisa M.; Hall, Joseph M.; Vetreno, Ryan P.

    2011-01-01

    The anterior thalamic nuclei (ATN) are important for learning and memory as damage to this region produces a persistent amnestic syndrome. Dense connections between the ATN and the hippocampus exist, and importantly, damage to the ATN can impair hippocampal functioning. Acetylcholine (ACh) is a key neurotransmitter in the hippocampus, and in vivo…

  11. Silent diabetes mellitus, periodontitis and a new case of thalamic abscess.

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    Karageorgiou, Ioannis; Chandler, Christopher; Whyte, Martin Brunel

    2014-07-21

    Brain abscess is an unusual complication of uncontrolled diabetes. A solitary thalamic abscess is an uncommon type of brain abscess. We report a case of thalamic abscess, whereupon diabetes mellitus and periodontitis were diagnosed. The diagnosis and management of thalamic abscess, and the interplay of type 2 diabetes and periodontitis are discussed. A 56-year-old, Caucasian, man with no medical or travel history, presented with 5-day symptoms of meningeal irritation. Body mass index 30.6 kg/m(2). CT demonstrated a solitary midline lesion with neoplasia as a differential diagnosis. It was biopsied and cultures grew Streptococcus milleri. He was treated by stereotactic puncture, external drainage and targeted intrathecal and systemic antibiotic therapy. HIV negative but glycated haemoglobin (HbA1c) 10.7% (93 mmol/mol). Dental examination revealed a small molar abscess. Radiological resolution of the thalamic abscess occurred within 2 months. Diabetes improved with 7 weeks of insulin, and maintained on metformin, HbA1c 6.9% (51 mmol/mol). There was no residual neurological disability. 2014 BMJ Publishing Group Ltd.

  12. Long-term follow-up of thalamic stimulation versus thalamotomy for tremor suppression

    NARCIS (Netherlands)

    Schuurman, P. Richard; Bosch, D. Andries; Merkus, Maruschka P.; Speelman, Johannes D.

    2008-01-01

    Thalamic stimulation and thalamotomy for treatment of tremor due to Parkinson's disease, essential tremor, and multiple sclerosis were compared in a randomized trial. The symptomatic and functional outcome was studied after 5 years of follow-up. Sixty-eight patients were treated (45 Parkinson's

  13. Impairment of Syntax and Lexical Semantics in a Patient with Bilateral Paramedian Thalamic Infarction

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    De Witte, Lieve; Wilssens, Ineke; Engelborghs, Sebastian; De Deyn, Peter P.; Marien, Peter

    2006-01-01

    Bilateral vascular thalamic lesions are rare. Although a variety of neurobehavioral manifestations have been described, the literature is less documented with regard to accompanying linguistic disturbances. This article presents an in-depth neurolinguistic analysis of the language symptoms of a patient who incurred bilateral paramedian ischemic…

  14. Neuronal nonlinearity explains greater visual spatial resolution for darks than lights.

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    Kremkow, Jens; Jin, Jianzhong; Komban, Stanley J; Wang, Yushi; Lashgari, Reza; Li, Xiaobing; Jansen, Michael; Zaidi, Qasim; Alonso, Jose-Manuel

    2014-02-25

    Astronomers and physicists noticed centuries ago that visual spatial resolution is higher for dark than light stimuli, but the neuronal mechanisms for this perceptual asymmetry remain unknown. Here we demonstrate that the asymmetry is caused by a neuronal nonlinearity in the early visual pathway. We show that neurons driven by darks (OFF neurons) increase their responses roughly linearly with luminance decrements, independent of the background luminance. However, neurons driven by lights (ON neurons) saturate their responses with small increases in luminance and need bright backgrounds to approach the linearity of OFF neurons. We show that, as a consequence of this difference in linearity, receptive fields are larger in ON than OFF thalamic neurons, and cortical neurons are more strongly driven by darks than lights at low spatial frequencies. This ON/OFF asymmetry in linearity could be demonstrated in the visual cortex of cats, monkeys, and humans and in the cat visual thalamus. Furthermore, in the cat visual thalamus, we show that the neuronal nonlinearity is present at the ON receptive field center of ON-center neurons and ON receptive field surround of OFF-center neurons, suggesting an origin at the level of the photoreceptor. These results demonstrate a fundamental difference in visual processing between ON and OFF channels and reveal a competitive advantage for OFF neurons over ON neurons at low spatial frequencies, which could be important during cortical development when retinal images are blurred by immature optics in infant eyes.

  15. Disrupted thalamic resting-state functional connectivity in patients with minimal hepatic encephalopathy

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    Qi, Rongfeng [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing 210002 (China); Zhang, Long Jiang, E-mail: kevinzhanglongjiang@yahoo.com.cn [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing 210002 (China); Zhong, Jianhui [Department of Biomedical Engineering, Zhejiang University, Hangzhou, Zhejiang 310027 (China); Zhang, Zhiqiang; Ni, Ling; Zheng, Gang [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing 210002 (China); Lu, Guang Ming, E-mail: cjr.luguangming@vip.163.com [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing 210002 (China)

    2013-05-15

    Background and purpose: Little is known about the role of thalamus in the pathophysiology of minimal hepatic encephalopathy (MHE). The purpose of this study was to investigate whether the thalamic functional connectivity was disrupted in cirrhotic patients with MHE by using resting-state functional magnetic resonance imaging (rs-fMRI). Materials and Methods: Twenty seven MHE patients and twenty seven age- and gender- matched healthy controls participated in the rs-fMRI scans. The functional connectivity of 11 thalamic nuclei were characterized by using a standard seed-based whole-brain correlation method and compared between MHE patients and healthy controls. Pearson correlation analysis was performed between the thalamic functional connectivity and venous blood ammonia levels/neuropsychological tests scores of patients. Results: The ventral anterior nucleus (VAN) and the ventral posterior medial nucleus (VPMN) in each side of thalamus showed abnormal functional connectivities in MHE. Compared with healthy controls, MHE patients demonstrated significant decreased functional connectivity between the right/left VAN and the bilateral putamen/pallidum, inferior frontal gyri, insula, supplementary motor area, right middle frontal gyrus, medial frontal gyrus. In addition, MHE patients showed significantly decreased functional connectivity with the right/left VPMN in the bilateral middle temporal gyri (MTG), temporal lobe, and right superior temporal gyrus. The venous blood ammonia levels of MHE patients negatively correlated with the functional connectivity between the VAN and the insula. Number connecting test scores showed negative correlation with the functional connectivity between the VAN and the insula, and between the VPMN and the MTG. Conclusion: MHE patients had disrupted thalamic functional connectivity, which mainly located in the bilateral ventral anterior nuclei and ventral posterior medial nuclei. The decreased connectivity between thalamus and many

  16. Dynamical analysis of Parkinsonian state emulated by hybrid Izhikevich neuron models

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    Liu, Chen; Wang, Jiang; Yu, Haitao; Deng, Bin; Wei, Xile; Li, Huiyan; Loparo, Kenneth A.; Fietkiewicz, Chris

    2015-11-01

    Computational models play a significant role in exploring novel theories to complement the findings of physiological experiments. Various computational models have been developed to reveal the mechanisms underlying brain functions. Particularly, in the development of therapies to modulate behavioral and pathological abnormalities, computational models provide the basic foundations to exhibit transitions between physiological and pathological conditions. Considering the significant roles of the intrinsic properties of the globus pallidus and the coupling connections between neurons in determining the firing patterns and the dynamical activities of the basal ganglia neuronal network, we propose a hypothesis that pathological behaviors under the Parkinsonian state may originate from combined effects of intrinsic properties of globus pallidus neurons and synaptic conductances in the whole neuronal network. In order to establish a computational efficient network model, hybrid Izhikevich neuron model is used due to its capacity of capturing the dynamical characteristics of the biological neuronal activities. Detailed analysis of the individual Izhikevich neuron model can assist in understanding the roles of model parameters, which then facilitates the establishment of the basal ganglia-thalamic network model, and contributes to a further exploration of the underlying mechanisms of the Parkinsonian state. Simulation results show that the hybrid Izhikevich neuron model is capable of capturing many of the dynamical properties of the basal ganglia-thalamic neuronal network, such as variations of the firing rates and emergence of synchronous oscillations under the Parkinsonian condition, despite the simplicity of the two-dimensional neuronal model. It may suggest that the computational efficient hybrid Izhikevich neuron model can be used to explore basal ganglia normal and abnormal functions. Especially it provides an efficient way of emulating the large-scale neuron network

  17. Effective connectivity of ascending and descending frontal-thalamic pathways during sustained attention: Complex brain network interactions in adolescence

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    Jagtap, Pranav; Diwadkar, Vaibhav A.

    2016-01-01

    Frontal-thalamic interactions are crucial for bottom-up gating and top-down control, yet have not been well studied from brain network perspectives. We applied network modeling of fMRI signals (Dynamic Causal Modeling; DCM) to investigate frontal-thalamic interactions during an attention task with parametrically varying levels of demand. fMRI was collected while subjects participated in a sustained continuous performance task with low and high attention demands. 162 competing model architectu...

  18. Intrinsic properties of and thalamocortical inputs onto identified corticothalamic-VPM neurons.

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    Yang, Qizong; Chen, Chia-Chien; Ramos, Raddy L; Katz, Elizabeth; Keller, Asaf; Brumberg, Joshua C

    2014-06-01

    Corticothalamic (CT) feedback plays an important role in regulating the sensory information that the cortex receives. Within the somatosensory cortex layer VI originates the feedback to the ventral posterior medial (VPM) nucleus of the thalamus, which in turn receives sensory information from the contralateral whiskers. We examined the physiology and morphology of CT neurons in rat somatosensory cortex, focusing on the physiological characteristics of the monosynaptic inputs that they receive from the thalamus. To identify CT neurons, rhodamine microspheres were injected into VPM and allowed to retrogradely transport to the soma of CT neurons. Thalamocortical slices were prepared at least 3 days post injection. Whole-cell recordings from labeled CT cells in layer VI demonstrated that they are regular spiking neurons and exhibit little spike frequency adaption. Two anatomical classes were identified based on their apical dendrites that either terminated by layer V (compact cells) or layer IV (elaborate cells). Thalamic inputs onto identified CT-VPM neurons demonstrated paired pulse depression over a wide frequency range (2-20 Hz). Stimulus trains also resulted in significant synaptic depression above 10 Hz. Our results suggest that thalamic inputs differentially impact CT-VPM neurons in layer VI. This characteristic may allow them to differentiate a wide range of stimulation frequencies which in turn further tune the feedback signals to the thalamus.

  19. Distinct temporal spike and local field potential activities in the thalamic parafascicular nucleus of parkinsonian rats during rest and limb movement.

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    Wang, Min; Qu, Qingyang; He, Tingting; Li, Min; Song, Zhimin; Chen, Feiyu; Zhang, Xiao; Xie, Jinlu; Geng, Xiwen; Yang, Maoquan; Wang, Xiusong; Lei, Chengdong; Hou, Yabing

    2016-08-25

    Several studies have suggested that the thalamic centromedian-parafascicular (CM/PF or the PF in rodents) is implicated in the pathophysiology of Parkinson's disease (PD). However, inconsistent changes in the neuronal firing rate and pattern have been reported in parkinsonian animals. To investigate the impact of a dopaminergic cell lesion on PF extracellular discharge in behaving rats, the PF neural activities in the spike and local field potential (LFP) were recorded in unilaterally 6-hydroxydopamine- (6-OHDA) lesioned and neurologically intact control rats during rest and limb movement. During rest, the two PF neuronal subtypes was less spontaneously active, with no difference in the spike firing rates between the control and lesioned rats; only the lesioned rats reshaped their spike firing pattern. Furthermore, the simultaneously recorded LFP in the lesioned rats exhibited a significant increase in power at 12-35 and 35-70Hz and a decrease in power at 0.7-12Hz. During the execution of a voluntary movement, two subtypes of PF neurons were identified by a rapid increase in the discharge activity in both the control and lesioned rats. However, dopamine lesioning was associated with a decrease in neuronal spiking fire rate and reshaping in the firing pattern in the PF. The simultaneously recorded LFP activity exhibited a significant increase in power at 12-35Hz and a decrease in power at 0.7-12Hz compared with the control rats. These findings indicate that 6-OHDA induces modifications in PF spike and LFP activities in rats during rest and movement and suggest that PF dysfunction may be an important contributor to the pathophysiology of parkinsonian motor impairment. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. Control of Absence Seizures by the Thalamic Feed-Forward Inhibition.

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    Chen, Mingming; Guo, Daqing; Xia, Yang; Yao, Dezhong

    2017-01-01

    As a subtype of idiopathic generalized epilepsies, absence epilepsy is believed to be caused by pathological interactions within the corticothalamic (CT) system. Using a biophysical mean-field model of the CT system, we demonstrate here that the feed-forward inhibition (FFI) in thalamus, i.e., the pathway from the cerebral cortex (Ctx) to the thalamic reticular nucleus (TRN) and then to the specific relay nuclei (SRN) of thalamus that are also directly driven by the Ctx, may participate in controlling absence seizures. In particular, we show that increasing the excitatory Ctx-TRN coupling strength can significantly suppress typical electrical activities during absence seizures. Further, investigation demonstrates that the GABAA- and GABAB-mediated inhibitions in the TRN-SRN pathway perform combination roles in the regulation of absence seizures. Overall, these results may provide an insightful mechanistic understanding of how the thalamic FFI serves as an intrinsic regulator contributing to the control of absence seizures.

  1. Hypofractionated Stereotactic Radiosurgery in a Large Bilateral Thalamic and Basal Ganglia Arteriovenous Malformation

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    Janet Lee

    2013-01-01

    Full Text Available Purpose. Arteriovenous malformations (AVMs in the basal ganglia and thalamus have a more aggressive natural history with a higher morbidity and mortality than AVMs in other locations. Optimal treatment—complete obliteration without new neurological deficits—is often challenging. We present a patient with a large bilateral basal ganglia and thalamic AVM successfully treated with hypofractionated stereotactic radiosurgery (HFSRS with intensity modulated radiotherapy (IMRT. Methods. The patient was treated with hypofractionated stereotactic radiosurgery to 30 Gy at margin in 5 fractions of 9 static fields with a minimultileaf collimator and intensity modulated radiotherapy. Results. At 10 months following treatment, digital subtraction angiography showed complete obliteration of the AVM. Conclusions. Large bilateral thalamic and basal ganglia AVMs can be successfully treated with complete obliteration by HFSRS with IMRT with relatively limited toxicity. Appropriate caution is recommended.

  2. Memory Profiles after Unilateral Paramedian Thalamic Stroke Infarction: A Comparative Study

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    Antonio Carota

    2015-01-01

    Full Text Available We performed extensive neuropsychological assessment of two male patients (matched for age and educational level with similar (localization and size unilateral paramedian ischemic thalamic lesions (AB on the left and SD on the right. Both patients showed severe memory impairments as well as other cognitive deficits. In comparison to SD, AB showed severe impairment of executive functions and a more severe deficit of episodic/anterograde memory, especially in the verbal modality. The findings of this single case study suggest the possibility that the profile and severity of the executive dysfunction are determinant for the memory deficits and depend on from the side of the lesion. In addition to a material-side-specific (verbal versus visual deficit hypothesis, the differential diencephalo-prefrontal contributions in mnestic-processing, in case of paramedian thalamic stroke, might also be explained in terms of their stage-specificity (encoding versus retrieval.

  3. STDP in recurrent neuronal networks

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    Matthieu Gilson

    2010-09-01

    Full Text Available Recent results about spike-timing-dependent plasticity (STDP in recurrently connected neurons are reviewed, with a focus on the relationship between the weight dynamics and the emergence of network structure. In particular, the evolution of synaptic weights in the two cases of incoming connections for a single neuron and recurrent connections are compared and contrasted. A theoretical framework is used that is based upon Poisson neurons with a temporally inhomogeneous firing rate and the asymptotic distribution of weights generated by the learning dynamics. Different network configurations examined in recent studies are discussed and an overview of the current understanding of STDP in recurrently connected neuronal networks is presented.

  4. Surgical resection of unilateral thalamic tumors in adults: approaches and outcomes.

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    Cao, Lei; Li, Chuzhong; Zhang, Yazhuo; Gui, Songbai

    2015-11-07

    The thalamic tumors were less common in adults and this study aimed to determine the clinical features, surgical approaches, and outcomes of adult thalamic tumors, which have not been well-described in the literature. We reviewed the clinical presentation, surgical approach, perioperative mortality and morbidity, and outcomes of 111 operated patients (71 males, 40 females; mean age at presentation, 33.4 ± 13.2 years) with unilateral thalamic tumor. The most common clinical presentations were increased intracranial pressure (65%) and motor deficits (40%). Five surgical approaches were used depending on tumor location; the most common was the transparieto-occipital approach (47.7%). According to peri- and post-operative magnetic resonance imaging findings, the tumors were totally resected in 29 cases (26.1%), subtotally resected in 54 cases (48.6%), and partially resected in 21 cases (18.9%). Five patients died during the perioperative period (4.5%, 5/111). The most common morbidity was motor deficits (21.7%, 23/106). According to histological findings, there were 50 high-grade and 61 low-grade tumors. Median survival of patients with low- and high-grade tumors were 40 and 12 months, respectively (mean follow-up, 37.3 months). Survival was significantly longer in cases of total or subtotal resection (median, 28 months) compared to partial resection or biopsy (median, 12 months). Survival was poorer in adults than in previous reported pediatrics. Surgical treatment of adult thalamic tumors must be individualized according to tumor location. Low-grade tumors and total/subtotal resection seem to be predictors of better surgical outcomes. Nevertheless, the outcome of adult patients were still worse than pediatric patients.

  5. Noisy Neurons

    Indian Academy of Sciences (India)

    IAS Admin

    Nerves are fibres that conduct electrical signals and hence pass on information from and to the brain. Nerves are made of nerve cells called neurons (Figure 1). Instructions in our body are sent via electrical signals that present themselves as variations in the potential across neuronal membranes. These potential differences ...

  6. Motor Neurons

    DEFF Research Database (Denmark)

    Hounsgaard, Jorn

    2017-01-01

    Motor neurons translate synaptic input from widely distributed premotor networks into patterns of action potentials that orchestrate motor unit force and motor behavior. Intercalated between the CNS and muscles, motor neurons add to and adjust the final motor command. The identity and functional...

  7. Cognitive consequences of thalamic, basal ganglia, and deep white matter lacunes in brain aging and dementia.

    Science.gov (United States)

    Gold, Gabriel; Kövari, Enikö; Herrmann, François R; Canuto, Alessandra; Hof, Patrick R; Michel, Jean-Pierre; Bouras, Constantin; Giannakopoulos, Panteleimon

    2005-06-01

    Most previous studies addressed the cognitive impact of lacunar infarcts using radiologic correlations that are known to correlate poorly with neuropathological data. Moreover, absence of systematic bilateral assessment of vascular lesions and masking effects of Alzheimer disease pathology and macrovascular lesions may explain discrepancies among previous reports. To define the relative contribution of silent lacunes to cognitive decline, we performed a detailed analysis of lacunar and microvascular pathology in both cortical and subcortical areas of 72 elderly individuals without significant neurofibrillary tangle pathology or macrovascular lesions. Cognitive status was assessed prospectively using the Clinical Dementia Rating (CDR) scale; neuropathological evaluation included Abeta-protein deposition staging and bilateral assessment of microvascular ischemic pathology and lacunes; statistical analysis included multivariate models controlling for age, amyloid deposits, and microvascular pathology. Thalamic and basal ganglia lacunes were negatively associated with CDR scores; cortical microinfarcts, periventricular and diffuse white matter demyelination also significantly affected cognition. In a multivariate model, cortical microinfarcts and thalamic and basal ganglia lacunes explained 22% of CDR variability; amyloid deposits and microvascular pathology explained 12%, and the assessment of thalamic and basal ganglia lacunes added an extra 17%. Deep white matter lacunes were not related to cognitive status in univariate and multivariate models. In agreement with the recently proposed concept of subcortical ischemic vascular dementia, our autopsy series provides important evidence that gray matter lacunes are independent predictors of cognitive decline in elderly individuals without concomitant dementing processes such as Alzheimer disease.

  8. Left Dorsomedial Thalamic Damage Impairs Verbal Recall More Than Recognition: A Case Report.

    Science.gov (United States)

    Ruggeri, Massimiliano

    2016-09-01

    Damage to the dorsomedial thalamus usually leads to impaired episodic memory, attention, and executive function, but the role of the dorsomedial thalamus in memory processing is still not fully understood. Clinical evidence is inconclusive about whether dorsomedial thalamic damage impairs recall or whether it impairs recognition. I report a unique patient who suffered a cardioembolic stroke in the paramedian artery territory, caused by a patent foramen ovale. He was left with a chronic ischemic lesion centered in the parvocellular and, to a lesser extent, the magnocellular portions of the left dorsomedial thalamic nucleus, and marginally involving the midline and intralaminar nuclei. A year after the stroke, the patient's neuropsychological assessment showed a selective verbal memory deficit with greater loss of recall than recognition. His memory was normal when he was given semantically encoded material. His test results showed that damage to the left dorsomedial thalamic nucleus might affect both his recall and recognition because of the involvement of the parvocellular and magnocellular portions, respectively. The results also suggest that the left dorsomedial thalamus is involved in the encoding of verbal material. This case report highlights the role that the left dorsomedial thalamus plays in processing memory specific to verbal material. The findings point to the differential contribution of the dorsomedial parvocellular nucleus to recall, and support the theory that prefrontal strategic memory is enabled by adequate encoding of information through thalamocortical connectivity with the dorsolateral prefrontal cortex.

  9. Impact of cannabis use on thalamic volume in people at familial high risk of schizophrenia.

    Science.gov (United States)

    Welch, Killian A; Stanfield, Andrew C; McIntosh, Andrew M; Whalley, Heather C; Job, Dominic E; Moorhead, Thomas W; Owens, David G C; Lawrie, Stephen M; Johnstone, Eve C

    2011-11-01

    No longitudinal study has yet examined the association between substance use and brain volume changes in a population at high risk of schizophrenia. To examine the effects of cannabis on longitudinal thalamus and amygdala-hippocampal complex volumes within a population at high risk of schizophrenia. Magnetic resonance imaging scans were obtained from individuals at high genetic risk of schizophrenia at the point of entry to the Edinburgh High-Risk Study (EHRS) and approximately 2 years later. Differential thalamic and amygdala-hippocampal complex volume change in high-risk individuals exposed (n = 25) and not exposed (n = 32) to cannabis in the intervening period was investigated using repeated-measures analysis of variance. Cannabis exposure was associated with bilateral thalamic volume loss. This effect was significant on the left (F = 4.47, P = 0.04) and highly significant on the right (F= 7.66, P= 0.008). These results remained significant when individuals using other illicit drugs were removed from the analysis. These are the first longitudinal data to demonstrate an association between thalamic volume loss and exposure to cannabis in currently unaffected people at familial high risk of developing schizophrenia. This observation may be important in understanding the link between cannabis exposure and the subsequent development of schizophrenia.

  10. Disrupted Auto-Activation, Dysexecutive and Confabulating Syndrome Following Bilateral Thalamic and Right Putaminal Stroke

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    Lieve De Witte

    2008-01-01

    Full Text Available Objective: Clinical, neuropsychological, structural and functional neuroimaging results are reported in a patient who developed a unique combination of symptoms after a bi-thalamic and right putaminal stroke. The symptoms consisted of dysexecutive disturbances associated with confabulating behavior and auto-activation deficits. Background: Basal ganglia and thalamic lesions may result in a variety of motor, sensory, neuropsychological and behavioral syndromes. However, the combination of a dysexecutive syndrome complicated at the behavioral level with an auto-activation and confabulatory syndrome has never been reported. Methods: Besides clinical and neuroradiological investigations, an extensive set of standardized neuropsychological tests was carried out. Results: In the post-acute phase of the stroke, a dysexecutive syndrome was found in association with confabulating behavior and auto-activation deficits. MRI showed focal destruction of both thalami and the right putamen. Quantified ECD SPECT revealed bilateral hypoperfusions in the basal ganglia and thalamus but no perfusion deficits were found at the cortical level. Conclusion: The combination of disrupted auto-activation, dysexecutive and confabulating syndrome in a single patient following isolated subcortical damage renders this case exceptional. Although these findings do not reveal a functional disruption of the striato-ventral pallidal-thalamic-frontomesial limbic circuitry, they add to the understanding of the functional role of the basal ganglia in cognitive and behavioral syndromes.

  11. Bilateral thalamic deep brain stimulation for the treatment of head tremor. Report of two cases.

    Science.gov (United States)

    Berk, Caglar; Honey, Christopher R

    2002-03-01

    Isolated head tremor is rare, but can be disabling. The authors' experience with the treatment of limb tremor due to essential tremor led them to consider using bilateral thalamic deep brain stimulation (DBS) in two patients presenting only with disabling head tremor. One patient exhibited no peripheral tremor and the other displayed only a slight upper-limb tremor. Both patients underwent placement of units that apply simultaneous bilateral thalamic DBS. Surgical targets were verified by using intraoperative macrostimulation, and the stimulators were implanted during the same surgery. Patients were videotaped preoperatively and at 2, 4, 6, and 9 months postoperatively during periods in which the stimulators were turned on and off. Videotapes were randomized and rated for resting, postural, and action tremors according to the Fahn clinical rating scale for tremor. Because this scale is not designed for head tremor, the patients were also evaluated on the basis of a functional scale that reflected their quality of life and the amount of disability caused by head tremor. Both patients experienced no tremor after their stimulators were turned on and properly adjusted at the 6th postoperative week. The patients were followed for a total of 9 months and results remained stable throughout this period. No complications were encountered. Bilateral thalamic DBS appears to be an effective and safe treatment for isolated head tremor in patients with essential tremor. The authors present a scale for the functional assessment of head tremor.

  12. OCCLUSION OF ARTERY OF PERCHERON: A RARE AETIOLOGY OF BILATERAL THALAMIC INFARCT

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    Mane Makarand, Mane Priyanka, Mohite Rajsinh , Bhattad Prashant, Bangar Kushal, Mahajani Anup

    2015-10-01

    Full Text Available The Artery of Percheron, a rare anatomical variant of brain vascularisation, arises from the posterior cerebral artery. Occlusion of this artery leads to bilateral paramedian thalamic infarct leads to dysfunction of central nervous system. Incidence of bilateral thalamic infarct secondary to occlusion of artery of Percheron is unknown because of its rarity. Here we report a case of 35 year old female presented with altered state of consciousness and the underlying cause was occlusion of Artery of Percheron which leads to bilateral thalamic infarct detected on MRI scanning. It showed hyperintensities on T2W1 and FLAIR, and hypointensity on T1W1, restricted to bilateral ventromedial thalami showing corresponding area of high signal intensity on diffusion weighted images and hypointensity on apparent diffusion coefficient images indicating diffusion restriction, suggestive of infarct. On further investigation magnetic resonance arteriogram (MRA of the brain demonstrated a single common artery arising from the left P1 segment which divided into two branches distally supplying bilateral thalami. Patient became alright after 2 weeks of medical line of treatment.

  13. Reduced thalamic volume in Parkinson disease with REM sleep behavior disorder: volumetric study.

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    Salsone, M; Cerasa, A; Arabia, G; Morelli, M; Gambardella, A; Mumoli, L; Nisticò, R; Vescio, B; Quattrone, A

    2014-09-01

    REM sleep behavior disorder (RBD) is a common non motor feature of Parkinson's Disease (PD) affecting about half the patients with this disease. Distinct structural brain tissue abnormalities have been reported in several regions modulating REM sleep of the patients with idiopathic RBD. At the present time, there are no conventional MRI studies investigating patients with PD associated with RBD. Herein, we used voxel-based morphometry (VBM) to detect the neuroanatomical profile of PD patients with and without RBD. Optimized VBM was applied to the MRI brain images in 11 PD patients with RBD (PD-RBD), 11 PD patients without RBD (PD) and 18 age-and sex-matched controls. To corroborate VBM findings we used automated volumetric method (FreeSurfer) to quantify subcortical brain regions volumes. Patients and controls also underwent DAT-SPECT and cardiac MIBG scintigraphies. The VBM analysis showed markedly reduced gray matter volume in the right thalamus of PD-RBD patients in comparison with PD patients and controls. Automatic thalamic segmentation in PD-RBD patients showed a bilaterally reduced thalamic volume as compared with PD patients or controls. All PD patients (with and without RBD) showed a reduced tracer uptake on DAT-SPECT and cardiac MIBG scintigraphies as compared to controls. Our findings suggest that the presence of RBD symptoms in PD patients is associated with a reduced thalamic volume suggesting a pathophysiologic role of the thalamus in the complex circuit causing RBD. Copyright © 2014. Published by Elsevier Ltd.

  14. Decreased Numbers of Somatostatin-Expressing Neurons in the Amygdala of Subjects With Bipolar Disorder or Schizophrenia: Relationship to Circadian Rhythms.

    Science.gov (United States)

    Pantazopoulos, Harry; Wiseman, Jason T; Markota, Matej; Ehrenfeld, Lucy; Berretta, Sabina

    2017-03-15

    Growing evidence points to a key role for somatostatin (SST) in schizophrenia (SZ) and bipolar disorder (BD). In the amygdala, neurons expressing SST play an important role in the regulation of anxiety, which is often comorbid in these disorders. We tested the hypothesis that SST-immunoreactive (IR) neurons are decreased in the amygdala of subjects with SZ and BD. Evidence for circadian SST expression in the amygdala and disrupted circadian rhythms and rhythmic peaks of anxiety in BD suggest a disruption of rhythmic expression of SST in this disorder. Amygdala sections from 12 SZ, 15 BD, and 15 control subjects were processed for immunocytochemistry for SST and neuropeptide Y, a neuropeptide partially coexpressed in SST-IR neurons. Total numbers (N t ) of IR neurons were measured. Time of death was used to test associations with circadian rhythms. SST-IR neurons were decreased in the lateral amygdala nucleus in BD (N t , p = .003) and SZ (N t , p = .02). In normal control subjects, N t of SST-IR neurons varied according to time of death. This pattern was altered in BD subjects, characterized by decreases of SST-IR neurons selectively in subjects with time of death corresponding to the day (6:00 am to 5:59 pm). Numbers of neuropeptide Y-IR neurons were not affected. Decreased SST-IR neurons in the amygdala of patients with SZ and BD, interpreted here as decreased SST expression, may disrupt responses to fear and anxiety regulation in these individuals. In BD, our findings raise the possibility that morning peaks of anxiety depend on a disruption of circadian regulation of SST expression in the amygdala. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  15. SDF1-CXCR4 Signaling Maintains Central Post-Stroke Pain through Mediation of Glial-Neuronal Interactions

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    Fei Yang

    2017-07-01

    Full Text Available Central post-stroke pain (CPSP is an intractable central neuropathic pain that has been poorly studied mechanistically. Here we showed that stromal cell-derived factor 1 (SDF1 or CXCL12, a member of the CXC chemokine family, and its receptor CXCR4 played a key role in the development and maintenance of thalamic hemorrhagic CPSP through hypoxia inducible factor 1α (HIF-1α mediated microglial-astrocytic-neuronal interactions. First, both intra-thalamic collagenase (ITC and SDF1 injections could induce CPSP that was blockable and reversible by intra-thalamic administration of both AMD3100 (a selective CXCR4 antagonist and inhibitors of microglial or astrocytic activation. Second, long-term increased-expression of SDF1 and CXCR4 that was accompanied by activations of both microglia and astrocytes following ITC could be blocked by both AMD-3100 and YC-1, a selective inhibitor of HIF-1α. AMD-3100 could also inhibit release of proinflammatory mediators (TNFα, IL1β and IL-6. Increased-expression of HIF-1α, SDF1, CXCR4, Iba1 and GFAP proteins could be induced by both ITC and intra-thalamic CoCl2, an inducer of HIF-1α that was blockable by both HIF-1α inhibition and CXCR4 antagonism. Finally, inhibition of HIF-1α was only effective in prevention, but not in treatment of ITC-induced CPSP. Taken together, the present study demonstrated that in the initial process of thalamic hemorrhagic state HIF-1α up-regulated SDF1-CXCR4 signaling, while in the late process SDF1-CXCR4 signaling-mediated positive feedback plays more important role in glial-glial and glial-neuronal interactions and might be a novel promising molecular target for treatment of CPSP in clinic.

  16. Thalamic haemorrhage vs internal capsule-basal ganglia haemorrhage: clinical profile and predictors of in-hospital mortality

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    García-Eroles Luis

    2007-10-01

    Full Text Available Abstract Background There is a paucity of clinical studies focused specifically on intracerebral haemorrhages of subcortical topography, a subject matter of interest to clinicians involved in stroke management. This single centre, retrospective study was conducted with the following objectives: a to describe the aetiological, clinical and prognostic characteristics of patients with thalamic haemorrhage as compared with that of patients with internal capsule-basal ganglia haemorrhage, and b to identify predictors of in-hospital mortality in patients with thalamic haemorrhage. Methods Forty-seven patients with thalamic haemorrhage were included in the "Sagrat Cor Hospital of Barcelona Stroke Registry" during a period of 17 years. Data from stroke patients are entered in the stroke registry following a standardized protocol with 161 items regarding demographics, risk factors, clinical features, laboratory and neuroimaging data, complications and outcome. The region of the intracranial haemorrhage was identified on computerized tomographic (CT scans and/or magnetic resonance imaging (MRI of the brain. Results Thalamic haemorrhage accounted for 1.4% of all cases of stroke (n = 3420 and 13% of intracerebral haemorrhage (n = 364. Hypertension (53.2%, vascular malformations (6.4%, haematological conditions (4.3% and anticoagulation (2.1% were the main causes of thalamic haemorrhage. In-hospital mortality was 19% (n = 9. Sensory deficit, speech disturbances and lacunar syndrome were significantly associated with thalamic haemorrhage, whereas altered consciousness (odds ratio [OR] = 39.56, intraventricular involvement (OR = 24.74 and age (OR = 1.23, were independent predictors of in-hospital mortality. Conclusion One in 8 patients with acute intracerebral haemorrhage had a thalamic hematoma. Altered consciousness, intraventricular extension of the hematoma and advanced age were determinants of a poor early outcome.

  17. Layer 6 Corticothalamic Neurons Activate a Cortical Output Layer, Layer 5a

    Science.gov (United States)

    Kim, Juhyun; Matney, Chanel J.; Blankenship, Aaron; Hestrin, Shaul

    2014-01-01

    Layer 6 corticothalamic neurons are thought to modulate incoming sensory information via their intracortical axons targeting the major thalamorecipient layer of the neocortex, layer 4, and via their long-range feedback projections to primary sensory thalamic nuclei. However, anatomical reconstructions of individual layer 6 corticothalamic (L6 CT) neurons include examples with axonal processes ramifying within layer 5, and the relative input of the overall population of L6 CT neurons to layers 4 and 5 is not well understood. We compared the synaptic impact of L6 CT cells on neurons in layers 4 and 5. We found that the axons of L6 CT neurons densely ramified within layer 5a in both visual and somatosensory cortices of the mouse. Optogenetic activation of corticothalamic neurons generated large EPSPs in pyramidal neurons in layer 5a. In contrast, excitatory neurons in layer 4 exhibited weak excitation or disynaptic inhibition. Fast-spiking parvalbumin-positive cells in both layer 5a and layer 4 were also strongly activated by L6 CT neurons. The overall effect of L6 CT activation was to suppress layer 4 while eliciting action potentials in layer 5a pyramidal neurons. Together, our data indicate that L6 CT neurons strongly activate an output layer of the cortex. PMID:25031405

  18. Persistent Thalamic Sound Processing Despite Profound Cochlear Denervation

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    Anna R. Chambers

    2016-08-01

    Full Text Available Neurons at higher stages of sensory processing can partially compensate for a sudden drop in input from the periphery through a homeostatic plasticity process that increases the gain on weak afferent inputs. Even after a profound unilateral auditory neuropathy where > 95% of synapses between auditory nerve fibers and inner hair cells have been eliminated with ouabain, central gain can restore the cortical processing and perceptual detection of basic sounds delivered to the denervated ear. In this model of profound auditory neuropathy, cortical processing and perception recover despite the absence of an auditory brainstem response (ABR or brainstem acoustic reflexes, and only a partial recovery of sound processing at the level of the inferior colliculus (IC, an auditory midbrain nucleus. In this study, we induced a profound cochlear neuropathy with ouabain and asked whether central gain enabled a compensatory plasticity in the auditory thalamus comparable to the full recovery of function previously observed in the auditory cortex (ACtx, the partial recovery observed in the IC, or something different entirely. Unilateral ouabain treatment in adult mice effectively eliminated the ABR, yet robust sound-evoked activity persisted in a minority of units recorded from the contralateral medial geniculate body (MGB of awake mice. Sound-driven MGB units could decode moderate and high-intensity sounds with accuracies comparable to sham-treated control mice, but low-intensity classification was near chance. Pure tone receptive fields and synchronization to broadband pulse trains also persisted, albeit with significantly reduced quality and precision, respectively. MGB decoding of temporally modulated pulse trains and speech tokens were both greatly impaired in ouabain-treated mice. Taken together, the absence of an ABR belied a persistent auditory processing at the level of the MGB that was likely enabled through increased central gain. Compensatory

  19. Impairment in material-specific long-term memory following unilateral mediodorsal thalamic damage and presumed partial disconnection of the mammillo-thalamic tract.

    Science.gov (United States)

    Edelstyn, Nicola M J; Mayes, Andrew R; Denby, Christine; Ellis, Simon J

    2012-03-01

    Neuropsychological findings suggest material-specific lateralization of the medial temporal lobe's role in long-term memory, with greater left-sided involvement in verbal memory, and greater right-sided involvement in visual memory. Whether material-specific lateralization of long-term memory also extends to the anteromedial thalamus remains uncertain. We report two patients with unilateral right (OG) and left (SM) mediodorsal thalamic pathology plus probable correspondingly lateralized damage of the mammillo-thalamic tract. The lesions were mapped using high-resolution structural magnetic resonance imaging and schematically reconstructed. Mean absolute volume estimates for the mammillary bodies, hippocampus, perirhinal cortex, and ventricles are also presented. Estimates of visual and verbal recall and item recognition memory were obtained using the Doors and People, the Rey Complex Figure Test, and the Logical Memory subtests of the Wechsler Memory Scales. Each patient's performance was compared to a group of healthy volunteers matched for demographic characteristics, premorbid IQ, and current levels of functioning. A striking double dissociation was evident in material-specific long-term memory, with OG showing significant impairments in visual memory but not verbal memory, and SM showing the opposite profile of preserved visual memory and significantly impaired verbal memory. These impairments affected both recall and item recognition. The reported double dissociation provides the strongest evidence yet that material-specific lateralization of long-term memory also extends to the anteromedial thalamus. The findings are also discussed in relation to proposals that distinct anatomical regions within the medial temporal lobe, anteromedial thalamus, and associated tracts make qualitatively different contributions to recall and item recognition. ©2011 The British Psychological Society.

  20. Perturbation of Serotonin Homeostasis during Adulthood Affects Serotonergic Neuronal Circuitry.

    Science.gov (United States)

    Pratelli, Marta; Migliarini, Sara; Pelosi, Barbara; Napolitano, Francesco; Usiello, Alessandro; Pasqualetti, Massimo

    2017-01-01

    Growing evidence shows that the neurotransmitter serotonin (5-HT) modulates the fine-tuning of neuron development and the establishment of wiring patterns in the brain. However, whether serotonin is involved in the maintenance of neuronal circuitry in the adult brain remains elusive. Here, we use a Tph2(fl)°(x) conditional knockout (cKO) mouse line to assess the impact of serotonin depletion during adulthood on serotonergic system organization. Data show that the density of serotonergic fibers is increased in the hippocampus and decreased in the thalamic paraventricular nucleus (PVN) as a consequence of brain serotonin depletion. Strikingly, these defects are rescued following reestablishment of brain 5-HT signaling via administration of the serotonin precursor 5-hydroxytryptophan (5-HTP). Finally, 3D reconstruction of serotonergic fibers reveals that changes in serotonin homeostasis affect axonal branching complexity. These data demonstrate that maintaining proper serotonin homeostasis in the adult brain is crucial to preserve the correct serotonergic axonal wiring.

  1. Effect of ionizing radiation in sensory ganglion neurons: organization and dynamics of nuclear compartments of DNA damage/repair and their relationship with transcription and cell cycle.

    Science.gov (United States)

    Casafont, Iñigo; Palanca, Ana; Lafarga, Vanesa; Berciano, Maria T; Lafarga, Miguel

    2011-10-01

    Neurons are very sensitive to DNA damage induced by endogenous and exogenous genotoxic agents, as defective DNA repair can lead to neurodevelopmental disorders, brain tumors and neurodegenerative diseases with severe clinical manifestations. Understanding the impact of DNA damage/repair mechanisms on the nuclear organization, particularly on the regulation of transcription and cell cycle, is essential to know the pathophysiology of defective DNA repair syndromes. In this work, we study the nuclear architecture and spatiotemporal organization of chromatin compartments involved in the DNA damage response (DDR) in rat sensory ganglion neurons exposed to X-ray irradiation (IR). We demonstrate that the neuronal DDR involves the formation of two categories of DNA-damage processing chromatin compartments: transient, disappearing within the 1 day post-IR, and persistent, where unrepaired DNA is accumulated. Both compartments concentrate components of the DDR pathway, including γH2AX, pATM and 53BP1. Furthermore, DNA damage does not induce neuronal apoptosis but triggers the G0-G1 cell cycle phase transition, which is mediated by the activation of the ATM-p53 pathway and increased protein levels of p21 and cyclin D1. Moreover, the run on transcription assay reveals a severe inhibition of transcription at 0.5 h post-IR, followed by its rapid recovery over the 1 day post-IR in parallel with the progression of DNA repair. Therefore, the response of healthy neurons to DNA damage involves a transcription- and cell cycle-dependent but apoptosis-independent process. Furthermore, we propose that the segregation of unrepaired DNA in a few persistent chromatin compartments preserves genomic stability of undamaged DNA and the global transcription rate in neurons.

  2. Thalamic metabolic alterations with cognitive dysfunction in idiopathic trigeminal neuralgia: a multivoxel spectroscopy study

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    Wang, Yuan; Bao, Faxiu; Ma, Shaohui; Guo, Chenguang; Jin, Chenwang; Zhang, Ming [First Affiliated Hospital of Xi' an Jiaotong University, Department of Medical Imaging, Xi' an, Shaanxi (China); Li, Dan [First Affiliated Hospital of Xi' an Jiaotong University, Department of Respiratory and Critical Care Medicine, Xi' an, Shaanxi (China)

    2014-08-15

    Although abnormalities in metabolite compositions in the thalamus are well described in patients with idiopathic trigeminal neuralgia (ITN), differences in distinct thalamic subregions have not been measured with proton magnetic resonance spectroscopy ({sup 1}H-MRS), and whether there are correlations between thalamic metabolites and cognitive function still remain unknown. Multivoxel MRS was recorded to investigate the metabolic alterations in the thalamic subregions of patients with ITN. The regions of interest were localized in the anterior thalamus (A-Th), intralaminar portion of the thalamus (IL-Th), posterior lateral thalamus (PL-Th), posterior medial thalamus (PM-Th), and medial and lateral pulvinar of the thalamus (PuM-Th and PuL-Th). The N-acetylaspartate to creatine (NAA/Cr) and choline to creatine (Cho/Cr) ratios were measured in the ITN and control groups. Scores of the visual analogue scale (VAS) and the Montreal Cognitive Assessment (MoCA) were analyzed to correlate with the neuroradiological findings. The NAA/Cr ratio in the affected side of PM-Th and PL-Th in ITN patients was statistically lower than that in the corresponding regions of the thalamus in controls. The NAA/Cr ratio in the affected PM-Th was negatively associated with VAS and disease duration. Furthermore, decreases of NAA/Cr and Cho/Cr were detected in the affected side of IL-Th, and lower Cho/Cr was positively correlated with MoCA values in the ITN group. Our result of low level of NAA/Cr in the affected PM-Th probably serves as a marker of the pain-rating index, and decreased Cho/Cr in IL-Th may be an indicator of cognitive disorder in patients with ITN. (orig.)

  3. Thalamic GABA predicts fine motor performance in manganese-exposed smelter workers.

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    Zaiyang Long

    Full Text Available Overexposure to manganese (Mn may lead to parkinsonian symptoms including motor deficits. The main inhibitory neurotransmitter gamma-aminobutyric acid (GABA is known to play a pivotal role in the regulation and performance of movement. Therefore this study was aimed at testing the hypothesis that an alteration of GABA following Mn exposure may be associated with fine motor performance in occupationally exposed workers and may underlie the mechanism of Mn-induced motor deficits. A cohort of nine Mn-exposed male smelter workers from an Mn-iron alloy factory and 23 gender- and age-matched controls were recruited and underwent neurological exams, magnetic resonance spectroscopy (MRS measurements, and Purdue pegboard motor testing. Short-echo-time MRS was used to measure N-Acetyl-aspartate (NAA and myo-inositol (mI. GABA was detected with a MEGA-PRESS J-editing MRS sequence. The mean thalamic GABA level was significantly increased in smelter workers compared to controls (p = 0.009. Multiple linear regression analysis reveals (1 a significant association between the increase in GABA level and the duration of exposure (R(2 = 0.660, p = 0.039, and (2 significant inverse associations between GABA levels and all Purdue pegboard test scores (for summation of all scores R(2 = 0.902, p = 0.001 in the smelter workers. In addition, levels of mI were reduced significantly in the thalamus and PCC of smelter workers compared to controls (p = 0.030 and p = 0.009, respectively. In conclusion, our results show clear associations between thalamic GABA levels and fine motor performance. Thus in Mn-exposed subjects, increased thalamic GABA levels may serve as a biomarker for subtle deficits in motor control and may become valuable for early diagnosis of Mn poisoning.

  4. Anatomical substrates for direct interactions between hippocampus, medial prefrontal cortex, and the thalamic nucleus reuniens

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    Varela, C.; Kumar, S.; Yang, J. Y.; Wilson, M. A.

    2014-01-01

    The reuniens nucleus in the midline thalamus projects to the medial prefrontal cortex (mPFC) and the hippocampus, and has been suggested to modulate interactions between these regions, such as spindle–ripple correlations during sleep and theta band coherence during exploratory behavior. Feedback from the hippocampus to the nucleus reuniens has received less attention but has the potential to influence thalamocortical networks as a function of hippocampal activation. We used the retrograde tracer cholera toxin B conjugated to two fluorophores to study thalamic projections to the dorsal and ventral hippocampus and to the prelimbic and infralimbic subregions of mPFC. We also examined the feedback connections from the hippocampus to reuniens. The goal was to evaluate the anatomical basis for direct coordination between reuniens, mPFC, and hippocampus by looking for double-labeled cells in reuniens and hippocampus. In confirmation of previous reports, the nucleus reuniens was the origin of most thalamic afferents to the dorsal hippocampus, whereas both reuniens and the lateral dorsal nucleus projected to ventral hippocampus. Feedback from hippocampus to reuniens originated primarily in the dorsal and ventral subiculum. Thalamic cells with collaterals to mPFC and hippocampus were found in reuniens, across its anteroposterior axis, and represented, on average, about 8 % of the labeled cells in reuniens. Hippocampal cells with collaterals to mPFC and reuniens were less common (~1 % of the labeled subicular cells), and located in the molecular layer of the subiculum. The results indicate that a subset of reuniens cells can directly coordinate activity in mPFC and hippocampus. Cells with collaterals in the hippocampus–reuniens–mPFC network may be important for the systems consolidation of memory traces and for theta synchronization during exploratory behavior. PMID:23571778

  5. Relationship of angiogenesis and microglial activation to seizure-induced neuronal death in the cerebral cortex of Shetland Sheepdogs with familial epilepsy.

    Science.gov (United States)

    Sakurai, Masashi; Morita, Takehito; Takeuchi, Takashi; Shimada, Akinori

    2013-05-01

    To determine whether angiogenesis and microglial activation were related to seizure-induced neuronal death in the cerebral cortex of Shetland Sheepdogs with familial epilepsy. Cadavers of 10 Shetland Sheepdogs from the same family (6 dogs with seizures and 4 dogs without seizures) and 4 age-matched unrelated Shetland Sheepdogs. Samples of brain tissues were collected after euthanasia and then fixed in neutral phosphate-buffered 10% formalin and routinely embedded in paraffin. The fixed samples were sectioned for H&E staining and immunohistochemical analysis. Evidence of seizure-induced neuronal death was detected exclusively in samples of cerebral cortical tissue from the dogs with familial epilepsy in which seizures had been observed. The seizure-induced neuronal death was restricted to tissues from the cingulate cortex and sulci surrounding the cerebral cortex. In almost the same locations as where seizure-induced neuronal death was identified, microvessels appeared longer and more tortuous and the number of microvessels was greater than in the dogs without seizures and control dogs. Occasionally, the microvessels were surrounded by oval to flat cells, which had positive immunohistochemical results for von Willebrand factor. Immunohistochemical results for neurons and glial cells (astrocytes and microglia) were positive for vascular endothelial growth factor, and microglia positive for ionized calcium-binding adapter molecule 1 were activated (ie, had swollen cell bodies and long processes) in almost all the same locations as where seizure-induced neuronal death was detected. Double-label immunofluorescence techniques revealed that the activated microglia had positive results for tumor necrosis factor-α, interleukin-6, and vascular endothelial growth factor receptor 1. These findings were not observed in the cerebrum of dogs without seizures, whether the dogs were from the same family as those with epilepsy or were unrelated to them. Signs of angiogenesis and

  6. Thalamic hemorrhage in a 4-year-old child induced by nephro-vascular hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Bianchi, E.; Savasta, S.; Torcetta, F.; Solmi, M.; Beluffi, G.; Gajno, T.M.

    1989-08-01

    A child affected by cardiomyopathy from the age of 12 months suddenly manifested right hemiparesis and dysarthria at the age of 48/12 years. Emergency brain CT showed a hemorrhage in progress in the left thalamic area. A serve from of hypertension was concomitant and resisted all pharmacological treatment. Retrograde transfemural aortography pointed out an atrophy of the right renal artery. This finding, together with the high renin and aldosterone values, indicated a nephrogenic hypertension causing both the cardiomyopathy found at 12 months of age and the endocranial hermorrhage. Right nephrectomy led to the normalization of blood pressure. (orig.).

  7. Combined thalamic and subthalamic deep brain stimulation for tremor-dominant Parkinson's disease.

    Science.gov (United States)

    Oertel, Markus F; Schüpbach, W Michael M; Ghika, Joseph-André; Stieglitz, Lennart H; Fiechter, Michael; Kaelin-Lang, Alain; Raabe, Andreas; Pollo, Claudio

    2017-02-01

    Deep brain stimulation (DBS) in the thalamic ventral intermediate (Vim) or the subthalamic nucleus (STN) reportedly improves medication-refractory Parkinson's disease (PD) tremor. However, little is known about the potential synergic effects of combined Vim and STN DBS. We describe a 79-year-old man with medication-refractory tremor-dominant PD. Bilateral Vim DBS electrode implantation produced insufficient improvement. Therefore, the patient underwent additional unilateral left-sided STN DBS. Whereas Vim or STN stimulation alone led to partial improvement, persisting tremor resolution occurred after simultaneous stimulation. The combination of both targets may have a synergic effect and is an alternative option in suitable cases.

  8. REM sleep deprivation induces changes of down regulatory antagonist modulator (DREAM) expression in the ventrobasal thalamic nuclei of sprague-dawley rats.

    Science.gov (United States)

    Siran, Rosfaiizah; Ahmad, Asma Hayati; Abdul Aziz, Che Badariah; Ismail, Zalina

    2014-12-01

    REM sleep is a crucial component of sleep. Animal studies indicate that rapid eye movement (REM) sleep deprivation elicits changes in gene expression. Down regulatory antagonist modulator (DREAM) is a protein which downregulates other gene transcriptions by binding to the downstream response element site. The aim of this study is to examine the effect of REM sleep deprivation on DREAM expression in ventrobasal thalamic nuclei (VB) of rats. Seventy-two male Sprague-Dawley rats were divided into four major groups consisting of free-moving control rats (FMC) (n = 18), 72-h REM sleep-deprived rats (REMsd) (n = 18), 72-h REM sleep-deprived rats with 72-h sleep recovery (RG) (n = 18), and tank control rats (TC) (n = 18). REM sleep deprivation was elicited using the inverted flower pot technique. DREAM expression was examined in VB by immunohistochemical, Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR) studies. The DREAM-positive neuronal cells (DPN) were decreased bilaterally in the VB of rats deprived of REM sleep as well as after sleep recovery. The nuclear DREAM extractions were increased bilaterally in animals deprived of REM sleep. The DREAM messenger RNA (mRNA) levels were decreased after sleep recovery. The results demonstrated a link between DREAM expression and REM sleep deprivation as well as sleep recovery which may indicate potential involvement of DREAM in REM sleep-induced changes in gene expression, specifically in nociceptive processing.

  9. Thalamic abnormalities in children with continuous spike-wave during slow-wave sleep: An F-18-fluorodeoxyglucose positron emission tomography perspective.

    Science.gov (United States)

    Agarwal, Rajkumar; Kumar, Ajay; Tiwari, Vijay N; Chugani, Harry

    2016-02-01

    Thalamic injury has been implicated in the development of continuous spike-wave during slow-wave sleep (CSWS) in children with epilepsy. We studied thalamic abnormalities in children with CSWS using F-18-fluorodeoxyglucose (FDG)-positron emission tomography (PET) imaging. Twenty-three patients (12 male; mean age 9 years) with CSWS and normal thalami on brain magnetic resonance imaging (MRI) underwent FDG-PET. Thalamic glucose metabolism, represented by standardized uptake value normalized to whole brain (nSUV, RT for right thalamus and LT for left thalamus), and its asymmetry--absolute asymmetry index (AAI): ¦(RT-LT)¦*100/[(RT+LT)/2]--was calculated. These values were compared with those from 10 normal healthy controls (five female; mean age 11.1 years). Thalamic glucose metabolism was abnormal in 18 patients (78.3%). Thalamic nSUV was decreased (n = 6) or increased (n = 1) bilaterally in seven children without any asymmetry. Abnormal thalamic symmetry [AAI = 3.7-31.5% (0.8-3.3% in controls)] was seen in 11 children. Of these, six children had a unilateral thalamic metabolic abnormality (increased metabolism, n = 3 and decreased metabolism, n = 3), whereas 5 of 14 children had abnormal asymmetry index with bilaterally normal (n = 4) or increased (n = 1) thalamic metabolism. No clear association of thalamic metabolic abnormalities was seen with the stage of evolution of CSWS (prodromal, acute, or residual) or with the cortical FDG abnormalities. Functional thalamic abnormalities, both unilateral and bilateral, are frequently seen in patients with CSWS. FDG-PET is a sensitive and quantifiable modality to detect these changes. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

  10. Noisy Neurons

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 20; Issue 1. Noisy Neurons: Hodgkin-Huxley Model and Stochastic Variants. Shurti Paranjape. General Article Volume 20 Issue 1 January 2015 pp 34-43. Fulltext. Click here to view fulltext PDF. Permanent link:

  11. Tcf7l2 plays crucial roles in forebrain development through regulation of thalamic and habenular neuron identity and connectivity

    NARCIS (Netherlands)

    Lee, Myungsin; Yoon, Jiyeon; Song, Hobeom; Lee, Bumwhee; Lam, Duc Tri; Yoon, Jaeseung; Baek, Kwanghee; Clevers, Hans; Jeong, Yongsu

    2017-01-01

    The thalamus acts as a central integrator for processing and relaying sensory and motor information to and from the cerebral cortex, and the habenula plays pivotal roles in emotive decision making by modulating dopaminergic and serotonergic circuits. These neural compartments are derived from a

  12. [Diversity in thalamic relay neurons: evidence for "bottom-up" and "top-down" information flow in thalamocortical pathways].

    Science.gov (United States)

    Clascá, Francisco; Rubio-Garrido, Pablo; Galazo, María J; Porrero, César

    2009-01-01

    Thalamocortical (TC) pathways are still mainly understood as the gateway for ascending sensory-motor information into the cortex. However, it is now clear that a great many TC cells are involved in interactions between cortical areas via the thalamus. We review recent data, including our own, which demonstrate the generalized presence in rodent thalamus of two major TC cell types characterized, among other features, by their axon development, arborization and laminar targeting in the cortex. Such duality may allow inputs from thalamus to access cortical circuits via "bottom-up"-wired axon arbors or via "top-down"-wired axon arbors.

  13. Thalamic volume deficit contributes to procedural and explicit memory impairment in HIV infection with primary alcoholism comorbidity.

    Science.gov (United States)

    Fama, Rosemary; Rosenbloom, Margaret J; Sassoon, Stephanie A; Rohlfing, Torsten; Pfefferbaum, Adolf; Sullivan, Edith V

    2014-12-01

    Component cognitive and motor processes contributing to diminished visuomotor procedural learning in HIV infection with comorbid chronic alcoholism (HIV+ALC) include problems with attention and explicit memory processes. The neural correlates associated with this constellation of cognitive and motor processes in HIV infection and alcoholism have yet to be delineated. Frontostriatal regions are affected in HIV infection, frontothalamocerebellar regions are affected in chronic alcoholism, and frontolimbic regions are likely affected in both; all three of these systems have the potential of contributing to both visuomotor procedural learning and explicit memory processes. Here, we examined the neural correlates of implicit memory, explicit memory, attention, and motor tests in 26 HIV+ALC (5 with comorbidity for nonalcohol drug abuse/dependence) and 19 age-range matched healthy control men. Parcellated brain volumes, including cortical, subcortical, and allocortical regions, as well as cortical sulci and ventricles, were derived using the SRI24 brain atlas. Results indicated that smaller thalamic volumes were associated with poorer performance on tests of explicit (immediate and delayed) and implicit (visuomotor procedural) memory in HIV+ALC. By contrast, smaller hippocampal volumes were associated with lower scores on explicit, but not implicit memory. Multiple regression analyses revealed that volumes of both the thalamus and the hippocampus were each unique independent predictors of explicit memory scores. This study provides evidence of a dissociation between implicit and explicit memory tasks in HIV+ALC, with selective relationships observed between hippocampal volume and explicit but not implicit memory, and highlights the relevance of the thalamus to mnemonic processes.

  14. Central thalamic deep brain stimulation for support of forebrain arousal regulation in the minimally conscious state.

    Science.gov (United States)

    Schiff, Nicholas D

    2013-01-01

    This chapter considers the use of central thalamic deep brain stimulation (CT/DBS) to support arousal regulation mechanisms in the minimally conscious state (MCS). CT/DBS for selected patients in a MCS is first placed in the historical context of prior efforts to use thalamic electrical brain stimulation to treat the unconscious clinical conditions of coma and vegetative state. These previous studies and a proof of concept result from a single-subject study of a patient in a MCS are reviewed against the background of new population data providing benchmarks of the natural history of vegetative and MCSs. The conceptual foundations for CT/DBS in selected patients in a MCS are then presented with consideration of both circuit and cellular mechanisms underlying recovery of consciousness identified from empirical studies. Directions for developing future generalizable criteria for CT/DBS that focus on the integrity of necessary brain systems and behavioral profiles in patients in a MCS that may optimally response to support of arousal regulation mechanisms are proposed. © 2013 Elsevier B.V. All rights reserved.

  15. Reduced heat pain thresholds after sad-mood induction are associated with changes in thalamic activity.

    Science.gov (United States)

    Wagner, Gerd; Koschke, Mandy; Leuf, Tanja; Schlösser, Ralf; Bär, Karl-Jürgen

    2009-03-01

    Negative affective states influence pain processing in healthy subjects in terms of augmented pain experience. Furthermore, our previous studies revealed that patients with major depressive disorder showed increased heat pain thresholds on the skin. Potential neurofunctional correlates of this finding were located within the fronto-thalamic network. The aim of the present study was to investigate the neurofunctional underpinnings of the influence of sad mood upon heat pain processing in healthy subjects. For this purpose, we used a combination of the Velten Mood Induction procedure and a piece of music to induce sad affect. Initially we assessed heat pain threshold after successful induction of sad mood outside the MR scanner in Experiment 1. We found a highly significant reduction in heat pain threshold on the left hand and a trend for the right. In Experiment 2, we applied thermal pain stimuli on the left hand (37, 42, and 45 degrees C) in an MRI scanner. Subjects were scanned twice, one group before and after sad-mood induction and another group before and after neutral-mood induction, respectively. Our main finding was a significant group x mood-induction interaction bilaterally in the ventrolateral nucleus of the thalamus indicating a BOLD signal increase after sad-mood induction and a BOLD signal decrease in the control group. We present evidence that induced sad affect leads to reduced heat pain thresholds in healthy subjects. This is probably due to altered lateral thalamic activity, which is potentially associated with changed attentional processes.

  16. Anterior Thalamic High Frequency Band Activity Is Coupled with Theta Oscillations at Rest

    Directory of Open Access Journals (Sweden)

    Catherine M. Sweeney-Reed

    2017-07-01

    Full Text Available Cross-frequency coupling (CFC between slow and fast brain rhythms, in the form of phase–amplitude coupling (PAC, is proposed to enable the coordination of neural oscillatory activity required for cognitive processing. PAC has been identified in the neocortex and mesial temporal regions, varying according to the cognitive task being performed and also at rest. PAC has also been observed in the anterior thalamic nucleus (ATN during memory processing. The thalamus is active during the resting state and has been proposed to be involved in switching between task-free cognitive states such as rest, in which attention is internally-focused, and externally-focused cognitive states, in which an individual engages with environmental stimuli. It is unknown whether PAC is an ongoing phenomenon during the resting state in the ATN, which is modulated during different cognitive states, or whether it only arises during the performance of specific tasks. We analyzed electrophysiological recordings of ATN activity during rest from seven patients who received thalamic electrodes implanted for treatment of pharmacoresistant focal epilepsy. PAC was identified between theta (4–6 Hz phase and high frequency band (80–150 Hz amplitude during rest in all seven patients, which diminished during engagement in tasks involving an external focus of attention. The findings are consistent with the proposal that theta–gamma coupling in the ATN is an ongoing phenomenon, which is modulated by task performance.

  17. Case of herpes simplex encephalitis(HSE) with a thalamic lesion

    Energy Technology Data Exchange (ETDEWEB)

    Fujimori, K.; Koike, R.; Yuasa, T.; Miyatake, T.; Ito, J.

    1987-02-01

    A case of herpes simplex encephalitis (HSE) with thalamic involvement was reported. The patient, a 27-year-old man, was admitted because of abnormal behavior and fever. He exhibited a disturbance of consciousness, meningial signs, and hyperreflexia. A CT scan of the head revealed diffuse brain edema. Acute encephalitis, especially HSE, was suspected, and so the intravenous administration of acyclovir and steroid therapy were started. The titer of herpes simplex Type 1 virus, as measured by CF and ELISA, was found to have increased amounts of serum and cerebrospinal fluid. 5 days after the onset, his consciousness worsened. He could not tell his name and scarely opened his eyes upon pain stimulation. A CT scan at this time showed low-density lesions in the left thalamus, cingulate gyrus, and the posterior portion of the putamen. About 5 days later, his consciousness level was increased, but he was mute. This symptom was thought to be thalamic aphasia, which might be correlative with the low-density lesions shown in the left thalamus by the CT scan. About 30 days after the onset of the disease, his speech became normal, and a CT scan at 51 hospital days showed no abnormality. The etiology of low-density lesions of the left thalamus in the CT scan is speculated to be as follows: firstly, vascular damage of circulation disturbance, and secondly a special affinity of herpes simplex Type 1 virus to the thalamus.

  18. Contributions of the Paraventricular Thalamic Nucleus in the Regulation of Stress, Motivation, and Mood

    Directory of Open Access Journals (Sweden)

    David Tai Hsu

    2014-03-01

    Full Text Available The purpose of this review is to describe how the function and connections of the paraventricular thalamic nucleus (Pa may play a role in the regulation of stress and negative emotional behavior. Located in the dorsal midline thalamus, the Pa is heavily innervated by serotonin, norepinephrine, dopamine, corticotropin-releasing hormone, and orexins, and is the only thalamic nucleus connected to the group of structures comprising the amygdala, bed nucleus of the stria terminalis, nucleus accumbens, and infralimbic/subgenual anterior cingulate cortex. These neurotransmitter systems and structures are involved in regulating motivation and mood, and display abnormal functioning in several psychiatric disorders including anxiety, substance use, and major depressive disorders. Furthermore, rodent studies show that the Pa is consistently and potently activated following a variety of stressors and has a unique role in regulating responses to chronic stressors. These observations provide a compelling rationale for investigating the Pa in the link between stress and negative emotional behavior, and for including the Pa in the neural pathways of stress-related psychiatric disorders.

  19. The emotional tunes and the role of mirror neurons: From primary relationship mother-child relation to rehabilitation and therapeutic music therapy

    Directory of Open Access Journals (Sweden)

    Stefania La Porta

    2016-05-01

    His research has been forming the basis of the theoretical and methodological focus of music therapy to psychodynamic. The ability to reproduce the relational process characterized by affective attunements in a rehabilitation setting - music therapy where there are dis-evolution, as in the case of patients with Alzheimer's disease, you can reactivate capacity affective and relational residual strengthening in the subject 'personal and social identity mortified by the disease. Role within that path is done by a very peculiar type of neurons, mirror neurons, the subject of study in recent years by the neurosciences, whose characteristic would be to get excited is when a person performs a certain action, both when it is another to do it before his eyes.

  20. Effects of Hallucinogens on Neuronal Activity.

    Science.gov (United States)

    Lladó-Pelfort, L; Celada, P; Riga, M S; Troyano-Rodríguez, E; Santana, N; Artigas, F

    2017-02-26

    Hallucinogens evoke sensory, perceptual, affective, and cognitive effects that may be useful to understand the neurobiological basis of mood and psychotic disorders. The present chapter reviews preclinical research carried out in recent years in order to better understand the action of psychotomimetic agents such as the noncompetitive NMDA receptor (NMDA-R) antagonists and serotonergic hallucinogens. Our studies have focused on the mechanisms through which these agents alter cortical activity. Noncompetitive NMDA-R antagonists, such as phencyclidine (PCP) and MK-801 (dizocilpine), as well as the serotonergic hallucinogens DOI and 5-MeO-DMT, produce similar effects on cellular and population activity in prefrontal cortex (PFC); these effects include alterations of pyramidal neuron discharge (with an overall increase in firing), as well as a marked attenuation of the low frequency oscillations (0.2-4 Hz) to which neuronal discharge is coupled in anesthetized rodents. PCP increases c-fos expression in excitatory neurons from various cortical and subcortical areas, particularly the thalamus. This effect of PCP involves the preferential blockade of NMDA-R on GABAergic neurons of the reticular nucleus of the thalamus, which provides feedforward inhibition to the rest of thalamic nuclei. It is still unknown whether serotonergic hallucinogens also affect thalamocortical networks. However, when examined, similar alterations in other cortical areas, such as the primary visual cortex (V1), have been observed, suggesting that these agents affect cortical activity in sensory and associative areas. Interestingly, the disruption of PFC activity induced by PCP, DOI and 5-MeO-DMT is reversed by classical and atypical antipsychotic drugs. This effect suggests a possible link between the mechanisms underlying the disruption of perception by multiple classes of hallucinogenic agents and the therapeutic efficacy of antipsychotic agents.

  1. A relationship between reduced nucleus accumbens shell and enhanced lateral hypothalamic orexin neuronal activation in long-term fructose bingeing behavior.

    Directory of Open Access Journals (Sweden)

    Jacki M Rorabaugh

    Full Text Available Fructose accounts for 10% of daily calories in the American diet. Fructose, but not glucose, given intracerebroventricularly stimulates homeostatic feeding mechanisms within the hypothalamus; however, little is known about how fructose affects hedonic feeding centers. Repeated ingestion of sucrose, a disaccharide of fructose and glucose, increases neuronal activity in hedonic centers, the nucleus accumbens (NAc shell and core, but not the hypothalamus. Rats given glucose in the intermittent access model (IAM display signatures of hedonic feeding including bingeing and altered DA receptor (R numbers within the NAc. Here we examined whether substituting fructose for glucose in this IAM produces bingeing behavior, alters DA Rs and activates hedonic and homeostatic feeding centers. Following long-term (21-day exposure to the IAM, rats given 8-12% fructose solutions displayed fructose bingeing but unaltered DA D1R or D2R number. Fructose bingeing rats, as compared to chow bingeing controls, exhibited reduced NAc shell neuron activation, as determined by c-Fos-immunoreactivity (Fos-IR. This activation was negatively correlated with orexin (Orx neuron activation in the lateral hypothalamus/perifornical area (LH/PeF, a brain region linking homeostatic to hedonic feeding centers. Following short-term (2-day access to the IAM, rats exhibited bingeing but unchanged Fos-IR, suggesting only long-term fructose bingeing increases Orx release. In long-term fructose bingeing rats, pretreatment with the Ox1R antagonist SB-334867 (30 mg/kg; i.p. equally reduced fructose bingeing and chow intake, resulting in a 50% reduction in calories. Similarly, in control rats, SB-334867 reduced chow/caloric intake by 60%. Thus, in the IAM, Ox1Rs appear to regulate feeding based on caloric content rather than palatability. Overall, our results, in combination with the literature, suggest individual monosaccharides activate distinct neuronal circuits to promote feeding behavior

  2. Recall deficits in stroke patients with thalamic lesions covary with damage to the parvocellular mediodorsal nucleus of the thalamus.

    Science.gov (United States)

    Pergola, Giulio; Güntürkün, Onur; Koch, Benno; Schwarz, Michael; Daum, Irene; Suchan, Boris

    2012-08-01

    The functional role of the mediodorsal thalamic nucleus (MD) and its cortical network in memory processes is discussed controversially. While Aggleton and Brown (1999) suggested a role for recognition and not recall, Van der Werf et al. (2003) suggested that this nucleus is functionally related to executive function and strategic retrieval, based on its connections to the prefrontal cortices (PFC). The present study used a lesion approach including patients with focal thalamic lesions to examine the functions of the MD, the intralaminar nuclei and the midline nuclei in memory processing. A newly designed pair association task was used, which allowed the assessment of recognition and cued recall performance. Volume loss in thalamic nuclei was estimated as a predictor for alterations in memory performance. Patients performed poorer than healthy controls on recognition accuracy and cued recall. Furthermore, patients responded slower than controls specifically on recognition trials followed by successful cued recall of the paired associate. Reduced recall of picture pairs and increased response times during recognition followed by cued recall covaried with the volume loss in the parvocellular MD. This pattern suggests a role of this thalamic region in recall and thus recollection, which does not fit the framework proposed by Aggleton and Brown (1999). The functional specialization of the parvocellular MD accords with its connectivity to the dorsolateral PFC, highlighting the role of this thalamocortical network in explicit memory (Van der Werf et al., 2003). Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Functional characterization and expression of thalamic GABAB receptors in a rodent model of Parkinson’s disease

    NARCIS (Netherlands)

    Groote, C. de; Wüllner, U.; Löschmann, P.-A.; Luiten, P.G.M.; Klockgether, T.

    1999-01-01

    Increased GABAergic neurotransmission of the basal ganglia output nuclei projecting to the motor thalamus is thought to contribute to the pathophysiology of Parkinson’s disease. We investigated the functional role of thalamic GABAB receptors in a rodent model of Parkinson’s disease. First, we

  4. Functional characterization and expression of thalamic GABA(B) receptors in a rodent model of Parkinson's disease

    NARCIS (Netherlands)

    de Groote, C; Wullner, U; Loschmann, PA; Luiten, PGM; Klockgether, T

    1999-01-01

    Increased GABAergic neurotransmission of the basal ganglia output nuclei projecting to the motor thalamus is thought to contribute to the pathophysiology of Parkinson's disease. We investigated the functional role of thalamic GABA(B) receptors in a rodent model of Parkinson's disease. First, we

  5. Effective connectivity of ascending and descending frontal-thalamic pathways during sustained attention: Complex brain network interactions in adolescence

    Science.gov (United States)

    Jagtap, Pranav; Diwadkar, Vaibhav A.

    2016-01-01

    Frontal-thalamic interactions are crucial for bottom-up gating and top-down control, yet have not been well studied from brain network perspectives. We applied network modeling of fMRI signals (Dynamic Causal Modeling; DCM) to investigate frontal-thalamic interactions during an attention task with parametrically varying levels of demand. fMRI was collected while subjects participated in a sustained continuous performance task with low and high attention demands. 162 competing model architectures were employed in DCM to evaluate hypotheses on bilateral frontal-thalamic connections and their modulation by attention demand, selected at a second level using Bayesian Model Selection. The model architecture evinced significant contextual modulation by attention of ascending (thalamus → dPFC) and descending (dPFC → thalamus) pathways. However, modulation of these pathways was asymmetric: While positive modulation of the ascending pathway was comparable across attention demand, modulation of the descending pathway was significantly greater when attention demands were increased. Increased modulation of the (dPFC → thalamus) pathway in response to increased attention demand constitutes novel evidence of attention-related gain in the connectivity of the descending attention pathway. By comparison demand-independent modulation of the ascending (thalamus → dPFC) pathway suggests unbiased thalamic inputs to the cortex in the context of the paradigm. PMID:27145923

  6. Thalamic glucose metabolism in temporal lobe epilepsy measured with 18F-FDG positron emission tomography (PET)

    NARCIS (Netherlands)

    Khan, N; Leenders, KL; Hajek, M; Maguire, P; Missimer, J; Wieser, HG

    1997-01-01

    Thalamic glucose metabolism has been studied in 24 patients suffering from temporal lobe epilepsy (TLE) using interictal F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET). A total of 17 patients had a unilateral TL seizure onset, 11 of these patients had a mesial temporal lobe

  7. Measuring the signal-to-noise ratio of a neuron.

    Science.gov (United States)

    Czanner, Gabriela; Sarma, Sridevi V; Ba, Demba; Eden, Uri T; Wu, Wei; Eskandar, Emad; Lim, Hubert H; Temereanca, Simona; Suzuki, Wendy A; Brown, Emery N

    2015-06-09

    The signal-to-noise ratio (SNR), a commonly used measure of fidelity in physical systems, is defined as the ratio of the squared amplitude or variance of a signal relative to the variance of the noise. This definition is not appropriate for neural systems in which spiking activity is more accurately represented as point processes. We show that the SNR estimates a ratio of expected prediction errors and extend the standard definition to one appropriate for single neurons by representing neural spiking activity using point process generalized linear models (PP-GLM). We estimate the prediction errors using the residual deviances from the PP-GLM fits. Because the deviance is an approximate χ(2) random variable, we compute a bias-corrected SNR estimate appropriate for single-neuron analysis and use the bootstrap to assess its uncertainty. In the analyses of four systems neuroscience experiments, we show that the SNRs are -10 dB to -3 dB for guinea pig auditory cortex neurons, -18 dB to -7 dB for rat thalamic neurons, -28 dB to -14 dB for monkey hippocampal neurons, and -29 dB to -20 dB for human subthalamic neurons. The new SNR definition makes explicit in the measure commonly used for physical systems the often-quoted observation that single neurons have low SNRs. The neuron's spiking history is frequently a more informative covariate for predicting spiking propensity than the applied stimulus. Our new SNR definition extends to any GLM system in which the factors modulating the response can be expressed as separate components of a likelihood function.

  8. Crossed cerebellar diaschisis in acute isolated thalamic infarction detected by dynamic susceptibility contrast perfusion MRI.

    Directory of Open Access Journals (Sweden)

    Alex Förster

    Full Text Available PURPOSE: Crossed cerebellar diaschisis (CCD is a state of neural depression caused by loss of connections to injured neural structures remote from the cerebellum usually evaluated by positron emission tomography. Recently it has been shown that dynamic susceptibility contrast perfusion weighted MRI (PWI may also be feasible to detect the phenomenon. In this study we aimed to assess the frequency of CCD on PWI in patients with acute thalamic infarction. METHODS: From a MRI report database we identified patients with acute isolated thalamic infarction. Contralateral cerebellar hypoperfusion was identified by inspection of time to peak (TTP maps and evaluated quantitatively on TTP, mean transit time (MTT, cerebral blood flow and volume (CBF, CBV maps. A competing cerebellar pathology or an underlying vascular pathology were excluded. RESULTS: A total of 39 patients was included. Common symptoms were hemiparesis (53.8%, hemihypaesthesia (38.5%, dysarthria (30.8%, aphasia (17.9%, and ataxia (15.4%. In 9 patients (23.1% PWI showed hypoperfusion in the contralateral cerebellar hemisphere. All of these had lesions in the territory of the tuberothalamic, paramedian, or inferolateral arteries. Dysarthria was observed more frequently in patients with CCD (6/9 vs. 6/30; OR 8.00; 95%CI 1.54-41.64, p = 0.01. In patients with CCD, the median ischemic lesion volume on DWI (0.91 cm³, IQR 0.49-1.54 cm³ was larger compared to patients with unremarkable PWI (0.51 cm³, IQR 0.32-0.74, p = 0.05. The most pronounced changes were found in CBF (0.94±0.11 and MTT (1.06±0.13 signal ratios, followed by TTP (1.05±0.02. CONCLUSIONS: Multimodal MRI demonstrates CCD in about 20% of acute isolated thalamic infarction patients. Lesion size seems to be a relevant factor in its pathophysiology.

  9. Altered cortico-striatal-thalamic connectivity in relation to spatial working memory capacity in children with ADHD

    Directory of Open Access Journals (Sweden)

    Kathryn L. Mills

    2012-01-01

    Full Text Available Introduction: Attention deficit hyperactivity disorder (ADHD captures a heterogeneous group of children, who are characterized by a range of cognitive and behavioral symptoms. Previous resting state functional connectivity (rs-fcMRI studies have sought to understand the neural correlates of ADHD by comparing connectivity measurements between those with and without the disorder, focusing primarily on cortical-striatal circuits mediated by the thalamus. To integrate the multiple phenotypic features associated with ADHD and help resolve its heterogeneity, it is helpful to determine how specific circuits relate to unique cognitive domains of the ADHD syndrome. Spatial working memory has been proposed as a key mechanism in the pathophysiology of ADHD.Methods: We correlated the rs-fcMRI of five thalamic regions of interest with spatial span working memory scores in a sample of 67 children aged 7-11 years (ADHD and typically developing children; TDC. In an independent dataset, we then examined group differences in thalamo-striatal functional connectivity between 70 ADHD and 89 TDC (7-11 years from the ADHD-200 dataset. Thalamic regions of interest were created based on previous methods that utilize known thalamo-cortical loops and rs-fcMRI to identify functional boundaries in the thalamus.Results/Conclusions: Using these thalamic regions, we found atypical rs-fcMRI between specific thalamic groupings with the basal ganglia. To identify the thalamic connections that relate to spatial working memory in ADHD, only connections identified in both the correlational and comparative analyses were considered. Multiple connections between the thalamus and basal ganglia, particularly between medial and anterior dorsal thalamus and the putamen, were related to spatial working memory and also altered in ADHD. These thalamo-striatal disruptions may be one of multiple atypical neural and cognitive mechanisms that relate to the ADHD clinical phenotype.

  10. The findings of Tc-99m ECD brain perfusion SPECT in the patients with left anterior thalamic infarction

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Y. A.; Kim, S. H.; Sohn, H. S.; Jeong, S. G. [The Catholic University of Korea, Seoul (Korea, Republic of)

    2005-07-01

    The thalamus has multiple connections with areas of the cerebral cortex involved in arousal and cognition. Thalamic damage has been reported to be associated with variable neuropsychological dysfunctions and dementia. This study evaluates the changes of regional cerebral blood flow (rCBF) by using SPM analysis of brain perfusion SPECT and examining the neuropsychological abnormalities of 4 patients with anterior thalamic infarctions. Four patients with left anterior thalamic infarctions and eleven normal controls were evaluated. K-MMSE and the Seoul Neuropsychological Screening Battery were performed within 2 days after stroke. The normalized SPECT data of 4 patients were compared to those of 11 controls for the detection of areas with decreased rCBF by SPM analysis. All 4 patients showed anterograde amnesia in their verbal memory, which was not improved by recognition. Dysexecutive features were occasionally present, such as decreased word fluency and impaired Stroop test results. SPM analysis revealed decreased rCBF in the left supra marginal gyrus, the superior temporal gyrus, the middle and inferior frontal gyrus, the medial dorsal and anterior nucleus of the left thalamus. The changes of rCBF in patients with left anterior thalamic infarctions may be due to the remote suppression on metabolism by the interruption of the cortico-subcortical circuit, which connects the anterior thalamic nucleus and various cortical areas. The executive dysfunction and dysnomia may be caused by the left dorsolateral frontal dysfunction of the thalamo-cortical circuit. Anterograde amnesia with storage deficit may be caused by the disruption of mamillothalamic tract.

  11. [Persistent psychotic disorder following bilateral mesencephalo-thalamic ischaemia: case report].

    Science.gov (United States)

    Predescu, A; Damsa, C; Riegert, M; Bumb, A; Pull, C

    2004-01-01

    A 38-year old male patient with no history of psychiatric illness developed a progressive psychotic disorder after bilateral (predominantly left) mesencephalo-thalamic cerebral ischaemia. The reason of the emergency hospitalization was the sudden onset of a confusional state, culminating in a fluctuating comatose status. The neurological examination found mild right hemiparesia, praxic disorders and reactive left mydriasis with paresia of the downward vertical stare, leading to the hospitalisation in the neurology department for suspicion of a cerebral vascular ischaemic accident. The psychiatric symptoms started with acoustic-verbal hallucinations, poorly structured paranoid delusions, progressively developed over two weeks, followed by behavioural disorders with psychomotor agitation and heteroaggressivity. The patient was transferred to the psychiatric department, because of the heteroaggressive risk and lack of morbid consciousness, in spite of recovering from the confusional status. An intensive psychiatric management was proposed, combining a psychotherapeutic approach with 4 mg of risperidone and adjustable doses of benzodiazepine according to the psychomotor agitation. During the next days, there was a net recovery of the behavioural disorders, in spite of the persistence of the ideas of persecution. All the neurological symptoms also decreased. An anomaly of the polygon of Willis was found on a cerebral arteriography (the posterior cerebral arteries had a foetal origin, dependent on carotidal axes and not on the vertebro-basilar system). The main emboligen risk factor was the presence of a permeable foramen ovale, discovered during a transoesophageal echography. The patient underwent a surgical correction of the permeable foramen ovale. The psychiatric hospitalization for three months was continued by ambulatory follow-up. The initial positive symptoms (delusions, acoustic-verbal hallucinations) progressively diminished while negative symptoms became

  12. Bilateral thalamic stimulation induces insomnia in patients treated for intractable tremor.

    Science.gov (United States)

    Bridoux, Agathe; Drouot, Xavier; Sangare, Aude; Al-Ani, Tarik; Brignol, Arnaud; Charles-Nelson, Anais; Brugières, Pierre; Gouello, Gaëtane; Hosomi, Koichi; Lepetit, Hélène; Palfi, Stéphane

    2015-03-01

    To explore the influence of acute bilateral ventral intermediate thalamic nucleus (VIM) stimulation on sleep. Three consecutive full-night polysomnography recordings were made in the laboratory. After the habituation night, a random order for night ON-stim and OFF-stim was applied for the second and third nights. Sleep disorders unit of a university hospital. Eleven patients with bilateral stimulation of the ventral intermediate nucleus of the thalamus (VIM) for drug-resistant tremor. Sleep measures on polysomnography. Total sleep time was reduced during night ON-stim compared to OFF- stim, as well as rapid eye movement sleep percentage while the percentage of N2 increased. Wakefulness after sleep onset time was increased. Our results show that bilateral stimulation of the VIM nuclei reduces sleep and could be associated with insomnia. © 2015 Associated Professional Sleep Societies, LLC.

  13. Bilateral symmetrical basal ganglia and thalamic lesions in children: an update (2015)

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    Zuccoli, Giulio [Children' s Hospital of Pittsburgh of UPMC, Section of Neuroradiology, Pittsburgh, PA (United States); Yannes, Michael Paul [University of Pittsburgh School of Medicine, Department of Radiology, Pittsburgh, PA (United States); Nardone, Raffaele [Paracelsus Medical University, Department of Neurology, Christian Doppler Klinik, Salzburg (Austria); Bailey, Ariel [West Virginia University, Department of Radiology, Morgantown, WV (United States); Goldstein, Amy [Children' s Hospital of Pittsburgh of UPMC, Department of Neurology, Section of Metabolic Disorders and Neurogenetics, Pittsburgh, PA (United States)

    2015-10-15

    In children, many inherited or acquired neurological disorders may cause bilateral symmetrical signal intensity alterations in the basal ganglia and thalami. A literature review was aimed at assisting neuroradiologists, neurologists, infectious diseases specialists, and pediatricians to provide further understanding into the clinical and neuroimaging features in pediatric patients presenting with bilateral symmetrical basal ganglia and thalamic lesions on magnetic resonance imaging (MRI). We discuss hypoxic-ischemic, toxic, infectious, immune-mediated, mitochondrial, metabolic, and neurodegenerative disorders affecting the basal ganglia and thalami. Recognition and correct evaluation of basal ganglia abnormalities, together with a proper neurological examination and laboratory findings, may enable the identification of each of these clinical entities and lead to earlier diagnosis. (orig.)

  14. Lateralization of observational fear learning at the cortical but not thalamic level in mice.

    Science.gov (United States)

    Kim, Sangwoo; Mátyás, Ferenc; Lee, Sukchan; Acsády, László; Shin, Hee-Sup

    2012-09-18

    Major cognitive and emotional faculties are dominantly lateralized in the human cerebral cortex. The mechanism of this lateralization has remained elusive owing to the inaccessibility of human brains to many experimental manipulations. In this study we demonstrate the hemispheric lateralization of observational fear learning in mice. Using unilateral inactivation as well as electrical stimulation of the anterior cingulate cortex (ACC), we show that observational fear learning is controlled by the right but not the left ACC. In contrast to the cortex, inactivation of either left or right thalamic nuclei, both of which are in reciprocal connection to ACC, induced similar impairment of this behavior. The data suggest that lateralization of negative emotions is an evolutionarily conserved trait and mainly involves cortical operations. Lateralization of the observational fear learning behavior in a rodent model will allow detailed analysis of cortical asymmetry in cognitive functions.

  15. [Thalamic Stroke and Associated Behavior Disorders. Possibilities for Integral Management: Case Report].

    Science.gov (United States)

    Camargo, Loida Camargo; Sánchez, Katherine Parra

    2012-06-01

    Since ancient Greece, cerebrovascular accidents have been described with no variation. Even today, they are still a catastrophic event in the lives of patients with a high risk of disabling sequelae. Case report of a 56-year male patient with thalamic ischemia. The intervention with integral strategies involving pharmacological management and cognitive interventions was decisive for the satisfactory evolution of the patient. The management of patients with cerebrovascular accidents cannot be limited to the emergency room. Pharmacological advances in programs and cognitive intervention methods provide intervention tools from the very beginning of the stroke thus reducing the impact of long-term sequelae, and consequently enabling a better reintegration of the patient to his family. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  16. 3-D tracing of biocytin-labelled pallido-thalamic axons in the monkey.

    Science.gov (United States)

    Arecchi-Bouchhioua, P; Yelnik, J; François, C; Percheron, G; Tandé, D

    1996-04-10

    This study presents three-dimensional tracings of axons and axonal endings of associative pallido-thalamic axons in the monkey (Macaca mulatta, M. irus). Injections of the anterograde tracer biocytin were made in the dorsal, associative region of the medial pallidum. Numerous axonal endings were observed throughout the pallidal territory of the thalamus. Four individual axons were reconstructed from serial sections and traced in three dimensions. The initial branch of each axon subdivided successively, each new branch ending in a different part of the pallidal territory. Each of the latter branches ended in a characteristic, extremely dense terminal arborization, that we called a bunch. Associative medial pallidal information may therefore be distributed throughout the pallidal territory by means of numerous branches and bunches.

  17. INTRINSIC ELECTRICAL PROPERTIES OF MAMMALIAN NEURONS AND CNS FUNCTION: A HISTORICAL PERSPECTIVE

    Directory of Open Access Journals (Sweden)

    Rodolfo R Llinas

    2014-11-01

    Full Text Available This brief review summarizes work done in mammalian neuroscience concerning the intrinsic electrophysiological properties of four neuronal types; Cerebellar Purkinje cells, inferior olivary cells, thalamic cells, and some cortical interneurons. It is a personal perspective addressing an interesting time in neuroscience when the reflex view of brain function, as the paradigm to understand global neuroscience, began to be modified towards one in which sensory input modulates rather than dictates brain function. The perspective of the paper is not a comprehensive description of the intrinsic electrical properties of all nerve cells but rather addresses a set of cell types that provide indicative examples of mechanisms that modulate brain function.

  18. Thalamic metabolic abnormalities in patients with Huntington's disease measured by magnetic resonance spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Casseb, R.F.; Castellano, G., E-mail: gabriela@ifi.unicamp.br [Cooperacao Interinstitucional de Apoio a Pesquisas sobre o Cerebro (Programa CInAPCe), Sao Paulo, SP (Brazil); Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Instituto de Fisica Gleb Wataghin. Dept. de Raios Cosmicos e Cronologia; D' Abreu, A.; Cendes, F. [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Dept. de Neurologia. Lab. de Neuroimagem; Cooperacao Interinstitucional de Apoio a Pesquisas sobre o Cerebro (Programa CInAPCe), Sao Paulo, SP (Brazil); Ruocco, H.H. [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Fac. de Ciencias Medicas. Dept. de Neurologia. Lab. de Neuroimagem; Lopes-Cendes, I., E-mail: seixas.fk@gmail.com [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Fac. de Ciencias Medicas. Dept. de Genetica Medica; Cooperacao Interinstitucional de Apoio a Pesquisas sobre o Cerebro (Programa CInAPCe), Sao Paulo, SP (Brazil)

    2013-08-15

    Huntington's disease (HD) is a neurologic disorder that is not completely understood; its fundamental physiological mechanisms and chemical effects remain somewhat unclear. Among these uncertainties, we can highlight information about the concentrations of brain metabolites, which have been widely discussed. Concentration differences in affected, compared to healthy, individuals could lead to the development of useful tools for evaluating the progression of disease, or to the advance of investigations of different/alternative treatments. The aim of this study was to compare the thalamic concentration of metabolites in HD patients and healthy individuals using magnetic resonance spectroscopy. We used a 2.0-Tesla magnetic field, repetition time of 1500 ms, and echo time of 135 ms. Spectra from 40 adult HD patients and 26 control subjects were compared. Quantitative analysis was performed using the LCModel method. There were statistically significant differences between HD patients and controls in the concentrations of N-acetylaspartate+N-acetylaspartylglutamate (NAA+NAAG; t-test, P,0.001), and glycerophosphocholine+phosphocholine (GPC+PCh; t-test, P=0.001) relative to creatine+phosphocreatine (Cr+PCr). The NAA+NAAG/Cr+PCr ratio was decreased by 9% and GPC+PCh/Cr+PCr increased by 17% in patients compared with controls. There were no correlations between the concentration ratios and clinical features. Although these results could be caused by T1 and T2 changes, rather than variations in metabolite concentrations given the short repetition time and long echo time values used, our findings point to thalamic dysfunction, corroborating prior evidence. (author)

  19. Abnormal medial thalamic metabolism in patients with idiopathic restless legs syndrome.

    Science.gov (United States)

    Rizzo, Giovanni; Tonon, Caterina; Testa, Claudia; Manners, David; Vetrugno, Roberto; Pizza, Fabio; Marconi, Sara; Malucelli, Emil; Provini, Federica; Plazzi, Giuseppe; Montagna, Pasquale; Lodi, Raffaele

    2012-12-01

    Pathophysiology of restless legs syndrome is poorly understood. A role of the thalamus, specifically of its medial portion which is a part of the limbic system, was suggested by functional magnetic resonance imaging and positron emission tomography studies. The aim of this study was to evaluate medial thalamus metabolism and structural integrity in patients with idiopathic restless legs syndrome using a multimodal magnetic resonance approach, including proton magnetic resonance spectroscopy, diffusion tensor imaging, voxel-based morphometry and volumetric and shape analysis. Twenty-three patients and 19 healthy controls were studied in a 1.5 T system. Single voxel proton magnetic resonance spectra were acquired in the medial region of the thalamus. In diffusion tensor examination, mean diffusivity and fractional anisotropy were determined at the level of medial thalamus using regions of interest delineated to outline the same parenchyma studied by spectroscopy. Voxel-based morphometry was performed focusing the analysis on the thalamus. Thalamic volumes were obtained using FMRIB's Integrated Registration and Segmentation Tool software, and shape analysis was performed using the FMRIB Software Library tools. Proton magnetic resonance spectroscopy study disclosed a significantly reduced N-acetylaspartate:creatine ratio and N-acetylaspartate concentrations in the medial thalamus of patients with restless legs syndrome compared with healthy controls (P history of restless legs syndrome (β = -0.49; P = 0.018). On the contrary, diffusion tensor imaging, voxel-based morphometry and volumetric and shape analysis of the thalami did not show differences between the two groups. Proton magnetic resonance spectroscopic findings in patients with restless legs syndrome indicate an involvement of medial thalamic nuclei of a functional nature; however, the other structural techniques of the same region did not show any changes. These findings support the hypothesis

  20. CT classification of small thalamic hemorrhages. Topographic localization and clinical manifestation

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    Kawahara, Nobutaka; Kaneko, Mitsuo; Tanaka, Keisei; Muraki, Masaaki; Sato, Kengo (Hamamatsu Medical Center Hospital, Shizuoka (Japan))

    1984-06-01

    The thalamus is located deep in the cerebral hemispheres, and most of its nuclei have reciprocal fiber connections with specific areas over the cerebral cortex. Localized lesions in the thalamus, therefore, can cause specific neurological deficits, depending on their locations. From this point of view, we reviewed 110 cases, admitted over the past 7 years, with thalamic hemorrhages 37 (34%) of which were small hematomas less than 2 cm in diameter. These small hematomas could be divided into 4 types depending on their locations as follows: antero-lateral type, postero-lateral type, medial type, and dorsal type. Each type had the peculiar clinical features described below: 1) Postero-lateral Type (PL type, 28 cases, 76%): The original symptom was a sudden onset of moderate to severe sensori-motor deficits in most cases. The patients were mostly alert or only slightly confused. 2) Antero-lateral Type (AL type, 4 cases, 11%): The patients of this type first presented with sensori-motor disturbance and prefrontal signs. Both were generally mild and often disappeared early. 3) Medial Type (M type, 3 cases, 8%): The main symptom at onset was either a disturbance of consciousness or dementia. 4) Dorsal Type (D type, 2 cases, 5%): One patient with a right thalamic hematoma of this type showed geographical agnosia and visuo-constructive apraxia. The other patient, with a left-sided hematoma, exhibited transient clumsiness of the right hand and mild dysphasia. In our experience, the above classification of small hematomas clearly delineated the clinical symptoms and neurological signs of the different types; therefore, the symptoms and signs in larger hematoma could be explained by a combination of those of each type.

  1. Strategic lesions in the anterior thalamic radiation and apathy in early Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Mario Torso

    Full Text Available Behavioural disorders and psychological symptoms of Dementia (BPSD are commonly observed in Alzheimer's disease (AD, and strongly contribute to increasing patients' disability. Using voxel-lesion-symptom mapping (VLSM, we investigated the impact of white matter lesions (WMLs on the severity of BPSD in patients with amnestic mild cognitive impairment (a-MCI.Thirty-one a-MCI patients (with a conversion rate to AD of 32% at 2 year follow-up and 26 healthy controls underwent magnetic resonance imaging (MRI examination at 3T, including T2-weighted and fluid-attenuated-inversion-recovery images, and T1-weighted volumes. In the patient group, BPSD was assessed using the Neuropsychiatric Inventory-12. After quantitative definition of WMLs, their distribution was investigated, without an a priori anatomical hypothesis, against patients' behavioural symptoms. Unbiased regional grey matter volumetrics was also used to assess the contribution of grey matter atrophy to BPSD.Apathy, irritability, depression/dysphoria, anxiety and agitation were shown to be the most common symptoms in the patient sample. Despite a more widespread anatomical distribution, a-MCI patients did not differ from controls in WML volumes. VLSM revealed a strict association between the presence of lesions in the anterior thalamic radiations (ATRs and the severity of apathy. Regional grey matter atrophy did not account for any BPSD.This study indicates that damage to the ATRs is strategic for the occurrence of apathy in patients with a-MCI. Disconnection between the prefrontal cortex and the mediodorsal and anterior thalamic nuclei might represent the pathophysiological substrate for apathy, which is one of the most common psychopathological symptoms observed in dementia.

  2. Calcium-binding proteins in the laterodorsal thalamic nucleus during development of the guinea pig.

    Science.gov (United States)

    Zakowski, Witold; Bogus-Nowakowska, Krystyna; Wasilewska, Barbara; Hermanowicz, Beata; Robak, Anna

    2014-11-01

    The laterodorsal thalamic nucleus (LD) is often treated as a part of the anterior thalamic nuclei (ATN) because of its location and similar connectivity. Our previous studies have shown that distribution of three calcium-binding proteins, i.e. calbindin D28k (CB), calretinin (CR) and parvalbumin (PV), changes within the ATN during development of the guinea pig. The aim of this study is to examine the immunoreactivity pattern of these proteins in the LD in the guinea pig ontogeny. Brains from animals ranging from 40th embryonic day to 80th postnatal day were used in the study. Two methods were applied: a single-labelling immunoenzymatic method and double-labelling immunofluorescence. No changes of the distribution pattern of the substances were observed throughout the examined developmental stages. CB and CR were the most abundantly expressed proteins in perikarya of the LD. Numerous CB- and CR-immunoreactive cell bodies were found throughout the whole extent of the nucleus. In most of these cell bodies both proteins colocalized vastly. The highest immunoreactivity of the perikarya containing CB and CR was observed in the mediodorsal part of the LD and in its rostral portion. In regard to PV, single cell bodies were observed mostly in the dorsal part of the nucleus. PV did not colocalize with the other proteins. In summary, all the studied calcium-binding proteins were already present in the LD at prenatal developmental stages and the pattern of distribution remained virtually constant until adulthood. Thus, the LD differs considerably from the ATN in an aspect of neurochemical cell differentiation. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Strategic lesions in the anterior thalamic radiation and apathy in early Alzheimer's disease.

    Science.gov (United States)

    Torso, Mario; Serra, Laura; Giulietti, Giovanni; Spanò, Barbara; Tuzzi, Elisa; Koch, Giacomo; Caltagirone, Carlo; Cercignani, Mara; Bozzali, Marco

    2015-01-01

    Behavioural disorders and psychological symptoms of Dementia (BPSD) are commonly observed in Alzheimer's disease (AD), and strongly contribute to increasing patients' disability. Using voxel-lesion-symptom mapping (VLSM), we investigated the impact of white matter lesions (WMLs) on the severity of BPSD in patients with amnestic mild cognitive impairment (a-MCI). Thirty-one a-MCI patients (with a conversion rate to AD of 32% at 2 year follow-up) and 26 healthy controls underwent magnetic resonance imaging (MRI) examination at 3T, including T2-weighted and fluid-attenuated-inversion-recovery images, and T1-weighted volumes. In the patient group, BPSD was assessed using the Neuropsychiatric Inventory-12. After quantitative definition of WMLs, their distribution was investigated, without an a priori anatomical hypothesis, against patients' behavioural symptoms. Unbiased regional grey matter volumetrics was also used to assess the contribution of grey matter atrophy to BPSD. Apathy, irritability, depression/dysphoria, anxiety and agitation were shown to be the most common symptoms in the patient sample. Despite a more widespread anatomical distribution, a-MCI patients did not differ from controls in WML volumes. VLSM revealed a strict association between the presence of lesions in the anterior thalamic radiations (ATRs) and the severity of apathy. Regional grey matter atrophy did not account for any BPSD. This study indicates that damage to the ATRs is strategic for the occurrence of apathy in patients with a-MCI. Disconnection between the prefrontal cortex and the mediodorsal and anterior thalamic nuclei might represent the pathophysiological substrate for apathy, which is one of the most common psychopathological symptoms observed in dementia.

  4. [The thalamic syndrome of Déjérine-Roussy. Prolegomenon].

    Science.gov (United States)

    De Smet, Y

    1986-01-01

    Predicted by Dejerine and Long in 1898 and formally described by Dejerine and Roussy in 1906, the "thalamic syndrome" corrected the wrong hypothesis of a capsular "sensory cross roads" suggested by Charcot after 1873 and supported in France during 25 years. Both established the "persistent frank organic hemianesthesia" (sensory-sensitive for Charcot, pure sensitive for Dejerine), namely that a sensory deficit, still severe after regression of the early hemiplegia, could be due to focal brain damage. At that time such a clinical concept was hardly acceptable because it opposed the classic greek philosophical idea that sensation and movement should not be separated. Moreover, intelligence was at that time looked as a four-stage process including sensation, imagination, intellect and memory. The very first step began with the "sensus communis", an anteroom-like where all the sensations simultaneously perceived were coordinated to ensure mind unity. This "sensus communis" was given many subcortical seats during the following centuries, such as the trigone (Herophilus), the ventricles (Founders of the Church, Soemmering), the pineal body (Descartes), the striate bodies (Willis) and, finally, the thalamus (Todd and Carpenter's "English theory"). The description by Meynert in 1871 of a transcapsular direct "sensory bundle" and the cases reported by Türck in 1859 of a sensory-sensitive hemianesthesia after a posterior capsular lesion (in fact, thalamo-capsulostriate) led Charcot to develop his theory after 1873. Owing to the new staining methods of Weigert and Marchi introduced around 1885, Dejerine showed in 1895 the route of the medial lemniscus and his arrival in the thalamus, which led him to postulate in 1898 a "thalamic syndrome" and later to demonstrate it.

  5. Towards a theory of cortical columns: From spiking neurons to interacting neural populations of finite size.

    Directory of Open Access Journals (Sweden)

    Tilo Schwalger

    2017-04-01

    Full Text Available Neural population equations such as neural mass or field models are widely used to study brain activity on a large scale. However, the relation of these models to the properties of single neurons is unclear. Here we derive an equation for several interacting populations at the mesoscopic scale starting from a microscopic model of randomly connected generalized integrate-and-fire neuron models. Each population consists of 50-2000 neurons of the same type but different populations account for different neuron types. The stochastic population equations that we find reveal how spike-history effects in single-neuron dynamics such as refractoriness and adaptation interact with finite-size fluctuations on the population level. Efficient integration of the stochastic mesoscopic equations reproduces the statistical behavior of the population activities obtained from microscopic simulations of a full spiking neural network model. The theory describes nonlinear emergent dynamics such as finite-size-induced stochastic transitions in multistable networks and synchronization in balanced networks of excitatory and inhibitory neurons. The mesoscopic equations are employed to rapidly integrate a model of a cortical microcircuit consisting of eight neuron types, which allows us to predict spontaneous population activities as well as evoked responses to thalamic input. Our theory establishes a general framework for modeling finite-size neural population dynamics based on single cell and synapse parameters and offers an efficient approach to analyzing cortical circuits and computations.

  6. Holmes’ Tremor with Shoulder Pain Treated by Deep Brain Stimulation of Unilateral Ventral Intermediate Thalamic Nucleus and Globus Pallidus Internus

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    Sabri Aydın

    2017-05-01

    Full Text Available A 21-year-old male was admitted with severe right arm and hand tremors after a thalamic hemorrhage caused by a traffic accident. He was also suffering from agonizing pain in his right shoulder that manifested after the tremor. Neurologic examination revealed a disabling, severe, and irregular kinetic and postural tremor in the right arm during target-directed movements. There was also an irregular ipsilateral rest tremor and dystonic movements in the distal part of the right arm. The amplitude was moderate at rest and extremely high during kinetic and intentional movements. The patient underwent left globus pallidum internus and ventral intermediate thalamic nucleus deep brain stimulation. The patient improved by more than 80% as rated by the Fahn-Tolosa-Marin Tremor Rating Scale and Visual Analog Scale six months after surgery.

  7. Long-Term Effects of Anterior Thalamic Nucleus Deep Brain Stimulation on Spatial Learning in the Pilocarpine Model of Temporal Lobe Epilepsy.

    Science.gov (United States)

    Ferreira, Elenn Soares; Vieira, Laís Gabrielle; Moraes, Daniela Macedo; Amorim, Beatriz O; Malheiros, Jackeline Moraes; Hamani, Clement; Covolan, Luciene

    2018-02-01

    Cognitive impairment is a significant comorbidity of temporal lobe epilepsy that is associated with extensive hippocampal cell loss. Deep brain stimulation (DBS) of the anterior thalamic nucleus (ANT) has been used for the treatment of refractory partial seizures. In the pilocarpine model of epilepsy, ANT DBS applied during status epilepticus (SE) reduces hippocampal inflammation and apoptosis. When given to chronic epileptic animals it reduces hippocampal excitability and seizure frequency. Here, we tested whether ANT DBS delivered during SE and the silent phase of the pilocarpine model would reduce cognitive impairment when animals became chronically epileptic. SE was induced by a systemic pilocarpine injection (320 mg/kg). Immediately after SE onset, rats were assigned to receive DBS during the first six hours of SE (n = 8; DBSa group) or during SE + the silent period (i.e., 6 h/day until the animals developed the first spontaneous recurrent seizure; n = 10; DBSs group). Four months following SE, animals underwent water maze testing and histological evaluation. Nonstimulated chronic epileptic animals (n = 13; PCTL group) and age-matched naïve rats (n = 11, CTL group) were used as controls. Results were analyzed by repeated-measures analyses of variance (RM_ANOVA) and one-way ANOVAs, followed by Newman-Keuls post hoc tests. Although all groups learned the spatial task, epileptic animals with or without DBS spent significantly less time in the platform quadrant, denoting a spatial memory deficit (p < 0.02). Despite these negative behavioral results, we found that animals given DBS had a significantly higher number of cells in the CA1 region and dentate gyrus. Mossy fiber sprouting was similar among all epileptic groups. Despite lesser hippocampal neuronal loss, ANT DBS delivered either during SE or during SE and the silent phase of the pilocarpine model did not mitigate memory deficits in chronic epileptic rats. © 2017 International

  8. Thalamic superoxide and peroxide handling capacity (SPHC): An experimental study with aluminum, ethanol and tocopherol in rats.

    Science.gov (United States)

    Nayak, Prasunpriya; Sharma, S B; Chowdary, N V S

    2015-09-01

    Superoxide and peroxide handling capacity (SPHC) is an important determinant of oxidative stress. Neurotoxic impacts of aluminum are associated with oxidant imbalance. Here, we studied the influence of aluminum on oxidative stress parameters, antioxidative enzymes and SPHC of thalamic area on pro-oxidant (ethanol) and antioxidant (α-tocopherol) exposure. Two sets of male Wistar rats were divided into 8 groups (6 each) and exposed to aluminum (10 mg/Kg body wt.), ethanol (0.6 g/Kg body wt.) and α-tocopherol (5 IU/day) for 4 wk, each having respective control group. Levels of reduced glutathione (GSH), lipid peroxidation (TBARS) along with activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) of thalamic area were estimated for each group. Glutathione-independent superoxide peroxide handling capacity (GI-SPHC) and glutathione-dependent superoxide peroxide handling capacity (GD-SPHC) were calculated from the GPx, CAT and SOD values. Concomitant exposure to aluminum and ethanol demonstrated significant increase in SOD activity and significant decrease in GPx activity compared to the control group, while lone aluminum-exposed rats showed raised GR activity, without alterations in GPx and SOD activities. However, significant reduction of both GI- and GD- SPHC were found in ethanol-exposed groups. α-Tocopherol supplementation could resist most of the alterations. In addition, current antioxidant exposure reduced the inherent GD-SPHC, and thus, made thalamic area more vulnerable to oxidant threat. The present study corroborates the thalamic susceptibility to aluminum-augmented oxidant imbalance and suggests cautious use of antioxidant supplementation against neurodegenerative disorders.

  9. High field fMRI reveals thalamocortical integration of segregated cognitive and emotional processing in mediodorsal and intralaminar thalamic nuclei

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    Coraline Danielle Metzger

    2010-11-01

    Full Text Available Thalamocortical loops, connecting functionally segregated, higher order cortical regions and basal ganglia, have been proposed not only for well described motor and sensory regions, but also for limbic and prefrontal areas relevant for affective and cognitive processes. These functions are, however, more specific to humans, rendering most invasive neuroanatomical approaches impossible and interspecies translations difficult. In contrast, non invasive imaging of functional neuroanatomy using fMRI allows for the development of elaborate task paradigms capable of testing the specific functionalities proposed for these circuits. Until recently, spatial resolution largely limited the anatomical definition of functional clusters at the level of distinct thalamic nuclei. Since their anatomical distinction seems crucial not only for the segregation of cognitive and limbic loops but also for the detection of their functional interaction during cognitive-emotional integration, we applied high resolution fMRI on 7 Tesla.Using an event related design, we could isolate thalamic effects for preceding attention as well as experience of erotic stimuli. We could demonstrate specific thalamic effects of general emotional arousal in mediodorsal nucleus and effects specific to preceding attention and expectancy in intralaminar centromedian/parafascicular complex (CM/PF. These thalamic effects were paralleled by specific coactivations in the head of caudate nucleus as well as segregated portions of rostral or caudal cingulate cortex and anterior insula supporting distinct thalamo-striato-cortical loops. In addition to predescribed effects of sexual arousal in hypothalamus and ventral striatum, high resolution fMRI could extent this network to paraventricular thalamus encompassing laterodorsal and parataenial nuclei. We could lend evidence to segregated subcortical loops which integrate cognitive and emotional aspects of basic human behaviour such as sexual

  10. Pure Hemi-Chorea Resulting from an Acute Phase of Contralateral Thalamic Lacunar Infarction: A Case Report

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    Teruyuki Takahashi

    2012-11-01

    Full Text Available Background: Thalamic lesions give rise to a variety of clinical syndromes such as pure sensory stroke, ataxic hemiparesis, and rarely involuntary movements including chorea. Generally and classically, lacunar infarction in the subthalamic nucleus has been regarded as the lesion mainly responsible for hemi-chorea and hemi-ballismus, on the basis of previous anatomical studies. Case Presentation: This report describes the case of an 81-year-old man who developed sudden-onset pure hemi-chorea in the right limbs resulting from an acute phase of left thalamic lacunar infarction detected on a diffusion-weighted image (DWI in an MRI study. The patient had no other neurological symptoms such as ataxic hemiparesis and sensory disturbance. A single-photon emission computed tomography (SPECT study using the 99mTc-ECD Patlak plot method demonstrated significant perfusional asymmetry between the right and left thalami (p = 0.0035, consistent with the left thalamic lesion on DWI. Conclusion: It is speculated that this perfusional asymmetry, in particular the hypoperfusion in the left thalamus, detected by SPECT might play the most important role in the contralateral pure hemi-chorea as a rare neurological manifestation in this case.

  11. Crying spells triggered by thumb-index rubbing after thalamic stroke: a case report.

    Science.gov (United States)

    Bassani, R; Rosazza, C; Ghirardin, L; Caldiera, V; Banco, E; Casati, C; Tesio, L

    2017-02-24

    Pathologic crying, devoid of any emotional counterpart, is known to occur as a consequence of various brain stem, cortical hemispheric and cerebellar lesions or, quite exceptionally, of "dacrystic" epilepsy. The case reported here suggests that thalamic lesions may also cause crying spells, under the special circumstances described below. After a mild left thalamic stroke a caucasian 77 years old man presented with crying spells with no emotional counterpart, triggered by thumb-index rubbing of his right hand. Only a modest sensation loss on right infra-orbital and nose-labial areas and the first three right fingers could be detected at clinical examination. The circumstances and processes leading to the crying spells were investigated, together with their neural substrate. Brain computerized tomography (CT), magnetic resonance imaging (MRI) and functional magnetic resonance imaging (fMRI) were conducted. Neurophysiologic studies included Video-Electroencephalography, Electromyography, motor and sensory Evoked potentials. Active thumb-index rubbing, passive fingertips stimulation and interaction of sensory-motor stimulation with cognitive/speech activities were tested under different paradigms. A treatment with pregabalin (75 mg twice a day) was attempted. CT and MRI showed a small ischemic infarct in the left ventral postero-lateral thalamus, while fMRI led to the expected findings, i.e. a bilateral activation of the hand motor representation during the crying-triggering right-hand finger rubbing activity. Sensory potentials evoked from stimulation of the right upper limb were the only abnormal neurophysiologic test. Crying spells could be invariably evoked by both real and imagined active finger rubbing, in either the left of right hemi-space. Rubbing by an examiner was ineffective. Immersion in water (18 °C) but not oiling of the fingertips prevented the symptom. Administration and discontinuation of pregabalin 75 mg daily could be associated with

  12. Right Forceps Minor and Anterior Thalamic Radiation Predict Executive Function Skills in Young Bilingual Adults

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    Ping C. Mamiya

    2018-02-01

    Full Text Available Executive function (EF skills enhance learning across domains, and are particularly linked to the acquisition of a second language. Previous studies have shown that bilingual individuals show enhanced EF skills in cognitive tasks where they attended a targeted dimension of a stimulus while inhibiting other competing cues. Brain imaging revealed that bilingual young adults’ performances in the Stroop color-naming task were related to the volume of anterior cingulate cortex (ACC and inferior frontal lobe. Subjects who had greater white-matter in the frontal cortex showed enhanced performances in the same task, suggesting that brain fiber pathways connecting ACC to the frontal region may be related to the Stroop color-naming task. No studies to date have examined the tissue properties of brain fiber pathways connecting these brain regions and their association with subjects’ EF performances. Importantly, there are no data establishing whether bilingual subjects exhibit different reaction times when words are presented in their first versus second language. To study these questions, we used behavioral and unbiased whole-brain analyses, recruiting 21 Chinese students. Using the Stroop color-naming task, we measured subjects’ reaction times (RTs in which color names were displayed using fonts that matched the named color (congruent task or mismatched the color (incongruent task. Students performed the task twice, first in English, the subjects’ second language, then in Chinese, the subjects’ primary language. Results from whole-brain analysis showed that students’ RTs in both the English and Chinese tasks were significantly correlated with the mode of anisotropy (MO in a brain cluster containing the forceps minor and anterior thalamic radiation in the right hemisphere. We also found that fractional anisotropy (FA significantly predicted students’ RTs, with higher FA predicting shorter RT. Taken together, our findings demonstrate that

  13. Whisking-Related Changes in Neuronal Firing and Membrane Potential Dynamics in the Somatosensory Thalamus of Awake Mice

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    Nadia Urbain

    2015-10-01

    Full Text Available The thalamus transmits sensory information to the neocortex and receives neocortical, subcortical, and neuromodulatory inputs. Despite its obvious importance, surprisingly little is known about thalamic function in awake animals. Here, using intracellular and extracellular recordings in awake head-restrained mice, we investigate membrane potential dynamics and action potential firing in the two major thalamic nuclei related to whisker sensation, the ventral posterior medial nucleus (VPM and the posterior medial group (Pom, which receive distinct inputs from brainstem and neocortex. We find heterogeneous state-dependent dynamics in both nuclei, with an overall increase in action potential firing during active states. Whisking increased putative lemniscal and corticothalamic excitatory inputs onto VPM and Pom neurons, respectively. A subpopulation of VPM cells fired spikes phase-locked to the whisking cycle during free whisking, and these cells may therefore signal whisker position. Our results suggest differential processing of whisking comparing thalamic nuclei at both sub- and supra-threshold levels.

  14. Gait balance disorder by thalamic infarction with the disorder of interstitial nucleus of cajal.

    Science.gov (United States)

    Kurosu, A; Hayashi, Y; Wada, K; Nagaoka, M

    2011-01-01

    The interstitial nucleus of Cajal (INC) is thought to play an important role in torsional/vertical eye position and head posture, and disorders of the INC induce abnormal ocular movements and head tilt. Our patients with ocular tilt reactions simultaneously also had disturbances in ambulatory balance, yet no reports address the loss of balance control induced by disorders of the INC. We examined the ambulatory disturbances induced by INC lesion. We experienced three patients with ocular movement disorders and abnormal head tilt due to thalamic infarction. We performed ophthalmic examinations on and checked the balance of them. With funduscopy, abnormal cycloduction was seen in the unaffected side and normal cycloduction was observed in the affected side. Nevertheless, Hess charts showed distortions in the visual image of both eyes. They all had disorders of balance control. We tried to treat them using the Bobath approach for improving their ambulatory balance. With subsequent improvements in balance control it was possible for them to take short walks, but it was difficult to make any improvements in their ocular movement. The INC is related to balance control of ambulation and disorders of the INC induce ambulatory disturbances. Cycloduction was only observed in the unaffected side, but Hess charts showed distortions of the visual image in both eyes. Ambulation was briefly improved, but diplopia persisted in these patients.

  15. Aphasia following left thalamic hemorrhage. A study by Western Aphasia Battery and single photon emission CT

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    Makishita, Hideo; Miyasaka, Motomaro; Tanizaki, Yoshio; Yanagisawa, Nobuo; Sugishita, Morihiro

    1984-07-01

    A report is given of 7 patients with left thalamic hemorrhage in the chronic stage (from 1.5 months to 4.5 months) in which language disorders were examined by Western Aphasia Battery (WAB) and cerebral blood flow was measured by single photon emission CT. Examination of language by WAB revealed 4 aphasics out of 7 cases, and 3 patients had no language deficit. The patient with Wernicke's aphasia showed low density area only in the left posterior thalamus in X-ray CT, and revealed severe low blood flow area extending to left temporal lobe in emission CT. In the case with transcortical sensory aphasia, although X-ray CT showed no obvious low density area, emission CT revealed moderate low flow area in the left temporooccipital region and low blood flow at the left thalamus. In one of the two patients classified as anomic aphasia, emission CT showed slight low flow area at the temporo-occipital region similar to the case with transcortical sensory aphasia. In another case with anomic aphasia there was a wide low density area all over the left thalamus and midline shift to the right in X-ray CT, and emission CT showed severe low blood flow in the same region spreading widely toward the cerebral surface. In all of the 3 patients without aphasia, emission CT showed low flow region restricted to the left thalamus.

  16. Quantitative methods for evaluating the efficacy of thalamic deep brain stimulation in patients with essential tremor.

    Science.gov (United States)

    Wastensson, Gunilla; Holmberg, Björn; Johnels, Bo; Barregard, Lars

    2013-01-01

    Deep brain stimulation (DBS) of the thalamus is a safe and efficient method for treatment of disabling tremor in patient with essential tremor (ET). However, successful tremor suppression after surgery requires careful selection of stimulus parameters. Our aim was to examine the possible use of certain quantitative methods for evaluating the efficacy of thalamic DBS in ET patients in clinical practice, and to compare these methods with traditional clinical tests. We examined 22 patients using the Essential Tremor Rating Scale (ETRS) and quantitative assessment of tremor with the stimulator both activated and deactivated. We used an accelerometer (CATSYS tremor Pen) for quantitative measurement of postural tremor, and a eurythmokinesimeter (EKM) to evaluate kinetic tremor in a rapid pointing task. The efficacy of DBS on tremor suppression was prominent irrespective of the method used. The agreement between clinical rating of postural tremor and tremor intensity as measured by the CATSYS tremor pen was relatively high (rs = 0.74). The agreement between kinetic tremor as assessed by the ETRS and the main outcome variable from the EKM test was low (rs = 0.34). The lack of agreement indicates that the EKM test is not comparable with the clinical test. Quantitative methods, such as the CATSYS tremor pen, could be a useful complement to clinical tremor assessment in evaluating the efficacy of DBS in clinical practice. Future studies should evaluate the precision of these methods and long-term impact on tremor suppression, activities of daily living (ADL) function and quality of life.

  17. Evaluation of Quantitative Measurement Techniques for Head Tremor With Thalamic Deep Brain Stimulation.

    Science.gov (United States)

    Chockalingam, Arun; Boggs, Hans; Prusik, Julia; Ramirez-Zamora, Adolfo; Feustel, Paul; Belasen, Abigail; Youn, Youngwon; Fama, Chris; Haller, Jessica; Pilitsis, Julie

    2017-07-01

    Ventralis intermedius thalamic deep brain stimulation (VIM DBS) has shown to be safe and effective for medically refractory essential tremor (ET). We evaluate the use of quantitative tremor measurement methods for head tremor in ET using a "smart" hat and a smartphone application. We enrolled 13 ET patients who previously underwent VIM DBS. Head and arm tremor was measured ON and OFF stimulation using the clinical gold standard Fahn-Tolosa-Marin Tremor Rating Scale (TRS). Results were then compared to two quantitative measurement techniques: Lift Pulse (smartphone application) and modified Nizet (adapted laser point measurement from Nizet et al.). Spearman's rank correlation was used to compare tremor severity and improvement on stimulation using TRS and quantitative methods to measure tremor. Lift Pulse tremor severity measurement significantly correlated with TRS for head (ρ = 0.53, p measurement significantly correlated with TRS for head (ρ = 0.83, p measurement significantly correlated with TRS for arm tremor (ρ = 0.56, p measurement significantly correlated with TRS for head tremor (ρ = 0.53, p measure head and arm tremor severity. We also show the utility of a "smart" hat to measure head tremor. Modified Nizet technique is more effective for measuring head tremor, while Lift Pulse is an effective measure of tremor severity, especially arm tremor improvement. © 2017 International Neuromodulation Society.

  18. Gait Balance Disorder by Thalamic Infarction with the Disorder of Interstitial Nucleus of Cajal

    Science.gov (United States)

    Kurosu, A.; Hayashi, Y.; Wada, K.; Nagaoka, M.

    2011-01-01

    The interstitial nucleus of Cajal (INC) is thought to play an important role in torsional/vertical eye position and head posture, and disorders of the INC induce abnormal ocular movements and head tilt. Our patients with ocular tilt reactions simultaneously also had disturbances in ambulatory balance, yet no reports address the loss of balance control induced by disorders of the INC. We examined the ambulatory disturbances induced by INC lesion. We experienced three patients with ocular movement disorders and abnormal head tilt due to thalamic infarction. We performed ophthalmic examinations on and checked the balance of them. With funduscopy, abnormal cycloduction was seen in the unaffected side and normal cycloduction was observed in the affected side. Nevertheless, Hess charts showed distortions in the visual image of both eyes. They all had disorders of balance control. We tried to treat them using the Bobath approach for improving their ambulatory balance. With subsequent improvements in balance control it was possible for them to take short walks, but it was difficult to make any improvements in their ocular movement. The INC is related to balance control of ambulation and disorders of the INC induce ambulatory disturbances. Cycloduction was only observed in the unaffected side, but Hess charts showed distortions of the visual image in both eyes. Ambulation was briefly improved, but diplopia persisted in these patients. PMID:21769260

  19. Bilateral thalamic infarction that is secondary thrombosis to the deep venous structures: report of two cases

    Directory of Open Access Journals (Sweden)

    Serdar Oruc

    2016-12-01

    Full Text Available Deep cerebral venous thrombosis cases are the %6 of the cerebral venous thrombosis (CVT cases. The recognition of these patients is difficult since this disease is rarely observed and its clinical presentation is nonspecific and variable. In its etiology, the most frequently observed reasons are hypercoagulopathy, oral contraceptive use, pregnancy, puerperium, dehydration, and head trauma. Less frequently observed reasons are vasculitis, inflammatory bowel disease, malignancies, anemia, and tumor invasion through venous sinuses. In this report, were presented two cases who were admitted to the hospital with headache complaint and cognitive changes.According to the advanced magnetic resonance imaging, acute infarction was detected in bilateral thalamus. We observed CVT with adversely affected deep cerebral venous system structures. CVT development was associated with the use of oral contraceptives in the first case and it was associated with anemia in the second case. Both patients were discharged from the hospital upon healing with anticoagulant therapy. In this study, it has been emphasized by representing these two patients that CVT should be thought in the etiology of bilateral thalamic ischemia. Furthermore, it is also crucial to known that these patients can be fully improved clinically and radiologically in case appropriate medical treatment is applied.

  20. Comorbid Asperger and Tourette syndromes with localized mesencephalic, infrathalamic, thalamic, and striatal damage.

    Science.gov (United States)

    Berthier, Marcelo L; Kulisevsky, Jaime; Asenjo, Beatriz; Aparicio, Jesús; Lara, Diego

    2003-03-01

    We describe the coexistence of Asperger and Tourette syndromes (AS and TS) caused by discrete hypoxic-ischaemic necrosis of the midbrain, infrathalamic and thalamic nuclei, and striatum in an adolescent male with positive family history for tics and obsessive-compulsive disorder. Behavioural ratings, cognitive tests, and volumetric measurements of the basal ganglia were performed in the patient and five other individuals with AS-TS unassociated with MRI lesions. Cognitive deficits in attentional, executive, and visual-spatial domains were found both in the patient and control AS-TS group, though deficits were more severe in the former. MRI showed reduction of the left basal ganglia volume compared with the right in the patient, whereas the control group showed reduction of right basal ganglia volume compared with the left. It is suggested that individuals with a genetic predisposition to TS may develop AS and TS after involvement of midbrain and related components of basal ganglia-thalamocortical circuits normally implicated in the integration of emotional, cognitive, and motor functions.

  1. Impaired spatial working memory after anterior thalamic lesions: recovery with cerebrolysin and enrichment.

    Science.gov (United States)

    Loukavenko, Elena A; Wolff, Mathieu; Poirier, Guillaume L; Dalrymple-Alford, John C

    2016-05-01

    Lesions to the anterior thalamic nuclei (ATN) in rats produce robust spatial memory deficits that reflect their influence as part of an extended hippocampal system. Recovery of spatial working memory after ATN lesions was examined using a 30-day administration of the neurotrophin cerebrolysin and/or an enriched housing environment. As expected, ATN lesions in standard-housed rats given saline produced severely impaired reinforced spatial alternation when compared to standard-housed rats with sham lesions. Both cerebrolysin and enrichment substantially improved this working memory deficit, including accuracy on trials that required attention to distal cues for successful performance. The combination of cerebrolysin and enrichment was more effective than either treatment alone when the delay between successive runs in a trial was increased to 40 s. Compared to the intact rats, ATN lesions in standard-housed groups produced substantial reduction in c-Fos expression in the retrosplenial cortex, which remained low after cerebrolysin and enrichment treatments. Evidence that multiple treatment strategies restore some memory functions in the current lesion model reinforces the prospect for treatments in human diencephalic amnesia.

  2. Ophthalmoplegic migraine with reversible thalamic ischemia by Tc-99m ethylcysteinate dimer brain SPECT

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    Kim, Jong Ho; Shin, Dong Jin; Kang, Sung Soo [Gachon Medical School, Gil Medical Center, Inchon (Korea, Republic of)

    1999-07-01

    Two patients presented with ophthalmoplegic migraine (OM) underwent EEG, Brain-MRI, cerebral angiography, and Tc-99m ECD SPECT during an attack. Follow-up SPECT was performed after neurologic symptoms resolved. In both cases, SPECT during an attack of ophthalmoplegia and headache demonstrated a significantly decreased regional cerebral blood flow in the thalamus to the side of ophthalmoplegia, which was normalized on the follow-up SPECT during a symptom free recovery phase (Lesion to Non-lesion thalamic ratio=1.19 to 0.96 and 1.16 to 0.98, respectively). The other roentgenographic and laboratory findings were normal. These findings are suggestive the ischemia in the perforators of PCA results in third nerve palsy because the portion of oculomotor nerve behind the cavernous sinus derives its blood supply from small perforating branches of the basilar and PCA. Matched ictal hypoperfusion of the thalamus to the site of ophthalmoplegic migraine is suggestive of the ischemic neuropathy as an etiology of OM.

  3. Distinct kinetics of inhibitory currents in thalamocortical neurons that arise from dendritic or axonal origin.

    Directory of Open Access Journals (Sweden)

    Sunggu Yang

    Full Text Available Thalamocortical neurons in the dorsal lateral geniculate nucleus (dLGN transfer visual information from retina to primary visual cortex. This information is modulated by inhibitory input arising from local interneurons and thalamic reticular nucleus (TRN neurons, leading to alterations of receptive field properties of thalamocortical neurons. Local GABAergic interneurons provide two distinct synaptic outputs: axonal (F1 terminals and dendritic (F2 terminals onto dLGN thalamocortical neurons. By contrast, TRN neurons provide only axonal output (F1 terminals onto dLGN thalamocortical neurons. It is unclear if GABAA receptor-mediated currents originating from F1 and F2 terminals have different characteristics. In the present study, we examined multiple characteristics (rise time, slope, halfwidth and decay τ of GABAA receptor-mediated miniature inhibitory postsynaptic synaptic currents (mIPSCs originating from F1 and F2 terminals. The mIPSCs arising from F2 terminals showed slower kinetics relative to those from F1 terminals. Such differential kinetics of GABAAR-mediated responses could be an important role in temporal coding of visual signals.

  4. Selective neuronal lapses precede human cognitive lapses following sleep deprivation.

    Science.gov (United States)

    Nir, Yuval; Andrillon, Thomas; Marmelshtein, Amit; Suthana, Nanthia; Cirelli, Chiara; Tononi, Giulio; Fried, Itzhak

    2017-12-01

    Sleep deprivation is a major source of morbidity with widespread health effects, including increased risk of hypertension, diabetes, obesity, heart attack, and stroke. Moreover, sleep deprivation brings about vehicle accidents and medical errors and is therefore an urgent topic of investigation. During sleep deprivation, homeostatic and circadian processes interact to build up sleep pressure, which results in slow behavioral performance (cognitive lapses) typically attributed to attentional thalamic and frontoparietal circuits, but the underlying mechanisms remain unclear. Recently, through study of electroencephalograms (EEGs) in humans and local field potentials (LFPs) in nonhuman primates and rodents it was found that, during sleep deprivation, regional 'sleep-like' slow and theta (slow/theta) waves co-occur with impaired behavioral performance during wakefulness. Here we used intracranial electrodes to record single-neuron activities and LFPs in human neurosurgical patients performing a face/nonface categorization psychomotor vigilance task (PVT) over multiple experimental sessions, including a session after full-night sleep deprivation. We find that, just before cognitive lapses, the selective spiking responses of individual neurons in the medial temporal lobe (MTL) are attenuated, delayed, and lengthened. These 'neuronal lapses' are evident on a trial-by-trial basis when comparing the slowest behavioral PVT reaction times to the fastest. Furthermore, during cognitive lapses, LFPs exhibit a relative local increase in slow/theta activity that is correlated with degraded single-neuron responses and with baseline theta activity. Our results show that cognitive lapses involve local state-dependent changes in neuronal activity already present in the MTL.

  5. Quantitative Methods for Evaluating the Efficacy of Thalamic Deep Brain Stimulation in Patients with Essential Tremor

    Science.gov (United States)

    Wastensson, Gunilla; Holmberg, Björn; Johnels, Bo; Barregard, Lars

    2013-01-01

    Background Deep brain stimulation (DBS) of the thalamus is a safe and efficient method for treatment of disabling tremor in patient with essential tremor (ET). However, successful tremor suppression after surgery requires careful selection of stimulus parameters. Our aim was to examine the possible use of certain quantitative methods for evaluating the efficacy of thalamic DBS in ET patients in clinical practice, and to compare these methods with traditional clinical tests. Methods We examined 22 patients using the Essential Tremor Rating Scale (ETRS) and quantitative assessment of tremor with the stimulator both activated and deactivated. We used an accelerometer (CATSYS tremor Pen) for quantitative measurement of postural tremor, and a eurythmokinesimeter (EKM) to evaluate kinetic tremor in a rapid pointing task. Results The efficacy of DBS on tremor suppression was prominent irrespective of the method used. The agreement between clinical rating of postural tremor and tremor intensity as measured by the CATSYS tremor pen was relatively high (rs = 0.74). The agreement between kinetic tremor as assessed by the ETRS and the main outcome variable from the EKM test was low (rs = 0.34). The lack of agreement indicates that the EKM test is not comparable with the clinical test. Discussion Quantitative methods, such as the CATSYS tremor pen, could be a useful complement to clinical tremor assessment in evaluating the efficacy of DBS in clinical practice. Future studies should evaluate the precision of these methods and long-term impact on tremor suppression, activities of daily living (ADL) function and quality of life. PMID:24255800

  6. Active action potential propagation but not initiation in thalamic interneuron dendrites

    Science.gov (United States)

    Casale, Amanda E.; McCormick, David A.

    2012-01-01

    Inhibitory interneurons of the dorsal lateral geniculate nucleus of the thalamus modulate the activity of thalamocortical cells in response to excitatory input through the release of inhibitory neurotransmitter from both axons and dendrites. The exact mechanisms by which release can occur from dendrites are, however, not well understood. Recent experiments using calcium imaging have suggested that Na/K based action potentials can evoke calcium transients in dendrites via local active conductances, making the back-propagating action potential a candidate for dendritic neurotransmitter release. In this study, we employed high temporal and spatial resolution voltage-sensitive dye imaging to assess the characteristics of dendritic voltage deflections in response to Na/K action potentials in interneurons of the mouse dorsal lateral geniculate nucleus. We found that trains or single action potentials elicited by somatic current injection or local synaptic stimulation led to action potentials that rapidly and actively back-propagated throughout the entire dendritic arbor and into the fine filiform dendritic appendages known to release GABAergic vesicles. Action potentials always appeared first in the soma or proximal dendrite in response to somatic current injection or local synaptic stimulation, and the rapid back-propagation into the dendritic arbor depended upon voltage-gated sodium and TEA-sensitive potassium channels. Our results indicate that thalamic interneuron dendrites integrate synaptic inputs that initiate action potentials, most likely in the axon initial segment, that then back-propagate with high-fidelity into the dendrites, resulting in a nearly synchronous release of GABA from both axonal and dendritic compartments. PMID:22171033

  7. Outcome based definition of the anterior thalamic deep brain stimulation target in refractory epilepsy.

    Science.gov (United States)

    Lehtimäki, K; Möttönen, T; Järventausta, K; Katisko, J; Tähtinen, T; Haapasalo, J; Niskakangas, T; Kiekara, T; Öhman, J; Peltola, J

    2016-01-01

    Deep brain stimulation of the anterior nucleus of the thalamus (ANT) is an emerging therapy for refractory focal epilepsy. However, the most optimal target for stimulation has not been unambiguously described. In the present study, we investigated the correlation between the stimulation site and outcome in order to define the optimal target for deep brain stimulation in refractory epilepsy. The locations of 62 contacts used in 30 treatment attempts in 15 prospectively followed patients during a 5 year period were assessed. Treatment attempts were classified into responding and non-responding trials using seizure reduction and side effect profile as criteria. The locations of active contacts were calculated with respect to mid-commissural point and visible borders of ANT in 3T MRI (ANT-normalized coordinate system) aiming to minimize the confounding effect of individual variation in the location and size of the ANT. Contacts in successful treatment trials were located significantly more anterior and superior both in AC-PC and ANT-normalized coordinate systems. Favourable outcome was observed at 3T MRI based location of ANT but not at location predicted by Schaltenbrandt atlas sagittal data. Contacts used in successful trials were at anterior aspect of the ANT complex evidenced by the ANT-normalized coordinate system. The anti-epileptic effect of anterior thalamic DBS may be dependent on stimulation site especially in the anterior to posterior axis. Extensive anatomical variation confounds severely the targeting of ANT. Therefore, direct visualization of the desired target for stimulation is essential for favourable outcome in refractory epilepsy. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Localization of Basal Ganglia and Thalamic Damage in Dyskinetic Cerebral Palsy.

    Science.gov (United States)

    Aravamuthan, Bhooma R; Waugh, Jeff L

    2016-01-01

    Dyskinetic cerebral palsy affects 15%-20% of patients with cerebral palsy. Basal ganglia injury is associated with dyskinetic cerebral palsy, but the patterns of injury within the basal ganglia predisposing to dyskinetic cerebral palsy are unknown, making treatment difficult. For example, deep brain stimulation of the globus pallidus interna improves dystonia in only 40% of patients with dyskinetic cerebral palsy. Basal ganglia injury heterogeneity may explain this variability. To investigate this, we conducted a qualitative systematic review of basal ganglia and thalamic damage in dyskinetic cerebral palsy. Reviews and articles primarily addressing genetic or toxic causes of cerebral palsy were excluded yielding 22 studies (304 subjects). Thirteen studies specified the involved basal ganglia nuclei (subthalamic nucleus, caudate, putamen, globus pallidus, or lentiform nuclei, comprised by the putamen and globus pallidus). Studies investigating the lentiform nuclei (without distinguishing between the putamen and globus pallidus) showed that all subjects (19 of 19) had lentiform nuclei damage. Studies simultaneously but independently investigating the putamen and globus pallidus also showed that all subjects (35 of 35) had lentiform nuclei damage (i.e., putamen or globus pallidus damage); this was followed in frequency by damage to the putamen alone (70 of 101, 69%), the subthalamic nucleus (17 of 25, 68%), the thalamus (88 of 142, 62%), the globus pallidus (7/35, 20%), and the caudate (6 of 47, 13%). Globus pallidus damage was almost always coincident with putaminal damage. Noting consistent involvement of the lentiform nuclei in dyskinetic cerebral palsy, these results could suggest two groups of patients with dyskinetic cerebral palsy: those with putamen-predominant damage and those with panlenticular damage involving both the putamen and the globus pallidus. Differentiating between these groups could help predict response to therapies such as deep brain

  9. Decreased striatal and enhanced thalamic dopaminergic responsivity in detoxified cocaine abusers

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    Volkow, N.D.; Wang, G.J.; Fowler, J.S. [Brookhaven National Lab., Stony Brook, NY (United States)] [and others

    1997-05-01

    It has been hypothesized that cocaine addiction could result from decreased brain dopamine (DA) function. However, little is known about changes in (DA) neurotransmission in human cocaine addiction. We used PET and [C-11]raclopride, a DA D2 receptor ligand sensitive to competition with endogenous DA, to measure relative changes in extracellular DA induced by methylphenidate (MP) in 20 cocaine abusers (3-6 weeks after cocaine discontinuation) and 23 controls. MP did not affect the transport of [C-11]raclopride from blood to brain (K1); however it induced a significant reduction in DA D2 receptor availability (Bmax/Kd) in striatum. The magnitude of ND-induced changes in striatal [C-11]raclopride binding were significantly larger in controls (21 + 13% change from baseline) than in cocaine abusers (9 {+-} 13 %) (ANOVA p < 0.005). In cocaine abusers, but not in controls, MP also decreased Bmax/Kd values in thalamus (29 {+-} 35 %) (ANOVA p < 0.005). There were no differences in plasma MP concentration between the groups. In striatum MP-induced changes in Bmax/Kd were significantly correlated with MP-induced changes in self reports of restlessness (r = 0.49, df 42, p < 0.002). In thalamus MP-induced changes in Bmax/Kd were significantly correlated with ND-induced changes in self reports of cocaine craving (r = 0.57, df 42, p < 0.0001). These results are compatible with a decrease in striatal DA brain function in cocaine abusers. They also suggest a participation of thalamic DA pathways in cocaine addiction.

  10. Lateral Thalamic Eminence: A Novel Origin for mGluR1/Lot Cells.

    Science.gov (United States)

    Ruiz-Reig, Nuria; Andrés, Belén; Huilgol, Dhananjay; Grove, Elizabeth A; Tissir, Fadel; Tole, Shubha; Theil, Thomas; Herrera, Eloisa; Fairén, Alfonso

    2017-05-01

    A unique population of cells, called "lot cells," circumscribes the path of the lateral olfactory tract (LOT) in the rodent brain and acts to restrict its position at the lateral margin of the telencephalon. Lot cells were believed to originate in the dorsal pallium (DP). We show that Lhx2 null mice that lack a DP show a significant increase in the number of mGluR1/lot cells in the piriform cortex, indicating a non-DP origin of these cells. Since lot cells present common developmental features with Cajal-Retzius (CR) cells, we analyzed Wnt3a- and Dbx1-reporter mouse lines and found that mGluR1/lot cells are not generated in the cortical hem, ventral pallium, or septum, the best characterized sources of CR cells. Finally, we identified a novel origin for the lot cells by combining in utero electroporation assays and histochemical characterization. We show that mGluR1/lot cells are specifically generated in the lateral thalamic eminence and that they express mitral cell markers, although a minority of them express ΔNp73 instead. We conclude that most mGluR1/lot cells are prospective mitral cells migrating to the accessory olfactory bulb (OB), whereas mGluR1+, ΔNp73+ cells are CR cells that migrate through the LOT to the piriform cortex and the OB. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. Resting state functional thalamic connectivity abnormalities in patients with post-stroke sleep apnoea: a pilot case-control study.

    Science.gov (United States)

    Sacchetti, M L; Di Mascio, M T; Tinelli, E; Mainero, C; Russo, G; Fiorelli, M; Calistri, V; de Lena, C; Minni, A; Caramia, F

    2017-06-01

    Sleep apnoea is common after stroke, and has adverse effects on the clinical outcome of affected cases. Its pathophysiological mechanisms are only partially known. Increases in brain connectivity after stroke might influence networks involved in arousal modulation and breathing control. The aim of this study was to investigate the resting state functional MRI thalamic hyper-connectivity of stroke patients affected by sleep apnoea (SA) with respect to cases not affected, and to healthy controls (HC). A series of stabilized strokes were submitted to 3T resting state functional MRI imaging and full polysomnography. The ventral-posterior-lateral thalamic nucleus was used as seed. At the between groups comparison analysis, in SA cases versus HC, the regions significantly hyper-connected with the seed were those encoding noxious threats (frontal eye field, somatosensory association, secondary visual cortices). Comparisons between SA cases versus those without SA revealed in the former group significantly increased connectivity with regions modulating the response to stimuli independently to their potentiality of threat (prefrontal, primary and somatosensory association, superolateral and medial-inferior temporal, associative and secondary occipital ones). Further significantly functionally hyper-connections were documented with regions involved also in the modulation of breathing during sleep (pons, midbrain, cerebellum, posterior cingulate cortices), and in the modulation of breathing response to chemical variations (anterior, posterior and para-hippocampal cingulate cortices). Our preliminary data support the presence of functional hyper connectivity in thalamic circuits modulating sensorial stimuli, in patients with post-stroke sleep apnoea, possibly influencing both their arousal ability and breathing modulation during sleep.

  12. Connectivity-based parcellation of the thalamus explains specific cognitive and behavioural symptoms in patients with bilateral thalamic infarct.

    Directory of Open Access Journals (Sweden)

    Laura Serra

    Full Text Available A novel approach based on diffusion tractography was used here to characterise the cortico-thalamic connectivity in two patients, both presenting with an isolated bilateral infarct in the thalamus, but exhibiting partially different cognitive and behavioural profiles. Both patients (G.P. and R.F. had a pervasive deficit in episodic memory, but only one of them (R.F. suffered also from a dysexecutive syndrome. Both patients had an MRI scan at 3T, including a T1-weighted volume. Their lesions were manually segmented. T1-volumes were normalised to standard space, and the same transformations were applied to the lesion masks. Nineteen healthy controls underwent a diffusion-tensor imaging (DTI scan. Their DTI data were normalised to standard space and averaged. An atlas of Brodmann areas was used to parcellate the prefrontal cortex. Probabilistic tractography was used to assess the probability of connection between each voxel of the thalamus and a set of prefrontal areas. The resulting map of corticothalamic connections was superimposed onto the patients' lesion masks, to assess whether the location of the thalamic lesions in R.F. (but not in G. P. implied connections with prefrontal areas involved in dysexecutive syndromes. In G.P., the lesion fell within areas of the thalamus poorly connected with prefrontal areas, showing only a modest probability of connection with the anterior cingulate cortex (ACC. Conversely, R.F.'s lesion fell within thalamic areas extensively connected with the ACC bilaterally, with the right dorsolateral prefrontal cortex, and with the left supplementary motor area. Despite a similar, bilateral involvement of the thalamus, the use of connectivity-based segmentation clarified that R.F.'s lesions only were located within nuclei highly connected with the prefrontal cortical areas, thus explaining the patient's frontal syndrome. This study confirms that DTI tractography is a useful tool to examine in vivo the effect of focal

  13. Connectivity-based parcellation of the thalamus explains specific cognitive and behavioural symptoms in patients with bilateral thalamic infarct.

    Science.gov (United States)

    Serra, Laura; Cercignani, Mara; Carlesimo, Giovanni A; Fadda, Lucia; Tini, Nadia; Giulietti, Giovanni; Caltagirone, Carlo; Bozzali, Marco

    2014-01-01

    A novel approach based on diffusion tractography was used here to characterise the cortico-thalamic connectivity in two patients, both presenting with an isolated bilateral infarct in the thalamus, but exhibiting partially different cognitive and behavioural profiles. Both patients (G.P. and R.F.) had a pervasive deficit in episodic memory, but only one of them (R.F.) suffered also from a dysexecutive syndrome. Both patients had an MRI scan at 3T, including a T1-weighted volume. Their lesions were manually segmented. T1-volumes were normalised to standard space, and the same transformations were applied to the lesion masks. Nineteen healthy controls underwent a diffusion-tensor imaging (DTI) scan. Their DTI data were normalised to standard space and averaged. An atlas of Brodmann areas was used to parcellate the prefrontal cortex. Probabilistic tractography was used to assess the probability of connection between each voxel of the thalamus and a set of prefrontal areas. The resulting map of corticothalamic connections was superimposed onto the patients' lesion masks, to assess whether the location of the thalamic lesions in R.F. (but not in G. P.) implied connections with prefrontal areas involved in dysexecutive syndromes. In G.P., the lesion fell within areas of the thalamus poorly connected with prefrontal areas, showing only a modest probability of connection with the anterior cingulate cortex (ACC). Conversely, R.F.'s lesion fell within thalamic areas extensively connected with the ACC bilaterally, with the right dorsolateral prefrontal cortex, and with the left supplementary motor area. Despite a similar, bilateral involvement of the thalamus, the use of connectivity-based segmentation clarified that R.F.'s lesions only were located within nuclei highly connected with the prefrontal cortical areas, thus explaining the patient's frontal syndrome. This study confirms that DTI tractography is a useful tool to examine in vivo the effect of focal lesions on

  14. Unilateral asterixis, thalamic astasia and vertical one and half syndrome in a unilateral posterior thalamo-subthalamic paramedian infarct: An interesting case report

    Directory of Open Access Journals (Sweden)

    Subasree Ramakrishnan

    2013-01-01

    Full Text Available A 42-year-old young lady presented with acute onset of dizziness, drooping of left eye with binocular diplopia and inability to walk unassisted. She had past history of uncontrolled diabetes mellitus and hypertension. On examination, she had left fascicular type of third nerve palsy, vertical one and half syndrome (VOHS, left internuclear ophthalmoplegia and skew deviation with ipsilesional hypertropia. She also had thalamic astasia and right unilateral asterixis. Her MRI revealed T2 and Flair hyper intense signal changes with restricted diffusion in the left thalamus, subthalamus and left midbrain. MR Angiography was normal. Thalamic-subthalamic paramedian territory infarct is relatively uncommon. It can present with oculomotor abnormalities including vertical one and half syndrome, skew deviation, thalamic astasia and asterixis. This case is reported for the rarity of the presenting clinical findings in unilateral thalamo-mesencephalic infarcts.

  15. Juvenil neuronal ceroid lipofuscinosis

    DEFF Research Database (Denmark)

    Ostergaard, J R; Hertz, Jens Michael

    1998-01-01

    Neuronal ceroid-lipofuscinosis is a group of neurodegenerative diseases which are characterized by an abnormal accumulation of lipopigment in neuronal and extraneuronal cells. The diseases can be differentiated into several subgroups according to age of onset, the clinical picture...

  16. Detection of secondary thalamic degeneration after cortical infarction using cis-4-18F-fluoro-D-proline.

    Science.gov (United States)

    Langen, Karl-Josef; Salber, Dagmar; Hamacher, Kurt; Stoffels, Gabriele; Reifenberger, Guido; Pauleit, Dirk; Coenen, Heinz H; Zilles, Karl

    2007-09-01

    The amino acid cis-4-(18)F-fluoro-D-proline (D-cis-(18)F-FPro) exhibits preferential uptake in the brain compared with its L-isomer, but the clinical potential of the tracer is as yet unknown. In this study we explored the cerebral uptake of D-cis-(18)F-FPro in rats with focal cortical infarctions. Focal cortical infarctions were induced in different areas of the cortex of 20 Fisher CDF rats by photothrombosis (PT). At variable time points after PT (1 d to 4 wk), the rats were injected intravenously with D-cis-(18)F-FPro. For comparison, 12 rats were injected simultaneously with (3)H-deoxyglucose ((3)H-DG), 3 rats were injected with (3)H-methyl-L-methionine ((3)H-MET), and 2 rats were injected with (3)H-PK11195. Within 2 h after injection of the tracers, coronal cryosections of the brains were produced and evaluated by dual-tracer autoradiography. Lesion-to-brain ratios (L/B ratios) were calculated by dividing the maximal uptake in areas with increased tracer uptake by the mean uptake in normal brain tissue. Histologic slices were stained by toluidine blue and by immunostainings for glial fibrillary acidic protein (GFAP), CD68 for macrophages, and CD11b for microglia. Prominent uptake of D-cis-(18)F-FPro was found in ipsilateral thalamic nuclei (TN) and partially in the corpus striatum starting at 3 d after infarction with increasing L/B ratios up to 4 wk (mean L/B ratio +/- SD, 6.7 +/- 3.5). The involved TN varied with the site of the cortical lesion corresponding to their thalamocortical projections connecting them with their specific target region in the cerebral cortex. The TN were positive for CD11b and GFAP from day 7 onward, whereas uptake of (3)H-DG, (3)H-MET, and (3)H-PK11195 and immunostaining for CD68 were similar to that of normal brain. Furthermore, increased uptake of D-cis-(18)F-FPro was found in the area of the cortical infarctions (mean L/B ratio +/- SD, 12.1 +/- 8.1). From day 5 onward, the pattern of uptake was congruent with that of

  17. A vital role of tubulin-tyrosine-ligase for neuronal organization

    Science.gov (United States)

    Erck, Christian; Peris, Leticia; Andrieux, Annie; Meissirel, Claire; Gruber, Achim D.; Vernet, Muriel; Schweitzer, Annie; Saoudi, Yasmina; Pointu, Hervé; Bosc, Christophe; Salin, Paul A.; Job, Didier; Wehland, Juergen

    2005-01-01

    Tubulin is subject to a special cycle of detyrosination/tyrosination in which the C-terminal tyrosine of α-tubulin is cyclically removed by a carboxypeptidase and readded by a tubulin-tyrosine-ligase (TTL). This tyrosination cycle is conserved in evolution, yet its physiological importance is unknown. Here, we find that TTL suppression in mice causes perinatal death. A minor pool of tyrosinated (Tyr-)tubulin persists in TTL null tissues, being present mainly in dividing TTL null cells where it originates from tubulin synthesis, but it is lacking in postmitotic TTL null cells such as neurons, which is apparently deleterious because early death in TTL null mice is, at least in part, accounted for by a disorganization of neuronal networks, including a disruption of the cortico-thalamic loop. Correlatively, cultured TTL null neurons display morphogenetic anomalies including an accelerated and erratic time course of neurite outgrowth and a premature axonal differentiation. These anomalies may involve a mislocalization of CLIP170, which we find lacking in neurite extensions and growth cones of TTL null neurons. Our results demonstrate a vital role of TTL for neuronal organization and suggest a requirement of Tyr-tubulin for proper control of neurite extensions. PMID:15899979

  18. Selective pharmacological manipulation of cortical-thalamic co-cultures in a dual-compartment device

    NARCIS (Netherlands)

    Kanagasabapathi, T.T.; Franco, M.; Barone, R.A.; Martinoia, S.; Wadman, W.J.; Decré, M.M.J.

    2013-01-01

    In this study, we demonstrate capabilities to selectively manipulate dissociated co-cultures of neurons plated in dual-compartment devices. Synaptic receptor antagonists and tetrodotoxin solutions were used to selectively control and study the network-wide burst propagation and cell firing in

  19. State transitions between wake and sleep, and within the ultradian cycle, with focus on the link to neuronal activity.

    Science.gov (United States)

    Merica, Helli; Fortune, Ronald D

    2004-12-01

    The structure of sleep across the night as expressed by the hypnogram, is characterised by repeated transitions between the different states of vigilance: wake, light and deep non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep. This review is concerned with current knowledge on these state transitions, focusing primarily on those findings that allow the integration of data at cellular level with spectral time-course data at the encephalographic (EEG) level. At the cellular level it has been proposed that, under the influence of circadian and homeostatic factors, transitions between wake and sleep may be determined by mutually inhibitory interaction between sleep-active neurons in the hypothalamic preoptic area and wake-active neurons in multiple arousal centres. These two fundamentally different behavioural states are separated by the sleep onset and the sleep inertia periods each characterised by gradual changes in which neither true wake nor true sleep patterns are present. The results of sequential spectral analysis of EEG data on moves towards and away from deep sleep are related to findings at the cellular level on the generating mechanisms giving rise to the various NREM oscillatory modes under the neuromodulatory control of brainstem-thalamic activating systems. And there is substantial evidence at cellular level that transition to and from REM sleep is governed by the reciprocal interaction between cholinergic REM-on neurons and aminergic REM-off neurons located in the brainstem. Similarity between the time-course of the REM-on neuronal activity and that of EEG power in the high beta range (approximately 18-30 Hz) allows a tentative parallelism to be drawn between the two. This review emphasises the importance of the thalamically projecting brainstem activating systems in the orchestration of the transitions that give rise to state progression across the sleep-wake cycle.

  20. Altered functional network architecture in orbitofronto-striato-thalamic circuit of unmedicated patients with obsessive-compulsive disorder.

    Science.gov (United States)

    Jung, Wi Hoon; Yücel, Murat; Yun, Je-Yeon; Yoon, Youngwoo B; Cho, Kang Ik K; Parkes, Linden; Kim, Sung Nyun; Kwon, Jun Soo

    2017-01-01

    Dysfunction of corticostriatal loops has been proposed to underlie certain cognitive and behavioral problems associated with various neuropsychiatric disorders, such as obsessive-compulsive disorder (OCD) characterized by repetitive, unwanted thoughts, and behaviors. Although functional abnormalities in the loops involving the orbitofronto-striato-thalamic (OFST) circuitry in patients with OCD have been reported, our understanding of a link between disruptions in the architecture of the intrinsic functional network of the OFST circuit and their symptoms remain incomplete. Using resting-state functional MRI in conjunction with unsupervised clustering and multilevel functional connectivity (FC) techniques, FC of the OFST network and its topological organization in 61 OCD patients versus 61 matched controls were characterized. Patients exhibited disruptions in small-world properties of the OFST circuit, which indicates an imbalance between functional integration and segregation. Patients also showed decreased FC between the central orbitofrontal cortex and dorsomedial striatum but increased FC between the medial thalamus and striatal areas. Using one of the largest samples of unmedicated OCD patients to date, our findings provide evidence supporting the OFST dysconnection hypothesis in OCD as a basic pathophysiological mechanism underlying the disorder, showing the disruption of FC between specific cortical, striatal, and thalamic clusters and aberrant topological patterns of the OFST circuit. Hum Brain Mapp 38:109-119, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  1. The pacemaker role of thalamic reticular nucleus in controlling spike-wave discharges and spindles

    Science.gov (United States)

    Fan, Denggui; Liao, Fucheng; Wang, Qingyun

    2017-07-01

    Absence epilepsy, characterized by 2-4 Hz spike-wave discharges (SWDs), can be caused by pathological interactions within the thalamocortical system. Cortical spindling oscillations are also demonstrated to involve the oscillatory thalamocortical rhythms generated by the synaptic circuitry of the thalamus and cortex. This implies that SWDs and spindling oscillations can share the common thalamocortical mechanism. Additionally, the thalamic reticular nucleus (RE) is hypothesized to regulate the onsets and propagations of both the epileptic SWDs and sleep spindles. Based on the proposed single-compartment thalamocortical neural field model, we firstly investigate the stimulation effect of RE on the initiations, terminations, and transitions of SWDs. It is shown that the activations and deactivations of RE triggered by single-pulse stimuli can drive the cortical subsystem to behave as the experimentally observed onsets and self-abatements of SWDs, as well as the transitions from 2-spike and wave discharges (2-SWDs) to SWDs. In particular, with increasing inhibition from RE to the specific relay nucleus (TC), rich transition behaviors in cortex can be obtained through the upstream projection path, RE → TC → Cortex . Although some of the complex dynamical patterns can be expected from the earlier single compartment thalamocortical model, the effect of brain network topology on the emergence of SWDs and spindles, as well as the transitions between them, has not been fully investigated. We thereby develop a spatially extended 3-compartment coupled network model with open-/closed-end connective configurations, to investigate the spatiotemporal effect of RE on the SWDs and spindles. Results show that the degrees of activations of RE 1 can induce the rich spatiotemporal evolution properties including the propagations from SWDs to spindles within different compartments and the transitions between them, through the RE 1 → TC 1 → Cortex 1 and Cortex 1 → Cortex 2

  2. Social cognitive and neurocognitive deficits in inpatients with unilateral thalamic lesions — pilot study

    Directory of Open Access Journals (Sweden)

    Wilkos E

    2015-04-01

    Full Text Available Ewelina Wilkos,2 Timothy JB Brown,3 Ksenia Slawinska,1 Katarzyna A Kucharska2,3 1Department of Neurology, 2Department of Neuroses, Personality and Eating Disorders Institute of Psychiatry and Neurology, Warsaw, Poland; 3Department of Medical Education, Hull York Medical School, Hull, UK Background: The essential role of the thalamus in neurocognitive processes has been well documented. In contrast, relatively little is known about its involvement in social cognitive processes such as recognition of emotion, mentalizing, or empathy. The aim of the study: This study was designed to compare the performance of eight patients (five males, three females, mean age ± SD: 63.7±7.9 years at early stage of unilateral thalamic lesions and eleven healthy controls (six males, five females, 49.6±12.2 years in neurocognitive tests (CogState Battery: Groton Maze Learning Test, GML; Groton Maze Learning Test-Delayed Recall, GML-DR; Detection Task, DT; Identification Task, IT; One Card Learning Task, OCLT; One Back Task, OBT; Two Back Task, TBT; Set-Shifting Task, S-ST and other well-known tests (Benton Visual Retention Test, BVRT; California Verbal Learning Test, CVLT; The Rey-Osterrieth Complex Figure Test, ROCF; Trail Making Test, TMT part A and B; Color – Word Stroop Task, CWST; Verbal Fluency Test, VFT, and social cognitive tasks (The Penn Emotion Recognition Test, ER40; Penn Emotion Discrimination Task, EmoDiff40; The Penn Emotional Acuity Test, PEAT40; Reading the Mind in the Eyes Test, revised version II; Toronto Alexithymia Scale, TAS-20. Methods: Thalamic-damaged subjects were included if they experienced a single-episode ischemic stroke localized in right or left thalamus. The patients were examined at 3 weeks after the stroke onset. All were right handed. In addition, the following clinical scales were used: the Mini-Mental State Examination (MMSE, Spielberger State-Trait Anxiety Inventory (STAI, Beck Depression Inventory (BDI II. An inclusion

  3. Responses of MST neurons to plaid stimuli.

    Science.gov (United States)

    Khawaja, Farhan A; Liu, Liu D; Pack, Christopher C

    2013-07-01

    The estimation of motion information from retinal input is a fundamental function of the primate dorsal visual pathway. Previous work has shown that this function involves multiple cortical areas, with each area integrating information from its predecessors. Compared with neurons in the primary visual cortex (V1), neurons in the middle temporal (MT) area more faithfully represent the velocity of plaid stimuli, and the observation of this pattern selectivity has led to two-stage models in which MT neurons integrate the outputs of component-selective V1 neurons. Motion integration in these models is generally complemented by motion opponency, which refines velocity selectivity. Area MT projects to a third stage of motion processing, the medial superior temporal (MST) area, but surprisingly little is known about MST responses to plaid stimuli. Here we show that increased pattern selectivity in MST is associated with greater prevalence of the mechanisms implemented by two-stage MT models: Compared with MT neurons, MST neurons integrate motion components to a greater degree and exhibit evidence of stronger motion opponency. Moreover, when tested with more challenging unikinetic plaid stimuli, an appreciable percentage of MST neurons are pattern selective, while such selectivity is rare in MT. Surprisingly, increased motion integration is found in MST even for transparent plaid stimuli, which are not typically integrated perceptually. Thus the relationship between MST and MT is qualitatively similar to that between MT and V1, as repeated application of basic motion mechanisms leads to novel selectivities at each stage along the pathway.

  4. Measurement of frontal lobe volume and thalamic volume in fetuses with congenital heart disease at different gestational weeks using three dimensional ultra sonography and its clinical value.

    Science.gov (United States)

    Li-Fei, Zhu; Hong-Xiong, Liu; Ying, H E

    2016-11-01

    Our study aimed to investigate the measurement of frontal lobe volume and thalamic volume in fetuses with congenital heart disease (CHD) at different gestational weeks using three dimensional (3-D) ultrasonography and its clinical value. Then, 238 pregnant women who received obstetric ultrasonography in ultrasound department of Internal Medicine of our hospital were enrolled between March 2013 to April 2014. In this study, 85 fetuses were diagnosed to develop CHD by prenatal fetal echocardiography, and the other 153 fetuses were normal. Frontal lobe volume, thalamic volume and cerebral blood flow was determined by color Doppler ultrasonic diagnostic apparatus (type: GE Voluson E8). The level of MCA-PI and CPR in CHD fetus group performed significantly lower than that in normal fetus group (Pfrontal lobe volume between the two groups (Pfrontal lobe volume than that in normal fetus group (Pfrontal lobe volume and thalamic volume; if gestational age frontal lobe volume and thalamic volume in fetuses with CHD performed significantly lower than that in normal fetuses.

  5. The Medial Dorsal Thalamic Nucleus and the Medial Prefrontal Cortex of the Rat Function Together to Support Associative Recognition and Recency but Not Item Recognition

    Science.gov (United States)

    Cross, Laura; Brown, Malcolm W.; Aggleton, John P.; Warburton, E. Clea

    2013-01-01

    In humans recognition memory deficits, a typical feature of diencephalic amnesia, have been tentatively linked to mediodorsal thalamic nucleus (MD) damage. Animal studies have occasionally investigated the role of the MD in single-item recognition, but have not systematically analyzed its involvement in other recognition memory processes. In…

  6. Intraganglionic interactions between satellite cells and adult sensory neurons.

    Science.gov (United States)

    Christie, Kimberly; Koshy, Dilip; Cheng, Chu; Guo, GuiFang; Martinez, Jose A; Duraikannu, Arul; Zochodne, Douglas W

    2015-07-01

    Perineuronal satellite cells have an intimate anatomical relationship with sensory neurons that suggests close functional collaboration and mutual support. We examined several facets of this relationship in adult sensory dorsal root ganglia (DRG). Collaboration included the support of process outgrowth by clustering of satellite cells, induction of distal branching behavior by soma signaling, the capacity of satellite cells to respond to distal axon injury of its neighboring neurons, and evidence of direct neuron-satellite cell exchange. In vitro, closely adherent coharvested satellite cells routinely clustered around new outgrowing processes and groups of satellite cells attracted neurite processes. Similar clustering was encountered in the pseudounipolar processes of intact sensory neurons within intact DRG in vivo. While short term exposure of distal growth cones of unselected adult sensory neurons to transient gradients of a PTEN inhibitor had negligible impacts on their behavior, exposure of the soma induced early and substantial growth of their distant neurites and branches, an example of local soma signaling. In turn, satellite cells sensed when distal neuronal axons were injured by enlarging and proliferating. We also observed that satellite cells were capable of internalizing and expressing a neuron fluorochrome label, diamidino yellow, applied remotely to distal injured axons of the neuron and retrogradely transported to dorsal root ganglia sensory neurons. The findings illustrate a robust interaction between intranganglionic neurons and glial cells that involve two way signals, features that may be critical for both regenerative responses and ongoing maintenance. Copyright © 2015. Published by Elsevier Inc.

  7. Diverse coupling of neurons to populations in sensory cortex.

    Science.gov (United States)

    Okun, Michael; Steinmetz, Nicholas; Cossell, Lee; Iacaruso, M Florencia; Ko, Ho; Barthó, Péter; Moore, Tirin; Hofer, Sonja B; Mrsic-Flogel, Thomas D; Carandini, Matteo; Harris, Kenneth D

    2015-05-28

    A large population of neurons can, in principle, produce an astronomical number of distinct firing patterns. In cortex, however, these patterns lie in a space of lower dimension, as if individual neurons were "obedient members of a huge orchestra". Here we use recordings from the visual cortex of mouse (Mus musculus) and monkey (Macaca mulatta) to investigate the relationship between individual neurons and the population, and to establish the underlying circuit mechanisms. We show that neighbouring neurons can differ in their coupling to the overall firing of the population, ranging from strongly coupled 'choristers' to weakly coupled 'soloists'. Population coupling is largely independent of sensory preferences, and it is a fixed cellular attribute, invariant to stimulus conditions. Neurons with high population coupling are more strongly affected by non-sensory behavioural variables such as motor intention. Population coupling reflects a causal relationship, predicting the response of a neuron to optogenetically driven increases in local activity. Moreover, population coupling indicates synaptic connectivity; the population coupling of a neuron, measured in vivo, predicted subsequent in vitro estimates of the number of synapses received from its neighbours. Finally, population coupling provides a compact summary of population activity; knowledge of the population couplings of n neurons predicts a substantial portion of their n(2) pairwise correlations. Population coupling therefore represents a novel, simple measure that characterizes the relationship of each neuron to a larger population, explaining seemingly complex network firing patterns in terms of basic circuit variables.

  8. Complementary processing of haptic information by slowly and rapidly adapting neurons in the trigeminothalamic pathway. Electrophysiology, mathematical modeling and simulations of vibrissae-related neurons.

    Directory of Open Access Journals (Sweden)

    Abel eSanchez-Jimenez

    2013-06-01

    Full Text Available Tonic (slowly adapting and phasic (rapidly adapting primary afferents convey complementary aspects of haptic information to the central nervous system: object location and texture the former, shape the latter. Tonic and phasic neural responses are also recorded in all relay stations of the somatosensory pathway, yet it is unknown their role in both, information processing and information transmission to the cortex: we don’t know if tonic and phasic neurons process complementary aspects of haptic information and/or if these two types constitute two separate channels that convey complementary aspects of tactile information to the cortex. Here we propose to elucidate these two questions in the fast trigeminal pathway of the rat (PrV-VPM: principal trigeminal nucleus-ventroposteromedial thalamic nucleus. We analyze early and global behavior, latencies and stability of the responses of individual cells in PrV and medial lemniscus under 1-40 Hz stimulation of the whiskers in control and decorticated animals and we use stochastic spiking models and extensive simulations. Our results strongly suggest that in the first relay station of the somatosensory system (PrV: 1 tonic and phasic neurons process complementary aspects of whisker-related tactile information 2 tonic and phasic responses are not originated from two different types of neurons 3 the two responses are generated by the differential action of the somatosensory cortex on a unique type of PrV cell 4 tonic and phasic neurons do not belong to two different channels for the transmission of tactile information to the thalamus 5 trigeminothalamic transmission is exclusively performed by tonically firing neurons and 6 all aspects of haptic information are coded into low-pass, band-pass and high-pass filtering profiles of tonically firing neurons. Our results are important for both, basic research on neural circuits and information processing, and development of sensory neuroprostheses.

  9. Maternal endotoxin exposure results in abnormal neuronal architecture in the newborn rabbit.

    Science.gov (United States)

    Balakrishnan, Bindu; Dai, Hui; Janisse, James; Romero, Roberto; Kannan, Sujatha

    2013-01-01

    Maternal intrauterine inflammation/infection is a potential risk factor for the development of neurologic disorders such as cerebral palsy (CP) in preterm and term infants. CP is associated with white matter and grey matter injury. In the current study, we used a rabbit model of CP in which pregnant rabbits are administered intrauterine injections of the endotoxin lipopolysaccharide. We then investigated the extent of neuronal damage in the newborn kit brain. We observed an overall decrease in the number of MAP2-stained neurons and an increase in Fluoro-Jade C-stained cells in the anterior thalamus of 1-day-old rabbit brain. We also observed an overall decrease in the number of branching points and spine density in the retrosplenial cortex, a major output region of the anterior thalamus that is involved in cognition and memory. The loss of spines and dendritic atrophy in the retrosplenial cortex may be caused by loss of presynaptic input from the thalamus. Our study indicates that the cognitive impairments seen in patients with CP may be related to the degeneration of neurons and abnormal arborization of the thalamic and cortical neurons.

  10. Barreloid Borders and Neuronal Activity Shape Panglial Gap Junction-Coupled Networks in the Mouse Thalamus.

    Science.gov (United States)

    Claus, Lena; Philippot, Camille; Griemsmann, Stephanie; Timmermann, Aline; Jabs, Ronald; Henneberger, Christian; Kettenmann, Helmut; Steinhäuser, Christian

    2018-01-01

    The ventral posterior nucleus of the thalamus plays an important role in somatosensory information processing. It contains elongated cellular domains called barreloids, which are the structural basis for the somatotopic organization of vibrissae representation. So far, the organization of glial networks in these barreloid structures and its modulation by neuronal activity has not been studied. We have developed a method to visualize thalamic barreloid fields in acute slices. Combining electrophysiology, immunohistochemistry, and electroporation in transgenic mice with cell type-specific fluorescence labeling, we provide the first structure-function analyses of barreloidal glial gap junction networks. We observed coupled networks, which comprised both astrocytes and oligodendrocytes. The spread of tracers or a fluorescent glucose derivative through these networks was dependent on neuronal activity and limited by the barreloid borders, which were formed by uncoupled or weakly coupled oligodendrocytes. Neuronal somata were distributed homogeneously across barreloid fields with their processes running in parallel to the barreloid borders. Many astrocytes and oligodendrocytes were not part of the panglial networks. Thus, oligodendrocytes are the cellular elements limiting the communicating panglial network to a single barreloid, which might be important to ensure proper metabolic support to active neurons located within a particular vibrissae signaling pathway. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. [Nerve growth factor and the physiology of pain: the relationships among interoception, sympathetic neurons and the emotional response indicated by the molecular pathophysiology of congenital insensitivity to pain with anhidrosis].

    Science.gov (United States)

    Indo, Yasuhiro

    2015-05-01

    Nerve growth factor (NGF) is a neurotrophic factor essential for the survival and maintenance of neurons. Congenital insensitivity to pain with anhidrosis (CIPA) is caused by loss-of-function mutations in NTRK1, which encodes a receptor tyrosine kinase, TrkA, for NGF. Mutations in NTRK1 cause the selective loss of NGF-dependent neurons, including both NGF-dependent primary afferents and sympathetic postganglionic neurons, in otherwise intact systems. The NGF-dependent primary afferents are thinly myelinated AΔ or unmyelinated C-fibers that are dependent on the NGF-TrkA system during development. NGF-dependent primary afferents are not only nociceptive neurons that transmit pain and temperature sensation, but also are polymodal receptors that play essential roles for interoception by monitoring various changes in the physiological status of all tissues in the body. In addition, they contribute to various inflammatory processes in acute, chronic and allergic inflammation. Together with sympathetic postganglionic neurons, they maintain the homeostasis of the body and emotional responses via interactions with the brain, immune and endocrine systems. Pain is closely related to emotions that accompany physical responses induced by systemic activation of the sympathetic nervous system. In contrast to a negative image of emotions in daily life, Antonio Damasio proposed the 'Somatic Marker Hypothesis', wherein emotions play critical roles in the decision-making and reasoning processes. According to this hypothesis, reciprocal communication between the brain and the body-proper are essential for emotional responses. Using the pathophysiology of CIPA as a foundation, this article suggests that NGF-dependent neurons constitute a part of the neuronal network required for homeostasis and emotional responses, and indicates that this network plays important roles in mediating the reciprocal communication between the brain and the body-proper.

  12. On the genesis of spike-wave oscillations in a mean-field model of human thalamic and corticothalamic dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues, Serafim [Department of Mathematical Sciences, Loughborough University, Leicestershire, LE11 3TU (United Kingdom); Terry, John R. [Department of Mathematical Sciences, Loughborough University, Leicestershire, LE11 3TU (United Kingdom)]. E-mail: j.r.terry@lboro.ac.uk; Breakspear, Michael [Black Dog Institute, Randwick, NSW 2031 (Australia); School of Psychiatry, UNSW, NSW 2030 (Australia)

    2006-07-10

    In this Letter, the genesis of spike-wave activity-a hallmark of many generalized epileptic seizures-is investigated in a reduced mean-field model of human neural activity. Drawing upon brain modelling and dynamical systems theory, we demonstrate that the thalamic circuitry of the system is crucial for the generation of these abnormal rhythms, observing that the combination of inhibition from reticular nuclei and excitation from the cortical signal, interplay to generate the spike-wave oscillation. The mechanism revealed provides an explanation of why approaches based on linear stability and Heaviside approximations to the activation function have failed to explain the phenomena of spike-wave behaviour in mean-field models. A mathematical understanding of this transition is a crucial step towards relating spiking network models and mean-field approaches to human brain modelling.

  13. Abnormal Ocular Movement With Executive Dysfunction and Personality Change in Subject With Thalamic Infarction: A Case Report.

    Science.gov (United States)

    Kim, Ee Jin; Kim, Myeong Ok; Kim, Chang Hwan; Joa, Kyung Lim; Jung, Han Young

    2015-12-01

    The thalamus, located between the cerebrum and midbrain, is a nuclear complex connected to the cerebral cortex that influences motor skills, cognition, and mood. The thalamus is composed of 50-60 nuclei and can be divided into four areas according to vascular supply. In addition, it can be divided into five areas according to function. Many studies have reported on a thalamic infarction causing motor or sensory changes, but few have reported on behavioral and executive aspects of the ophthalmoplegia of the thalamus. This study reports a rare case of a paramedian thalamus infarction affecting the dorsomedial area of the thalamus, manifesting as oculomotor nerve palsy, an abnormal behavioral change, and executive dysfunction. This special case is presented with a review of the anatomical basis and function of the thalamus.

  14. Impaired macromolecular protein pools in fronto-striato-thalamic circuits in type 2 diabetes revealed by magnetization transfer imaging.

    Science.gov (United States)

    Yang, Shaolin; Ajilore, Olusola; Wu, Minjie; Lamar, Melissa; Kumar, Anand

    2015-01-01

    Previous research has shown that type 2 diabetes mellitus (T2DM) is associated with white matter microstructural changes, cognitive impairment, and decreased resting-state functional connectivity and spontaneous brain activity. This study used magnetization transfer imaging to examine, for the first time, the integrity of macromolecular protein pools in fronto-striato-thalamic circuits and its clinical and cognitive correlates in patients with T2DM. T2DM patients without mood disorders (n = 20, aged 65.05 ± 11.95 years) and healthy control subjects (HCs; n = 26, aged 62.92 ± 12.71 years) were recruited. Nodes of fronto-striato-thalamic circuits-head of the caudate nucleus (hCaud), putamen, globus pallidus, thalamus-and four cortical regions-rostral and dorsal anterior cingulate cortex, dorsolateral prefrontal cortex, and lateral orbitofrontal cortex-were examined. Compared with HCs, patients with T2DM had significantly lower magnetization transfer ratio (MTR) in bilateral anterior cingulate and hCaud. Reduced MTRs in the above regions showed correlations with T2DM-related clinical measures, including hemoglobin A1c level and vascular risk factors, and neuropsychological task performance in the domains of learning and memory, executive function, and attention and information processing. The impaired biophysical integrity of brain macromolecular protein pools and their local microenvironments in T2DM patients may provide insights into the neurological pathophysiology underlying diabetes-associated clinical and cognitive deficits. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  15. Electrical stimulation of the inferior thalamic peduncle in the treatment of major depression and obsessive compulsive disorders.

    Science.gov (United States)

    Jiménez, Fiacro; Nicolini, Humberto; Lozano, Andres M; Piedimonte, Fabián; Salín, Rafael; Velasco, Francisco

    2013-01-01

    Stimulation of the inferior thalamic peduncle (ITP) is emerging as a promising new therapeutic target in certain psychiatric disorders. The circuitry that includes the nonspecific thalamic system (NSTS), which projects via the ITP to the orbitofrontal cortex (OFC), is involved in the physiopathology of major depression disorder (MDD) and obsessive compulsive disorder (OCD). The safety and efficacy of chronic ITP stimulation in cases of MDD and OCD refractory to medical treatment is presented. Six patients with OCD and one with MDD were implanted with tetrapolar deep brain stimulation electrodes in the ITP (x = 3.5 mm lateral to the ventricular wall, y = 5 mm behind the anterior commissure, and z = at the intercommissural plane, i.e., anterior commissure-posterior commissure [AC-PC] level). The effect of chronic stimulation at 130 Hz, 450 μs, and 5.0 V on OCD was evaluated before and 3, 6, and 12 months after initiation of electrical stimulation through the Yale-Brown Obsessive Compulsive Scale, Hamilton Depression Rating Scale, and Global Assessment of Function scale. Chronic ITP electrical stimulation in OCD patients decreased the mean Yale-Brown Obsessive Compulsive Scale score to around 51% for the group at the 12-month follow-up, and increased the mean Global Assessment of Function scale score to 68% for a significant improvement (P = 0.026). Three of 6 patients returned to work. The Hamilton Depression Rating Scale score of the only patient with MDD treated to date went from 42 to 6. This condition of the patient, who had been incapacitated for 5 years prior to surgery, has not relapsed for 9 years. Three OCD patients with drug addiction continued to consume drugs in spite of their improvement in OCD. Deep brain stimulation in the ITP is safe and may be effective in the treatment of OCD. A multicenter evaluation of the safety and efficacy of ITP in OCD is currently in process. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Neuronal mechanisms and circuits underlying repetitive behaviors in mouse models of autism spectrum disorder.

    Science.gov (United States)

    Kim, Hyopil; Lim, Chae-Seok; Kaang, Bong-Kiun

    2016-01-20

    Autism spectrum disorder (ASD) refers to a broad spectrum of neurodevelopmental disorders characterized by three central behavioral symptoms: impaired social interaction, impaired social communication, and restricted and repetitive behaviors. However, the symptoms are heterogeneous among patients and a number of ASD mouse models have been generated containing mutations that mimic the mutations found in human patients with ASD. Each mouse model was found to display a unique set of repetitive behaviors. In this review, we summarize the repetitive behaviors of the ASD mouse models and variations found in their neural mechanisms including molecular and electrophysiological features. We also propose potential neuronal mechanisms underlying these repetitive behaviors, focusing on the role of the cortico-basal ganglia-thalamic circuits and brain regions associated with both social and repetitive behaviors. Further understanding of molecular and circuitry mechanisms of the repetitive behaviors associated with ASD is necessary to aid the development of effective treatments for these disorders.

  17. NEURON and Python.

    Science.gov (United States)

    Hines, Michael L; Davison, Andrew P; Muller, Eilif

    2009-01-01

    The NEURON simulation program now allows Python to be used, alone or in combination with NEURON's traditional Hoc interpreter. Adding Python to NEURON has the immediate benefit of making available a very extensive suite of analysis tools written for engineering and science. It also catalyzes NEURON software development by offering users a modern programming tool that is recognized for its flexibility and power to create and maintain complex programs. At the same time, nothing is lost because all existing models written in Hoc, including graphical user interface tools, continue to work without change and are also available within the Python context. An example of the benefits of Python availability is the use of the xml module in implementing NEURON's Import3D and CellBuild tools to read MorphML and NeuroML model specifications.

  18. Progranulin regulates neuronal outgrowth independent of Sortilin

    Directory of Open Access Journals (Sweden)

    Gass Jennifer

    2012-07-01

    Full Text Available Abstract Background Progranulin (PGRN, a widely secreted growth factor, is involved in multiple biological functions, and mutations located within the PGRN gene (GRN are a major cause of frontotemporal lobar degeneration with TDP-43-positive inclusions (FLTD-TDP. In light of recent reports suggesting PGRN functions as a protective neurotrophic factor and that sortilin (SORT1 is a neuronal receptor for PGRN, we used a Sort1-deficient (Sort1−/− murine primary hippocampal neuron model to investigate whether PGRN’s neurotrophic effects are dependent on SORT1. We sought to elucidate this relationship to determine what role SORT1, as a regulator of PGRN levels, plays in modulating PGRN’s neurotrophic effects. Results As the first group to evaluate the effect of PGRN loss in Grn knockout primary neuronal cultures, we show neurite outgrowth and branching are significantly decreased in Grn−/− neurons compared to wild-type (WT neurons. More importantly, we also demonstrate that PGRN overexpression can rescue this phenotype. However, the recovery in outgrowth is not observed following treatment with recombinant PGRN harboring missense mutations p.C139R, p.P248L or p.R432C, indicating that these mutations adversely affect the neurotrophic properties of PGRN. In addition, we also present evidence that cleavage of full-length PGRN into granulin peptides is required for increased neuronal outgrowth, suggesting that the neurotrophic functions of PGRN are contained within certain granulins. To further characterize the mechanism by which PGRN impacts neuronal morphology, we assessed the involvement of SORT1. We demonstrate that PGRN induced-outgrowth occurs in the absence of SORT1 in Sort1−/− cultures. Conclusion We demonstrate that loss of PGRN impairs proper neurite outgrowth and branching, and that exogenous PGRN alleviates this impairment. Furthermore, we determined that exogenous PGRN induces outgrowth independent of SORT1, suggesting another

  19. Functional diversity of layer IV spiny neurons in rat somatosensory cortex: quantitative morphology of electrophysiologically characterized and biocytin labeled cells.

    Science.gov (United States)

    Staiger, Jochen F; Flagmeyer, Iris; Schubert, Dirk; Zilles, Karl; Kötter, Rolf; Luhmann, Heiko J

    2004-06-01

    Previous analyses of the spiny layer IV neurons have almost exclusively focused on spiny stellate cells. Here we provide detailed morphological data characterizing three subpopulations of spiny neurons in slices of adolescent rats: (i) spiny stellate cells (58%), (ii) star pyramidal cells (25%) and (iii) pyramidal cells (17%), which can be distinguished objectively by the preferential orientation of their dendritic stems. Spiny stellate cells lacked an apical dendrite and frequently confined their dendritic and axonal arbors to the respective column. Star pyramidal and pyramidal cells possessed an apical dendrite, which reached the supragranular layers. Their axonal arbors were similar, showing both a columnar component and transcolumnar branches with direct transbarrel projections. However, a small fraction of star pyramidal cells possessed few or even no transcolumnar branches. Electrophysiologically, all three types of neurons were either regular-spiking or intrinsically burst-spiking without a significant relation to the morphological subtypes. The basic synaptic properties of thalamic inputs were also independent of the type of target layer IV spiny neuron. All remained subthreshold and showed paired-pulse depression. In conclusion, the columnar axonal arborization of spiny stellate cells is supplemented by a significant oblique to horizontal projection pattern in pyramidal-like neurons. This offers a structural basis for either segregation or early context-dependent integration of tactile information, in a cell-type specific manner.

  20. Bursting activity of substantia nigra pars reticulata neurons in mouse parkinsonism in awake and anesthetized states.

    Science.gov (United States)

    Lobb, C J; Jaeger, D

    2015-03-01

    Electrophysiological changes in basal ganglia neurons are hypothesized to underlie motor dysfunction in Parkinson's disease (PD). Previous results in head-restrained MPTP-treated non-human primates have suggested that increased bursting within the basal ganglia and related thalamic and cortical areas may be a hallmark of pathophysiological activity. In this study, we investigated whether there is increased bursting in substantia nigra pars reticulata (SNpr) output neurons in anesthetized and awake, head-restrained unilaterally lesioned 6-OHDA mice when compared to control mice. Confirming previous studies, we show that there are significant changes in the firing rate and pattern in SNpr neuron activity under urethane anesthesia. The regular firing pattern of control urethane-anesthetized SNpr neurons was not present in the 6-OHDA-lesioned group, as the latter neurons instead became phase locked with cortical slow wave activity (SWA). Next, we examined whether such robust electrophysiological changes between groups carried over to the awake state. SNpr neurons from both groups fired at much higher frequencies in the awake state than in the anesthetized state and surprisingly showed only modest changes between awake control and 6-OHDA groups. While there were no differences in firing rate between groups in the awake state, an increase in the coefficient of variation (CV) was observed in the 6-OHDA group. Contrary to the bursting hypothesis, this increased CV was not due to changes in bursting but was instead due to a mild increase in pausing. Together, these results suggest that differences in SNpr activity between control and 6-OHDA lesioned mice may be strongly influenced by changes in network activity during different arousal and behavioral states. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Single neuron computation

    CERN Document Server

    McKenna, Thomas M; Zornetzer, Steven F

    1992-01-01

    This book contains twenty-two original contributions that provide a comprehensive overview of computational approaches to understanding a single neuron structure. The focus on cellular-level processes is twofold. From a computational neuroscience perspective, a thorough understanding of the information processing performed by single neurons leads to an understanding of circuit- and systems-level activity. From the standpoint of artificial neural networks (ANNs), a single real neuron is as complex an operational unit as an entire ANN, and formalizing the complex computations performed by real n

  2. CACNA1H missense mutations associated with amyotrophic lateral sclerosis alter Ca(v)3.2 T-type calcium channel activity and reticular thalamic neuron firing

    Czech Academy of Sciences Publication Activity Database

    Rzhepetskyy, Yuriy; Lazniewska, Joanna; Blesneac, I.; Pamphlett, R.; Weiss, Norbert

    2016-01-01

    Roč. 10, č. 6 (2016), s. 466-477 ISSN 1933-6950 R&D Projects: GA ČR GA15-13556S; GA MŠk 7AMB15FR015 Institutional support: RVO:61388963 Keywords : ALS * amyotrophic lateral sclerosis * biophysics * CACNA1H * Ca(v)3 * 2 channel Subject RIV: CE - Biochemistry Impact factor: 2.042, year: 2016

  3. Neuromorphic Silicon Neuron Circuits

    Science.gov (United States)

    Indiveri, Giacomo; Linares-Barranco, Bernabé; Hamilton, Tara Julia; van Schaik, André; Etienne-Cummings, Ralph; Delbruck, Tobi; Liu, Shih-Chii; Dudek, Piotr; Häfliger, Philipp; Renaud, Sylvie; Schemmel, Johannes; Cauwenberghs, Gert; Arthur, John; Hynna, Kai; Folowosele, Fopefolu; Saighi, Sylvain; Serrano-Gotarredona, Teresa; Wijekoon, Jayawan; Wang, Yingxue; Boahen, Kwabena

    2011-01-01

    Hardware implementations of spiking neurons can be extremely useful for a large variety of applications, ranging from high-speed modeling of large-scale neural systems to real-time behaving systems, to bidirectional brain–machine interfaces. The specific circuit solutions used to implement silicon neurons depend on the application requirements. In this paper we describe the most common building blocks and techniques used to implement these circuits, and present an overview of a wide range of neuromorphic silicon neurons, which implement different computational models, ranging from biophysically realistic and conductance-based Hodgkin–Huxley models to bi-dimensional generalized adaptive integrate and fire models. We compare the different design methodologies used for each silicon neuron design described, and demonstrate their features with experimental results, measured from a wide range of fabricated VLSI chips. PMID:21747754

  4. Neuromorphic Silicon Neuron Circuits

    National Research Council Canada - National Science Library

    Indiveri, Giacomo; Linares-Barranco, Bernabé; Hamilton, Tara Julia; Schaik, André van; Etienne-Cummings, Ralph; Delbruck, Tobi; Liu, Shih-Chii; Dudek, Piotr; Häfliger, Philipp; Renaud, Sylvie; Schemmel, Johannes; Cauwenberghs, Gert; Arthur, John; Hynna, Kai; Folowosele, Fopefolu; Saighi, Sylvain; Serrano-Gotarredona, Teresa; Wijekoon, Jayawan; Wang, Yingxue; Boahen, Kwabena

    2011-01-01

    Hardware implementations of spiking neurons can be extremely useful for a large variety of applications, ranging from high-speed modeling of large-scale neural systems to real-time behaving systems...

  5. Neuromorphic silicon neuron circuits

    Directory of Open Access Journals (Sweden)

    Giacomo eIndiveri

    2011-05-01

    Full Text Available Hardware implementations of spiking neurons can be extremely useful for a large variety of applications, ranging from high-speed modeling of large-scale neural systems to real-time behaving systems, to bidirectional brain-machine interfaces. The specific circuit solutions used to implement silicon neurons depend on the application requirements. In this paper we describe the most common building blocks and techniques used to implement these circuits, and present an overview of a wide range of neuromorphic silicon neurons, which implement different computational models, ranging from biophysically realistic and conductance based Hodgkin-Huxley models to bi-dimensional generalized adaptive Integrate and Fire models. We compare the different design methodologies used for each silicon neuron design described, and demonstrate their features with experimental results, measured from a wide range of fabricated VLSI chips.

  6. Neuronal functional connection graphs among multiple areas of the rat somatosensory system during spontaneous and evoked activities.

    Directory of Open Access Journals (Sweden)

    Antonio G Zippo

    Full Text Available Small-World Networks (SWNs represent a fundamental model for the comprehension of many complex man-made and biological networks. In the central nervous system, SWN models have been shown to fit well both anatomical and functional maps at the macroscopic level. However, the functional microscopic level, where the nodes of a network are represented by single neurons, is still poorly understood. At this level, although recent evidences suggest that functional connection graphs exhibit small-world organization, it is not known whether and how these maps, potentially distributed in multiple brain regions, change across different conditions, such as spontaneous and stimulus-evoked activities. We addressed these questions by analyzing the data from simultaneous multi-array extracellular recordings in three brain regions of rats, diversely involved in somatosensory information processing: the ventropostero-lateral thalamic nuclei, the primary somatosensory cortex and the centro-median thalamic nuclei. From both spike and Local Field Potential (LFP recordings, we estimated the functional connection graphs by using the Normalized Compression Similarity for spikes and the Phase Synchrony for LFPs. Then, by using graph-theoretical statistics, we characterized the functional topology both during spontaneous activity and sensory stimulation. Our main results show that: (i spikes and LFPs show SWN organization during spontaneous activity; (ii after stimulation onset, while substantial functional graph reconfigurations occur both in spike and LFPs, small-worldness is nonetheless preserved; (iii the stimulus triggers a significant increase of inter-area LFP connections without modifying the topology of intra-area functional connections. Finally, investigating computationally the functional substrate that supports the observed phenomena, we found that (iv the fundamental concept of cell assemblies, transient groups of activating neurons, can be described by small

  7. Impaired prefronto-thalamic functional connectivity as a key feature of treatment-resistant depression: a combined MEG, PET and rTMS study.

    Directory of Open Access Journals (Sweden)

    Cheng-Ta Li

    Full Text Available Prefrontal left-right functional imbalance and disrupted prefronto-thalamic circuitry are plausible mechanisms for treatment-resistant depression (TRD. Add-on repetitive transcranial magnetic stimulation (rTMS, effective in treating antidepressant-refractory TRD, was administered to verify the core mechanisms underlying the refractoriness to antidepressants. Thirty TRD patients received a 2-week course of 10-Hz rTMS to the left dorsolateral prefrontal cortex (DLPFC. Depression scores were evaluated at baseline (W0, and the ends of weeks 1, 2, and 14 (W14. Responders were defined as those who showed an objective improvement in depression scores ≥50% after rTMS. Left-right frontal alpha asymmetry (FAA was measured by magnetoencephalography at each time point as a proxy for left-right functional imbalance. Prefronto-thalamic connections at W0 and W14 were assessed by studying couplings between prefrontal alpha waves and thalamic glucose metabolism (PWTMC, reflecting intact thalamo-prefrontal connectivity. A group of healthy control subjects received magnetoencephalography at W0 (N = 50 to study whether FAA could have a diagnostic value for TRD, or received both magnetoencephalography and positron-emission-tomography at W0 (N = 10 to confirm the existence of PWTMC in the depression-free state. We found that FAA changes cannot differentiate between TRD and healthy subjects or between responders and non-responders. No PWTMC were found in the TRD group at W0, whereas restitution of the PWTMC was demonstrated only in the sustained responders at W14 and euthymic healthy controls. In conclusion, we affirmed impaired prefronto-thalamic functional connections, but not frontal functional imbalance, as a core deficit in TRD.

  8. Lumping Izhikevich neurons

    OpenAIRE

    Visser Sid; van Gils Stephan A

    2014-01-01

    We present the construction of a planar vector field that yields the firing rate of a bursting Izhikevich neuron can be read out, while leaving the sub-threshold behaviour intact. This planar vector field is used to derive lumped formulations of two complex heterogeneous networks of bursting Izhikevich neurons. In both cases, the lumped model is compared with the spiking network. There is excellent agreement in terms of duration and number of action potentials within the bursts, but there is ...

  9. Abnormal neuronal activity in Tourette syndrome and its modulation using deep brain stimulation

    Science.gov (United States)

    Israelashvili, Michal; Loewenstern, Yocheved

    2015-01-01

    Tourette syndrome (TS) is a common childhood-onset disorder characterized by motor and vocal tics that are typically accompanied by a multitude of comorbid symptoms. Pharmacological treatment options are limited, which has led to the exploration of deep brain stimulation (DBS) as a possible treatment for severe cases. Multiple lines of evidence have linked TS with abnormalities in the motor and limbic cortico-basal ganglia (CBG) pathways. Neurophysiological data have only recently started to slowly accumulate from multiple sources: noninvasive imaging and electrophysiological techniques, invasive electrophysiological recordings in TS patients undergoing DBS implantation surgery, and animal models of the disorder. These converging sources point to system-level physiological changes throughout the CBG pathway, including both general altered baseline neuronal activity patterns and specific tic-related activity. DBS has been applied to different regions along the motor and limbic pathways, primarily to the globus pallidus internus, thalamic nuclei, and nucleus accumbens. In line with the findings that also draw on the more abundant application of DBS to Parkinson's disease, this stimulation is assumed to result in changes in the neuronal firing patterns and the passage of information through the stimulated nuclei. We present an overview of recent experimental findings on abnormal neuronal activity associated with TS and the changes in this activity following DBS. These findings are then discussed in the context of current models of CBG function in the normal state, during TS, and finally in the wider context of DBS in CBG-related disorders. PMID:25925326

  10. NeuronBank: A Tool for Cataloging Neuronal Circuitry

    Science.gov (United States)

    Katz, Paul S.; Calin-Jageman, Robert; Dhawan, Akshaye; Frederick, Chad; Guo, Shuman; Dissanayaka, Rasanjalee; Hiremath, Naveen; Ma, Wenjun; Shen, Xiuyn; Wang, Hsui C.; Yang, Hong; Prasad, Sushil; Sunderraman, Rajshekhar; Zhu, Ying

    2010-01-01

    The basic unit of any nervous system is the neuron. Therefore, understanding the operation of nervous systems ultimately requires an inventory of their constituent neurons and synaptic connectivity, which form neural circuits. The presence of uniquely identifiable neurons or classes of neurons in many invertebrates has facilitated the construction of cellular-level connectivity diagrams that can be generalized across individuals within a species. Homologous neurons can also be recognized across species. Here we describe NeuronBank.org, a web-based tool that we are developing for cataloging, searching, and analyzing neuronal circuitry within and across species. Information from a single species is represented in an individual branch of NeuronBank. Users can search within a branch or perform queries across branches to look for similarities in neuronal circuits across species. The branches allow for an extensible ontology so that additional characteristics can be added as knowledge grows. Each entry in NeuronBank generates a unique accession ID, allowing it to be easily cited. There is also an automatic link to a Wiki page allowing an encyclopedic explanation of the entry. All of the 44 previously published neurons plus one previously unpublished neuron from the mollusc, Tritonia diomedea, have been entered into a branch of NeuronBank as have 4 previously published neurons from the mollusc, Melibe leonina. The ability to organize information about neuronal circuits will make this information more accessible, ultimately aiding research on these important models. PMID:20428500

  11. Bursting thalamic responses in awake monkey contribute to visual detection and are modulated by corticofugal feedback

    Directory of Open Access Journals (Sweden)

    Tania eOrtuno

    2014-05-01

    Full Text Available The lateral geniculate nucleus is the gateway for visual information en route to the visual cortex. Neural activity is characterized by the existence of 2 firing modes: burst and tonic. Originally associated with sleep, bursts have now been postulated to be a part of the normal visual response, structured to increase the probability of cortical activation, able to act as a wake-up call to the cortex. We investigated a potential role for burst in the detection of novel stimuli by recording neuronal activity in the LGN of behaving monkeys during a visual detection task. Our results show that bursts are often the neuron’s first response, and are more numerous in the response to attended target stimuli than to unattended distractor stimuli. Bursts are indicators of the task novelty, as repetition decreased bursting. Because the primary visual cortex is the major modulatory input to the LGN, we compared the results obtained in control conditions with those observed when cortical activity was reduced by TMS. This cortical deactivation reduced visual response related bursting by 90%. These results highlight a novel role for the thalamus, able to code higher order image attributes as important as novelty early in the thalamo-cortical conversation.

  12. Neuronal avalanches and learning

    Energy Technology Data Exchange (ETDEWEB)

    Arcangelis, Lucilla de, E-mail: dearcangelis@na.infn.it [Department of Information Engineering and CNISM, Second University of Naples, 81031 Aversa (Italy)

    2011-05-01

    Networks of living neurons represent one of the most fascinating systems of biology. If the physical and chemical mechanisms at the basis of the functioning of a single neuron are quite well understood, the collective behaviour of a system of many neurons is an extremely intriguing subject. Crucial ingredient of this complex behaviour is the plasticity property of the network, namely the capacity to adapt and evolve depending on the level of activity. This plastic ability is believed, nowadays, to be at the basis of learning and memory in real brains. Spontaneous neuronal activity has recently shown features in common to other complex systems. Experimental data have, in fact, shown that electrical information propagates in a cortex slice via an avalanche mode. These avalanches are characterized by a power law distribution for the size and duration, features found in other problems in the context of the physics of complex systems and successful models have been developed to describe their behaviour. In this contribution we discuss a statistical mechanical model for the complex activity in a neuronal network. The model implements the main physiological properties of living neurons and is able to reproduce recent experimental results. Then, we discuss the learning abilities of this neuronal network. Learning occurs via plastic adaptation of synaptic strengths by a non-uniform negative feedback mechanism. The system is able to learn all the tested rules, in particular the exclusive OR (XOR) and a random rule with three inputs. The learning dynamics exhibits universal features as function of the strength of plastic adaptation. Any rule could be learned provided that the plastic adaptation is sufficiently slow.

  13. IDENTIFICATION OF VESTIBULOOCULAR PROJECTION NEURONS IN THE DEVELOPING CHICKEN MEDIAL VESTIBULAR NUCLEUS

    Science.gov (United States)

    Gottesman-Davis, Adria; Peusner, Kenna D.

    2010-01-01

    Biocytin was injected into the oculomotor, trochlear, or abducens nucleus on one side using isolated chicken brainstem preparations or brain slices to identify the medial vestibular nucleus (MVN) neurons projecting to these targets. Oculomotor nucleus injections produced retrogradely labeled neurons in the contralateral ventrolateral MVN (MVNVL), with few labeled neurons in the ipsilateral MVNVL, and rarely in the dorsomedial MVN on either side. Labeled MVNVL neurons were identified as stellate (95%) and elongate cells (5%). Trochlear nucleus injections produced a similar pattern of MVN neuron labeling. Abducens nucleus injections resulted in retrogradely labeled stellate (87%) and elongate (13%) neurons in the MVNVL which had smaller cell bodies than those projecting to the oculomotor nucleus. Anteroposteriorly, labeled MVNVL neurons were coextensive with the tangential nucleus, with neurons projecting to the oculomotor nucleus distributed lateral to and intermixed with the more medially situated neurons projecting to the abducens nucleus. The fundamental pattern of vestibuloocular projecting neurons was similar at both embryonic ages studied, E16 and E13. In contrast to mammals, where most vestibuloocular projection neurons reside within the MVN, the majority of retrogradely labeled neurons in these chicken preparations were found within the ventrolateral vestibular, descending vestibular, and tangential nuclei. The morphological identification and mapping of vestibuloocular projection neurons in the chicken MVN described here represents the first step in a systematic evaluation of the relationship between avian vestibuloocular neuron structure and function. PMID:19705454

  14. Efficacy of T2*-Weighted Gradient-Echo MRI in Early Diagnosis of Cerebral Venous Thrombosis with Unilateral Thalamic Lesion

    Directory of Open Access Journals (Sweden)

    Shingo Mitaki

    2013-01-01

    Full Text Available Cerebral venous thrombosis (CVT is an uncommon cause of stroke with diverse etiologies and varied clinical presentations. Because of variability in clinical presentation and neuroimaging, CVT remains a diagnostic challenge. Recently, some studies have highlighted the value of T2*-weighted gradient-echo MRI (T2*WI in the diagnosis of CVT. We report the case of a 79-year-old woman with CVT due to a hypercoagulable state associated with cancer. On the initial T2-weighted image (T2WI, there was a diffuse high-intensity lesion in the right thalamus, extending into the posterior limb of the internal capsule and midbrain. T2*WI showed diminished signal and enlargement of the right basilar vein and the vein of Galen. Even though there is a wide range of differential diagnoses in unilateral thalamic lesions, and a single thalamus lesion is a rare entity of CVT, based on T2*WI findings we could make an early diagnosis and perform treatment. Our case report suggests that T2*WI could detect thrombosed veins and be a useful method of early diagnosis in CVT.

  15. Altered local cerebral glucose utilization induced by electrical stimulations of the thalamic sensory and parafascicular nuclei in rats.

    Science.gov (United States)

    Aiko, Y; Shima, F; Hosokawa, S; Kato, M; Kitamura, K

    1987-04-07

    Alterations in local cerebral glucose utilization (LCGU) induced by electrical stimulation of the sensory relay nucleus (VPL) or parafascicular nucleus (Pf) of the thalamus in conscious rats were measured by the [14C]2-deoxyglucose method, the objective being to assess the mechanism of analgesia induced by electrical stimulations of these structures. Stimulation of the VPL induced an ipsilateral increase in LCGU in the sensory thalamic nucleus itself, the sensory cortex and substantia nigra. Stimulation of the Pf induced bilateral increases in LCGU in the Pf and central medial nucleus of the thalamus, sensory cortex, ventral areas of the striatum and substantia nigra, and ipsilateral increase in LCGU in the periaqueductal gray, parabrachial pontine nucleus and deep layers of the superior colliculus. No significant change in LCGU was detected in the raphe dorsalis, raphe magnus and spinal dorsal horn, in both groups. Our observations coincide with clinical findings that unilateral electrical stimulation of the Pf leads to amelioration of intractable pain bilaterally, while that of the VPL induces an analgesia restricted to the contralateral side.

  16. Crossed Aphasia and Visuo-Spatial Neglect Following a Right Thalamic Stroke: A Case Study and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Lieve De Witte

    2008-01-01

    Full Text Available Crossed aphasia in dextrals (CAD following pure subcortical lesions is rare. This study describes a right-handed patient with an ischemic lesion in the right thalamus. In the post-acute phase of the stroke, a unique combination of ‘crossed thalamic aphasia’ was found with left visuo-spatial neglect and constructional apraxia. On the basis of the criteria used in Mariën et al. [67], this case-report is the first reliable representative of vascular CAD following an isolated lesion in the right thalamus. Furthermore, this paper presents a detailed analysis of linguistic and cognitive impairments of ‘possible’ and 'reliable' subcortical CAD-cases published since 1975. Out of 25 patients with a pure subcortical lesion, nine cases were considered as ‘possibly reliable or reliable’. A review of these cases reveals that: (1 demographic data are consistent with the general findings for the entire group of vascular CAD, (2 the neurolinguistic findings do not support the data in the general CAD-population with regard to (a the high prevalence of transcortical aphasia and (b the tendency towards a copresence of an oral versus written language dissociation and a ‘mirror-image’ lesion-aphasia profile, (3 subcortical CAD is not a transient phenomenon, (4 the lesion-aphasia correlations are not congruent with the high incidence of anomalous cases in the general CAD-population, (5 neuropsychological impairments may accompany subcortical CAD.

  17. The correlation of the thalamic lesions on MRI with cerebral cortical blood flow in patients with lacunar infarction

    Energy Technology Data Exchange (ETDEWEB)

    Nabatame, Hidehiko; Nakamura, Kazuo; Matsuda, Minoru; Fujimoto, Naoki [Shiga Medical Center, Moriyama (Japan); Fukuyama, Hidenao

    1995-07-01

    We performed MRI and measured cerebral blood flow (CBF) using {sup 123}I-IMP SPECT microsphere model in twenty three right-handed patients with lacunar infarction. Twelve of 23 patients showed chronic deterioration of dysarthria and gait disturbance. The mental function of the patients was evaluated by the Mini-Mental State (MMS) examination. The area of high intensity on T2-weighted images was quantitatively analyzed in the cerebral white matter (WM), lenticular nucleus (LN) and thalamus (THA). The score of MMS was positively correlated with the local CBF in the bilateral frontal, parietal, temporal and occipital cortices (p<0.05). Also, the area of high intensity in the left THA showed a significant negative correlation with local CBF of the bilateral frontal, parietal, temporal and occipital cortices (p<0.001). The high intensity areas of the bilateral LN, right WM and right THA had a significant but weaker negative correlation with local CBF of some cortices. These findings suggest that thalamic lesions on the dominant side play an important role in the reduction of cortical blood flow and the deterioration of mental functions in patients with lacunar infarction. (author).

  18. Sound-by-sound thalamic stimulation modulates midbrain auditory excitability and relative binaural sensitivity in frogs

    Directory of Open Access Journals (Sweden)

    Abhilash ePonnath

    2014-07-01

    Full Text Available Descending circuitry can modulate auditory processing, biasing sensitivity to particular stimulus parameters and locations. Using awake in vivo single unit recordings, this study tested whether electrical stimulation of the thalamus modulates auditory excitability and relative binaural sensitivity in neurons of the amphibian midbrain. In addition, by using electrical stimuli that were either longer than the acoustic stimuli (i.e., seconds or presented on a sound-by-sound basis (ms, experiments addressed whether the form of modulation depended on the temporal structure of the electrical stimulus. Following long duration electrical stimulation (3-10 s of 20 Hz square pulses, excitability (spikes / acoustic stimulus to free-field noise stimuli decreased by 32%, but returned over 600 s. In contrast, sound-by-sound electrical stimulation using a single 2 ms duration electrical pulse 25 ms before each noise stimulus caused faster and varied forms of modulation: modulation lasted < 2 s and, in different cells, excitability either decreased, increased or shifted in latency. Within cells, the modulatory effect of sound-by-sound electrical stimulation varied between different acoustic stimuli, including for different male calls, suggesting modulation is specific to certain stimulus attributes. For binaural units, modulation depended on the ear of input, as sound-by-sound electrical stimulation preceding dichotic acoustic stimulation caused asymmetric modulatory effects: sensitivity shifted for sounds at only one ear, or by different relative amounts for both ears. This caused a change in the relative difference in binaural sensitivity. Thus, sound-by-sound electrical stimulation revealed fast and ear-specific (i.e., lateralized auditory modulation that is potentially suited to shifts in auditory attention during sound segregation in the auditory scene.

  19. Sound-by-sound thalamic stimulation modulates midbrain auditory excitability and relative binaural sensitivity in frogs.

    Science.gov (United States)

    Ponnath, Abhilash; Farris, Hamilton E

    2014-01-01

    Descending circuitry can modulate auditory processing, biasing sensitivity to particular stimulus parameters and locations. Using awake in vivo single unit recordings, this study tested whether electrical stimulation of the thalamus modulates auditory excitability and relative binaural sensitivity in neurons of the amphibian midbrain. In addition, by using electrical stimuli that were either longer than the acoustic stimuli (i.e., seconds) or presented on a sound-by-sound basis (ms), experiments addressed whether the form of modulation depended on the temporal structure of the electrical stimulus. Following long duration electrical stimulation (3-10 s of 20 Hz square pulses), excitability (spikes/acoustic stimulus) to free-field noise stimuli decreased by 32%, but returned over 600 s. In contrast, sound-by-sound electrical stimulation using a single 2 ms duration electrical pulse 25 ms before each noise stimulus caused faster and varied forms of modulation: modulation lasted sound-by-sound electrical stimulation varied between different acoustic stimuli, including for different male calls, suggesting modulation is specific to certain stimulus attributes. For binaural units, modulation depended on the ear of input, as sound-by-sound electrical stimulation preceding dichotic acoustic stimulation caused asymmetric modulatory effects: sensitivity shifted for sounds at only one ear, or by different relative amounts for both ears. This caused a change in the relative difference in binaural sensitivity. Thus, sound-by-sound electrical stimulation revealed fast and ear-specific (i.e., lateralized) auditory modulation that is potentially suited to shifts in auditory attention during sound segregation in the auditory scene.

  20. Linear and non-linear fluorescence imaging of neuronal activity

    Science.gov (United States)

    Fisher, Jonathan A. N.

    Optical imaging of neuronal activity offers new possibilities for understanding brain physiology. The predominant methods in neuroscience for measuring electrical activity require electrodes inserted into the tissue. Such methods, however, provide limited spatial information and are invasive. Optical methods are less physically invasive and offer the possibility for simultaneously imaging the activity of many neurons. In this thesis one- and two-photon fluorescence microscopy techniques were applied to several in vivo and in vitro mammalian preparations. Using one-photon absorption fluorescence microscopy and gradient index (GRIN) lens optics, cortical electrical activity in response to electric stimulation was resolved in three-dimensions at high-speed in the primary somatosensory cortex of the mouse in vivo using voltage-sensitive dyes. Imaging at depths up to 150 mum below the cortex surface, it was possible to resolve depth-dependent patterns of neuronal activity in response to cortical and thalamic electric stimulation. The patterns of activity were consistent with known cortical cellular architecture. In a qualitatively different set of experiments, one-photon fluorescence microscopy via voltage-sensitive dyes was successfully employed to image an in vitro preparation of the perfused rat brainstem during the process of respiratory rhythmogenesis. Imaging results yielded insights into the spatial organization of the central respiratory rhythm generation region in the ventrolateral medulla. A multifocal two-photon scanning microscope was constructed, and design and operation principles are described. Utilizing the novel device, anatomical and functional two-photon imaging via potentiometric dyes and calcium dyes is described, and the results of in vivo versus in vitro imaging are compared. Anatomical imaging results used either functional probe background fluorescence or green fluorescent protein (GFP) expression. Spectroscopic experiments measuring the two

  1. Single-neuron NMDA receptor phenotype influences neuronal rewiring and reintegration following traumatic injury.

    Science.gov (United States)

    Patel, Tapan P; Ventre, Scott C; Geddes-Klein, Donna; Singh, Pallab K; Meaney, David F

    2014-03-19

    Alterations in the activity of neural circuits are a common consequence of traumatic brain injury (TBI), but the relationship between single-neuron properties and the aggregate network behavior is not well understood. We recently reported that the GluN2B-containing NMDA receptors (NMDARs) are key in mediating mechanical forces during TBI, and that TBI produces a complex change in the functional connectivity of neuronal networks. Here, we evaluated whether cell-to-cell heterogeneity in the connectivity and aggregate contribution of GluN2B receptors to [Ca(2+)]i before injury influenced the functional rewiring, spontaneous activity, and network plasticity following injury using primary rat cortical dissociated neurons. We found that the functional connectivity of a neuron to its neighbors, combined with the relative influx of calcium through distinct NMDAR subtypes, together contributed to the individual neuronal response to trauma. Specifically, individual neurons whose [Ca(2+)]i oscillations were largely due to GluN2B NMDAR activation lost many of their functional targets 1 h following injury. In comparison, neurons with large GluN2A contribution or neurons with high functional connectivity both independently protected against injury-induced loss in connectivity. Mechanistically, we found that traumatic injury resulted in increased uncorrelated network activity, an effect linked to reduction of the voltage-sensitive Mg(2+) block of GluN2B-containing NMDARs. This uncorrelated activation of GluN2B subtypes after injury significantly limited the potential for network remodeling in response to a plasticity stimulus. Together, our data suggest that two single-cell characteristics, the aggregate contribution of NMDAR subtypes and the number of functional connections, influence network structure following traumatic injury.

  2. Methods for studying functional interactions among neuronal populations.

    Science.gov (United States)

    Narayanan, Nandakumar S; Laubach, Mark

    2009-01-01

    How do populations of neurons work together to control behavior? To study this issue, our group simultaneously records from populations of neurons across multiple electrodes in multiple brain regions during operant behavior. Here, we describe methods for quantifying the relationship between neuronal population activity and performance of operant behavioral tasks. We describe statistical techniques, based on time- and trial-shuffling, that can establish the significance of correlations between multiple and simultaneously recorded spike trains. Then, we describe several approaches to studying functional interactions between neurons, including principal component analysis, cross-correlation analysis, analyses of rate correlations, and analyses of shared predictive information. Finally, we compare these techniques using a sample data set and discuss how the combined use of these techniques can lead to novel insights regarding neuronal interactions during behavior.

  3. Kappe neurons, a novel population of olfactory sensory neurons

    Science.gov (United States)

    Ahuja, Gaurav; Nia, Shahrzad Bozorg; Zapilko, Veronika; Shiriagin, Vladimir; Kowatschew, Daniel; Oka, Yuichiro; Korsching, Sigrun I.

    2014-02-01

    Perception of olfactory stimuli is mediated by distinct populations of olfactory sensory neurons, each with a characteristic set of morphological as well as functional parameters. Beyond two large populations of ciliated and microvillous neurons, a third population, crypt neurons, has been identified in teleost and cartilaginous fishes. We report here a novel, fourth olfactory sensory neuron population in zebrafish, which we named kappe neurons for their characteristic shape. Kappe neurons are identified by their Go-like immunoreactivity, and show a distinct spatial distribution within the olfactory epithelium, similar to, but significantly different from that of crypt neurons. Furthermore, kappe neurons project to a single identified target glomerulus within the olfactory bulb, mdg5 of the mediodorsal cluster, whereas crypt neurons are known to project exclusively to the mdg2 glomerulus. Kappe neurons are negative for established markers of ciliated, microvillous and crypt neurons, but appear to have microvilli. Kappe neurons constitute the fourth type of olfactory sensory neurons reported in teleost fishes and their existence suggests that encoding of olfactory stimuli may require a higher complexity than hitherto assumed already in the peripheral olfactory system.

  4. Lumping Izhikevich neurons

    Directory of Open Access Journals (Sweden)

    Visser Sid

    2014-12-01

    Full Text Available We present the construction of a planar vector field that yields the firing rate of a bursting Izhikevich neuron can be read out, while leaving the sub-threshold behavior intact. This planar vector field is used to derive lumped formulations of two complex heterogeneous networks of bursting Izhikevich neurons. In both cases, the lumped model is compared with the spiking network. There is excellent agreement in terms of duration and number of action potentials within the bursts, but there is a slight mismatch of the burst frequency. The lumped model accurately accounts for both intrinsic bursting and post inhibitory rebound potentials in the neuron model, features which are absent in prevalent neural mass models.

  5. Stochastic neuron models

    CERN Document Server

    Greenwood, Priscilla E

    2016-01-01

    This book describes a large number of open problems in the theory of stochastic neural systems, with the aim of enticing probabilists to work on them. This includes problems arising from stochastic models of individual neurons as well as those arising from stochastic models of the activities of small and large networks of interconnected neurons. The necessary neuroscience background to these problems is outlined within the text, so readers can grasp the context in which they arise. This book will be useful for graduate students and instructors providing material and references for applying probability to stochastic neuron modeling. Methods and results are presented, but the emphasis is on questions where additional stochastic analysis may contribute neuroscience insight. An extensive bibliography is included. Dr. Priscilla E. Greenwood is a Professor Emerita in the Department of Mathematics at the University of British Columbia. Dr. Lawrence M. Ward is a Professor in the Department of Psychology and the Brain...

  6. Imaging voltage in neurons

    Science.gov (United States)

    Peterka, Darcy S.; Takahashi, Hiroto; Yuste, Rafael

    2011-01-01

    In the last decades, imaging membrane potential has become a fruitful approach to study neural circuits, especially in invertebrate preparations with large, resilient neurons. At the same time, particularly in mammalian preparations, voltage imaging methods suffer from poor signal to noise and secondary side effects, and they fall short of providing single-cell resolution when imaging of the activity of neuronal populations. As an introduction to these techniques, we briefly review different voltage imaging methods (including organic fluorophores, SHG chromophores, genetic indicators, hybrid, nanoparticles and intrinsic approaches), and illustrate some of their applications to neuronal biophysics and mammalian circuit analysis. We discuss their mechanisms of voltage sensitivity, from reorientation, electrochromic or electro-optical phenomena, to interaction among chromophores or membrane scattering, and highlight their advantages and shortcomings, commenting on the outlook for development of novel voltage imaging methods. PMID:21220095

  7. Glutamate gated spiking Neuron Model.

    Science.gov (United States)

    Deka, Krisha M; Roy, Soumik

    2014-01-01

    Biological neuron models mainly analyze the behavior of neural networks. Neurons are described in terms of firing rates viz an analog signal. The Izhikevich neuron model is an efficient, powerful model of spiking neuron. This model is a reduction of Hodgkin-Huxley model to a two variable system and is capable of producing rich firing patterns for many biological neurons. In this paper, the Regular Spiking (RS) neuron firing pattern is used to simulate the spiking of Glutamate gated postsynaptic membrane. Simulation is done in MATLAB environment for excitatory action of synapses. Analogous simulation of spiking of excitatory postsynaptic membrane potential is obtained.

  8. Photosensitive neurons in mollusks

    Directory of Open Access Journals (Sweden)

    Kartelija Gordana

    2005-01-01

    Full Text Available In addition to regular photoreceptors, some invertebrates possess simple extra ocular photoreceptors. For ex­ample, the central ganglia of mollusks contain photosensitive neurons. These neurons are located on the dorsal surface of the ganglia and based on their electrophysiological properties it has been postulated that they are internal photoreceptors. Besides the eye, transduction of light also occurs in these extra-ocular photoreceptors. In the present work, we analyze the reactivity of these nerve cells to light and describe the underlying mechanism mediating the light-induced response.

  9. From Neurons to Newtons

    DEFF Research Database (Denmark)

    Nielsen, Bjørn Gilbert

    2001-01-01

    proteins generate forces, to the macroscopic levels where overt arm movements are vol- untarily controlled within an unpredictable environment by legions of neurons¯ring in orderly fashion. An extensive computer simulation system has been developed for this thesis, which at present contains a neural...... network scripting language for specifying arbitrary neural architectures, de¯nition ¯les for detailed spinal networks, various biologically realistic models of neurons, and dynamic synapses. Also included are structurally accurate models of intrafusal and extra-fusal muscle ¯bers and a general body...

  10. Neuronal survival in the brain: neuron type-specific mechanisms

    DEFF Research Database (Denmark)

    Pfisterer, Ulrich Gottfried; Khodosevich, Konstantin

    2017-01-01

    numbers of neurons that are not yet completely integrated into the local circuits helps to ensure that maturation and homeostatic function of neuronal networks in the brain proceed correctly. External signals from brain microenvironment together with intrinsic signaling pathways determine whether......Neurogenic regions of mammalian brain produce many more neurons that will eventually survive and reach a mature stage. Developmental cell death affects both embryonically produced immature neurons and those immature neurons that are generated in regions of adult neurogenesis. Removal of substantial...... a particular neuron will die. To accommodate this signaling, immature neurons in the brain express a number of transmembrane factors as well as intracellular signaling molecules that will regulate the cell survival/death decision, and many of these factors cease being expressed upon neuronal maturation...

  11. Neuronal survival in the brain: neuron type-specific mechanisms

    DEFF Research Database (Denmark)

    Pfisterer, Ulrich Gottfried; Khodosevich, Konstantin

    2017-01-01

    Neurogenic regions of mammalian brain produce many more neurons that will eventually survive and reach a mature stage. Developmental cell death affects both embryonically produced immature neurons and those immature neurons that are generated in regions of adult neurogenesis. Removal of substantial...... numbers of neurons that are not yet completely integrated into the local circuits helps to ensure that maturation and homeostatic function of neuronal networks in the brain proceed correctly. External signals from brain microenvironment together with intrinsic signaling pathways determine whether...... a particular neuron will die. To accommodate this signaling, immature neurons in the brain express a number of transmembrane factors as well as intracellular signaling molecules that will regulate the cell survival/death decision, and many of these factors cease being expressed upon neuronal maturation...

  12. Establishing Communication between Neuronal Populations through Competitive Entrainment.

    Science.gov (United States)

    Wildie, Mark; Shanahan, Murray

    2011-01-01

    The role of gamma frequency oscillation in neuronal interaction, and the relationship between oscillation and information transfer between neurons, has been the focus of much recent research. While the biological mechanisms responsible for gamma oscillation and the properties of resulting networks are well studied, the dynamics of changing phase coherence between oscillating neuronal populations are not well understood. To this end we develop a computational model of competitive selection between multiple stimuli, where the selection and transfer of population-encoded information arises from competition between converging stimuli to entrain a target population of neurons. Oscillation is generated by Pyramidal-Interneuronal Network Gamma through the action of recurrent synaptic connections between a locally connected network of excitatory and inhibitory neurons. Competition between stimuli is driven by differences in coherence of oscillation, while transmission of a single selected stimulus is enabled between generating and receiving neurons via Communication-through-Coherence. We explore the effect of varying synaptic parameters on the competitive transmission of stimuli over different neuron models, and identify a continuous region within the parameter space of the recurrent synaptic loop where inhibition-induced oscillation results in entrainment of target neurons. Within this optimal region we find that competition between stimuli of equal coherence results in model output that alternates between representation of the stimuli, in a manner strongly resembling well-known biological phenomena resulting from competitive stimulus selection such as binocular rivalry.

  13. Lumping Izhikevich neurons

    NARCIS (Netherlands)

    Visser, S.; van Gils, Stephanus A.

    2014-01-01

    We present the construction of a planar vector field that yields the firing rate of a bursting Izhikevich neuron can be read out, while leaving the sub-threshold behaviour intact. This planar vector field is used to derive lumped formulations of two complex heterogeneous networks of bursting

  14. Topographical and quantitative distribution of the projecting neurons to main divisions of the septal area.

    Science.gov (United States)

    Haghdoost-Yazdi, H; Pasbakhsh, P; Vatanparast, J; Rajaei, F; Behzadi, G

    2009-06-01

    Septal area is a limbic structure that is involved in the regulation of several autonomic, learning-related and behavioral functions. Participation of this area in various physiologic functions is indicative of its extensive connections with different brain areas. It contains two major divisions: lateral septum (LS) and medial septum/diagonal band of Broca (MS/DBB). In the present work, we examined topographical distribution of projecting neurons to these divisions and quantitatively verified them. Horseradish peroxidase (HRP) retrograde tract tracing was performed. Our results show that about two-thirds of projections to the septal area terminate in the LS. They mostly originate ipsilaterally from the septal area itself (8%), hippocampal formation (38%), non-specific thalamic nuclei (23%), lateral pre-optic area, lateral hypothalamus, perifornical area and mammillary complex in hypothalamus (20%), ventral tegmental area, raphe and tegmental nuclei, and also locus coeruleus in brainstem (10%). Most afferents to the MS come ipsilaterally from the septal area itself (18%), hippocampal formation (12%), lateral pre-optic area, lateral hypothalamus and mammillary complex in hypothalamus (42%), ventral tegmental area, raphe and tegmental nuclei, central gray matter and also locus coeruleus in brainstem (20%). Some afferents to the septal area originate contralaterally from the lateral hypothalamus, supramammillary area, raphe nuclei and locus coeruleus. Afferents from the interanterodorsal and mediodorsal thalamic nuclei, which increase the role of the septal area in arousal and awareness, are reported for the first time. Projecting cells to the MS support the learning-related function of this area. Projecting cells to the LS that are more scattered throughout the brain indicate its involvement in more diverse functions.

  15. Spiking neuron network Helmholtz machine

    National Research Council Canada - National Science Library

    Sountsov, Pavel; Miller, Paul

    2015-01-01

    .... This paper aims to unify the two fields of probabilistic inference and synaptic plasticity by using a neuronal network of realistic model spiking neurons to implement a well-studied computational...

  16. Identifying neuronal oscillations using rhythmicity

    NARCIS (Netherlands)

    Fransen, A.M.M.; Ede, F.L. van; Maris, E.G.G.

    2015-01-01

    Neuronal oscillations are a characteristic feature of neuronal activity and are typically investigated through measures of power and coherence. However, neither of these measures directly reflects the distinctive feature of oscillations: their rhythmicity. Rhythmicity is the extent to which future

  17. Central thalamic deep brain stimulation to promote recovery from chronic posttraumatic minimally conscious state: challenges and opportunities.

    Science.gov (United States)

    Giacino, Joseph; Fins, Joseph J; Machado, Andre; Schiff, Nicholas D

    2012-07-01

    Central thalamic deep brain stimulation (CT-DBS) may have therapeutic potential to improve behavioral functioning in patients with severe traumatic brain injury (TBI), but its use remains experimental. Current research suggests that the central thalamus plays a critical role in modulating arousal during tasks requiring sustained attention, working memory, and motor function. The aim of the current article is to review the methodology used in the CT-DBS protocol developed by our group, outline the challenges we encountered and offer suggestions for future DBS trials in this population. RATIONAL FOR CT-DBS IN TBI:  CT-DBS may therefore be able to stimulate these functions by eliciting action potentials that excite thalamocortical and thalamostriatal pathways. Because patients in chronic minimally conscious state (MCS) have a very low probability of regaining functional independence, yet often have significant sparing of cortical connectivity, they may represent a particularly appropriate target group for CT-DBS. PIlOT STUDY RESULTS:  We have conducted a series of single-subject studies of CT-DBS in patients with chronic posttraumatic MCS, with 24-month follow-up. Outcomes were measured using the Coma Recovery Scale-Revised as well as a battery of secondary outcome measures to capture more granular changes. Findings from our index case suggest that CT-DBS can significantly increase functional communication, motor performance, feeding, and object naming in the DBS on state, with performance in some domains remaining above baseline even after DBS was turned off. The use of CT-DBS in patients in MCS, however, presents challenges at almost every step, including during surgical planning, outcome measurement, and postoperative care. Additionally, given the difficulties of obtaining informed consent from patients in MCS and the experimental nature of the treatment, a robust, scientifically rooted ethical framework is resented for pursuing this line of work. © 2012

  18. Elastic and viscoelastic mechanical properties of brain tissues on the implanting trajectory of sub-thalamic nucleus stimulation.

    Science.gov (United States)

    Li, Yan; Deng, Jianxin; Zhou, Jun; Li, Xueen

    2016-11-01

    Corresponding to pre-puncture and post-puncture insertion, elastic and viscoelastic mechanical properties of brain tissues on the implanting trajectory of sub-thalamic nucleus stimulation are investigated, respectively. Elastic mechanical properties in pre-puncture are investigated through pre-puncture needle insertion experiments using whole porcine brains. A linear polynomial and a second order polynomial are fitted to the average insertion force in pre-puncture. The Young's modulus in pre-puncture is calculated from the slope of the two fittings. Viscoelastic mechanical properties of brain tissues in post-puncture insertion are investigated through indentation stress relaxation tests for six interested regions along a planned trajectory. A linear viscoelastic model with a Prony series approximation is fitted to the average load trace of each region using Boltzmann hereditary integral. Shear relaxation moduli of each region are calculated using the parameters of the Prony series approximation. The results show that, in pre-puncture insertion, needle force almost increases linearly with needle displacement. Both fitting lines can perfectly fit the average insertion force. The Young's moduli calculated from the slope of the two fittings are worthy of trust to model linearly or nonlinearly instantaneous elastic responses of brain tissues, respectively. In post-puncture insertion, both region and time significantly affect the viscoelastic behaviors. Six tested regions can be classified into three categories in stiffness. Shear relaxation moduli decay dramatically in short time scales but equilibrium is never truly achieved. The regional and temporal viscoelastic mechanical properties in post-puncture insertion are valuable for guiding probe insertion into each region on the implanting trajectory.

  19. Divergent Structural Responses to Pharmacological Interventions in Orbitofronto-Striato-Thalamic and Premotor Circuits in Obsessive-Compulsive Disorder

    Directory of Open Access Journals (Sweden)

    Qiming Lv

    2017-08-01

    Full Text Available Prior efforts to dissect etiological and pharmacological modulations in brain morphology in obsessive-compulsive disorder (OCD are often undermined by methodological and sampling constraints, yielding conflicting conclusions and no reliable neuromarkers. Here we evaluated alteration of regional gray matter volume including effect size (Cohen's d value in 95 drug-naïve patients (age range: 18–55 compared to 95 healthy subjects (age: 18–63, then examined pharmacological effects in 65 medicated (age: 18–57 and 73 medication-free patients (age: 18–61. Robustness of statistical outcomes and effect sizes was rigorously tested with Monte Carlo cross-validation. Relative to controls, both drug-naïve and medication-free patients exhibited comparable volumetric increases mainly in the left thalamus (d = 0.90, 0.82, respectively, left ventral striatum (d = 0.88, 0.67, bilateral medial orbitofrontal cortex (d = 0.86, 0.71; 0.90, 0.73, and left inferior temporal gyrus (d = 0.83, 0.66, and decreased volumes in left premotor/presupplementary motor areas (d = −0.83, −0.71. Interestingly, abnormalities in the thalamus and medial orbitofrontal cortex were present in medicated patients whereas entirely absent in premotor and ventral striatum. It suggests that pharmacotherapy elicited divergent responses in orbitofronto-striato-thalamic and premotor circuits, which warrants the design of longitudinal studies investigating the potential of these neuromarkers in stratified treatments of OCD.

  20. Role of the thalamic nucleus reuniens in mediating interactions between the hippocampus and medial prefrontal cortex during spatial working memory

    Directory of Open Access Journals (Sweden)

    Amy L Griffin

    2015-03-01

    Full Text Available Despite decades of research, the neural mechanisms of spatial working memory remain poorly understood. Although the dorsal hippocampus is known to be critical for memory-guided behavior, experimental evidence suggests that spatial working memory depends not only on the hippocampus itself, but also on the circuit comprised of the hippocampus and the medial prefrontal cortex (mPFC. Disruption of hippocampal-mPFC interactions may result in failed transfer of spatial and contextual information processed by the hippocampus to the circuitry in mPFC responsible for decision making and goal-directed behavior. Oscillatory synchrony between the hippocampus and mPFC has been shown to increase in tasks with high spatial working memory demand. However, the mechanisms and circuitry supporting hippocampal-mPFC interactions during these tasks is unknown. The midline thalamic nucleus reuniens (RE is reciprocally connected to both the hippocampus and the mPFC and has been shown to be critical for a variety of working memory tasks. Therefore, it is likely that hippocampal-mPFC oscillatory synchrony is modulated by RE activity. This article will review the anatomical connections between the hippocampus, mPFC and RE along with the behavioral studies that have investigated the effects of RE disruption on working memory task performance. The article will conclude with suggestions for future directions aimed at identifying the specific role of the RE in regulating functional interactions between the hippocampus and the PFC and investigating the degree to which these interactions contribute to spatial working memory.

  1. Motor neuron disease in blacks

    African Journals Online (AJOL)

    1989-08-19

    Aug 19, 1989 ... We reported earlier that motor neuron disease occurs more commonly among blacks than Parkinson's disease, which is relatively rare in this race group.! The hypothesis that these conditions, and other neuronal abiotrophies, are the result of previous subclinical neuronal insult and subsequent age-related.

  2. Simple model of spiking neurons.

    Science.gov (United States)

    Izhikevich, E M

    2003-01-01

    A model is presented that reproduces spiking and bursting behavior of known types of cortical neurons. The model combines the biologically plausibility of Hodgkin-Huxley-type dynamics and the computational efficiency of integrate-and-fire neurons. Using this model, one can simulate tens of thousands of spiking cortical neurons in real time (1 ms resolution) using a desktop PC.

  3. Moving Neurons back into place

    OpenAIRE

    Kerjan, Geraldine; Gleeson, Joseph G.

    2009-01-01

    Subcortical band heterotopia (SBH) is a neuron migration disorder characterized by an aberrant ‘band-like’ accumulation of neurons within the neocortical white matter, frequently leading to mental retardation and epilepsy. SBH can now be regressed by reactivating neuronal migration.

  4. Neuronal substrate of eating disorders

    OpenAIRE

    Timofeeva, Elena; Calvez, Juliane

    2014-01-01

    Eating disorders are devastating and life-threatening psychiatric diseases. Although clinical and experimental investigations have significantly progressed in discovering the neuronal causes of eating disorders, the exact neuronal and molecular mechanisms of the development and maintenance of these pathologies are not fully understood. The complexity of the neuronal substrate of eating disorders hampers progress in revealing the precise mechanisms. The present re...

  5. Understanding Neuronal Mechanisms of Epilepsy ...

    Indian Academy of Sciences (India)

    Admin

    Control il ti. Human brain. Control epileptic. Mutani et al., 1994 ... of Calcium Transients Evoked in. Response to Spontaneous Epileptic ... Proof : Feed forward inhibition in subiculum. CA1. Subiculum. Stimulation artifact. -60 mV. Excitatory neuron. Inhibitory neuron. Excitatory neuron. Excitatory. Synapse. Inhibitory. Synapse.

  6. Vasculo-Neuronal Coupling: Retrograde Vascular Communication to Brain Neurons.

    Science.gov (United States)

    Kim, Ki Jung; Ramiro Diaz, Juan; Iddings, Jennifer A; Filosa, Jessica A

    2016-12-14

    Continuous cerebral blood flow is essential for neuronal survival, but whether vascular tone influences resting neuronal function is not known. Using a multidisciplinary approach in both rat and mice brain slices, we determined whether flow/pressure-evoked increases or decreases in parenchymal arteriole vascular tone, which result in arteriole constriction and dilation, respectively, altered resting cortical pyramidal neuron activity. We present evidence for intercellular communication in the brain involving a flow of information from vessel to astrocyte to neuron, a direction opposite to that of classic neurovascular coupling and referred to here as vasculo-neuronal coupling (VNC). Flow/pressure increases within parenchymal arterioles increased vascular tone and simultaneously decreased resting pyramidal neuron firing activity. On the other hand, flow/pressure decreases evoke parenchymal arteriole dilation and increased resting pyramidal neuron firing activity. In GLAST-CreERT2; R26-lsl-GCaMP3 mice, we demonstrate that increased parenchymal arteriole tone significantly increased intracellular calcium in perivascular astrocyte processes, the onset of astrocyte calcium changes preceded the inhibition of cortical pyramidal neuronal firing activity. During increases in parenchymal arteriole tone, the pyramidal neuron response was unaffected by blockers of nitric oxide, GABAA, glutamate, or ecto-ATPase. However, VNC was abrogated by TRPV4 channel, GABAB, as well as an adenosine A1 receptor blocker. Differently to pyramidal neuron responses, increases in flow/pressure within parenchymal arterioles increased the firing activity of a subtype of interneuron. Together, these data suggest that VNC is a complex constitutive active process that enables neurons to efficiently adjust their resting activity according to brain perfusion levels, thus safeguarding cellular homeostasis by preventing mismatches between energy supply and demand. We present evidence for vessel-to-neuron

  7. Relationship between the mechanisms of gamma rhythm generation and the magnitude of the macroscopic phase response function in a population of excitatory and inhibitory modified quadratic integrate-and-fire neurons

    Science.gov (United States)

    Akao, Akihiko; Ogawa, Yutaro; Jimbo, Yasuhiko; Ermentrout, G. Bard; Kotani, Kiyoshi

    2018-01-01

    Gamma oscillations are thought to play an important role in brain function. Interneuron gamma (ING) and pyramidal interneuron gamma (PING) mechanisms have been proposed as generation mechanisms for these oscillations. However, the relation between the generation mechanisms and the dynamical properties of the gamma oscillation are still unclear. Among the dynamical properties of the gamma oscillation, the phase response function (PRF) is important because it encodes the response of the oscillation to inputs. Recently, the PRF for an inhibitory population of modified theta neurons that generate an ING rhythm was computed by the adjoint method applied to the associated Fokker-Planck equation (FPE) for the model. The modified theta model incorporates conductance-based synapses as well as the voltage and current dynamics. Here, we extended this previous work by creating an excitatory-inhibitory (E-I) network using the modified theta model and described the population dynamics with the corresponding FPE. We conducted a bifurcation analysis of the FPE to find parameter regions which generate gamma oscillations. In order to label the oscillatory parameter regions by their generation mechanisms, we defined ING- and PING-type gamma oscillation in a mathematically plausible way based on the driver of the inhibitory population. We labeled the oscillatory parameter regions by these generation mechanisms and derived PRFs via the adjoint method on the FPE in order to investigate the differences in the responses of each type of oscillation to inputs. PRFs for PING and ING mechanisms are derived and compared. We found the amplitude of the PRF for the excitatory population is larger in the PING case than in the ING case. Finally, the E-I population of the modified theta neuron enabled us to analyze the PRFs of PING-type gamma oscillation and the entrainment ability of E and I populations. We found a parameter region in which PRFs of E and I are both purely positive in the case of

  8. Visualizing the spinal neuronal dynamics of locomotion

    Science.gov (United States)

    Subramanian, Kalpathi R.; Bashor, D. P.; Miller, M. T.; Foster, J. A.

    2004-06-01

    Modern imaging and simulation techniques have enhanced system-level understanding of neural function. In this article, we present an application of interactive visualization to understanding neuronal dynamics causing locomotion of a single hip joint, based on pattern generator output of the spinal cord. Our earlier work visualized cell-level responses of multiple neuronal populations. However, the spatial relationships were abstract, making communication with colleagues difficult. We propose two approaches to overcome this: (1) building a 3D anatomical model of the spinal cord with neurons distributed inside, animated by the simulation and (2) adding limb movements predicted by neuronal activity. The new system was tested using a cat walking central pattern generator driving a pair of opposed spinal motoneuron pools. Output of opposing motoneuron pools was combined into a single metric, called "Net Neural Drive", which generated angular limb movement in proportion to its magnitude. Net neural drive constitutes a new description of limb movement control. The combination of spatial and temporal information in the visualizations elegantly conveys the neural activity of the output elements (motoneurons), as well as the resulting movement. The new system encompasses five biological levels of organization from ion channels to observed behavior. The system is easily scalable, and provides an efficient interactive platform for rapid hypothesis testing.

  9. The role of the thalamic nuclei in recognition memory accompanied by recall during encoding and retrieval: an fMRI study.

    Science.gov (United States)

    Pergola, Giulio; Ranft, Alexander; Mathias, Klaus; Suchan, Boris

    2013-07-01

    The present functional imaging study aimed at investigating the contribution of the mediodorsal nucleus and the anterior nuclei of the thalamus with their related cortical networks to recognition memory and recall. Eighteen subjects performed associative picture encoding followed by a single item recognition test during the functional magnetic resonance imaging session. After scanning, subjects performed a cued recall test using the formerly recognized pictures as cues. This post-scanning test served to classify recognition trials according to subsequent recall performance. In general, single item recognition accompanied by successful recall of the associations elicited stronger activation in the mediodorsal nucleus of the thalamus and in the prefrontal cortices both during encoding and retrieval compared to recognition without recall. In contrast, the anterior nuclei of the thalamus were selectively active during the retrieval phase of recognition followed by recall. A correlational analysis showed that activation of the anterior thalamus during retrieval as assessed by measuring the percent signal changes predicted lower rates of recognition without recall. These findings show that the thalamus is critical for recognition accompanied by recall, and provide the first evidence of a functional segregation of the thalamic nuclei with respect to the memory retrieval phase. In particular, the mediodorsal thalamic-prefrontal cortical network is activated during successful encoding and retrieval of associations, which suggests a role of this system in recall and recollection. The activity of the anterior thalamic-temporal network selectively during retrieval predicts better memory performances across subjects and this confirms the paramount role of this network in recall and recollection. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. A mechanism for cognitive dynamics: neuronal communication through neuronal coherence.

    Science.gov (United States)

    Fries, Pascal

    2005-10-01

    At any one moment, many neuronal groups in our brain are active. Microelectrode recordings have characterized the activation of single neurons and fMRI has unveiled brain-wide activation patterns. Now it is time to understand how the many active neuronal groups interact with each other and how their communication is flexibly modulated to bring about our cognitive dynamics. I hypothesize that neuronal communication is mechanistically subserved by neuronal coherence. Activated neuronal groups oscillate and thereby undergo rhythmic excitability fluctuations that produce temporal windows for communication. Only coherently oscillating neuronal groups can interact effectively, because their communication windows for input and for output are open at the same times. Thus, a flexible pattern of coherence defines a flexible communication structure, which subserves our cognitive flexibility.

  11. Electrophysiological study of supraspinal input and spinal output of cat's subnucleus reticularis dorsalis (SRD neurons.

    Directory of Open Access Journals (Sweden)

    Patricia Velo

    Full Text Available This work addressed the study of subnucleus reticularis dorsalis (SRD neurons in relation to their supraspinal input and the spinal terminating sites of their descending axons. SRD extracellular unitary recordings from anesthetized cats aimed to specifically test, 1 the rostrocaudal segmental level reached by axons of spinally projecting (SPr neurons collateralizing or not to or through the ipsilateral nucleus reticularis gigantocellularis (NRGc, 2 whether SPr fibers bifurcate to the thalamus, and 3 the effects exerted on SRD cells by electrically stimulating the locus coeruleus, the periaqueductal grey, the nucleus raphe magnus, and the mesencephalic locomotor region. From a total of 191 SPr fibers tested to cervical 2 (Ce2, thoracic 5 (Th5 and lumbar5 (Lu5 stimulation, 81 ended between Ce2 and Th5 with 39 of them branching to or through the NRGc; 21/49 terminating between Th5 and Lu5 collateralized to or through the same nucleus, as did 34/61 reaching Lu5. The mean antidromic conduction velocity of SPr fibers slowed in the more proximal segments and increased with terminating distance along the cord. None of the 110 axons tested sent collaterals to the thalamus; instead thalamic stimulation induced long-latency polysynaptic responses in most cells but also short-latency, presumed monosynaptic, in 7.9% of the tested neurons (18/227. Antidromic and orthodromic spikes were elicited from the locus coeruleus and nucleus raphe magnus, but exclusively orthodromic responses were observed following stimulation of the periaqueductal gray or mesencephalic locomotor region. The results suggest that information from pain-and-motor-related supraspinal structures converge on SRD cells that through SPr axons having conduction velocities tuned to their length may affect rostral and caudal spinal cord neurons at fixed delays, both directly and in parallel through different descending systems. The SRD will thus play a dual functional role by simultaneously

  12. Using a hybrid neuron in physiologically inspired models of the basal ganglia

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    Corey Michael Thibeault

    2013-07-01

    Full Text Available Our current understanding of the basal ganglia has facilitated the creation of computational models that have contributed novel theories, explored new functional anatomy and demonstrated results complementing physiological experiments. However, the utility of these models extends beyond these applications. Particularly in neuromorphic engineering, where the basal ganglia's role in computation is important for applications such as power efficient autonomous agents and model-based control strategies. The neurons used in existing computational models of the basal ganglia however, are not amenable for many low-power hardware implementations. Motivated by a need for more hardware accessible networks, we replicate four published models of the basal ganglia, spanning single neuron and small networks, replacing the more computationally expensive neuron models with an Izhikevich hybrid neuron. This begins with a network modeling action-selection, where the basal activity levels and the ability to appropriately select the most salient input is reproduced. A Parkinson's disease model is then explored under normal conditions, Parkinsonian conditions and during subthalamic nucleus deep brain stimulation. The resulting network is capable of replicating the loss of thalamic relay capabilities in the Parkinsonian state and its return under deep brain stimulation. This is also demonstrated using a network capable of action-selection. Finally, a study of correlation transfer under different patterns of Parkinsonian activity is presented. These networks successfully captured the significant results of the originals studies. This not only creates a foundation for neuromorphic hardware implementations but may also support the development of large-scale biophysical models. The former potentially providing a way of improving the efficacy of deep brain stimulation and the latter allowing for the efficient simulation of larger more comprehensive networks.

  13. Using a hybrid neuron in physiologically inspired models of the basal ganglia.

    Science.gov (United States)

    Thibeault, Corey M; Srinivasa, Narayan

    2013-01-01

    Our current understanding of the basal ganglia (BG) has facilitated the creation of computational models that have contributed novel theories, explored new functional anatomy and demonstrated results complementing physiological experiments. However, the utility of these models extends beyond these applications. Particularly in neuromorphic engineering, where the basal ganglia's role in computation is important for applications such as power efficient autonomous agents and model-based control strategies. The neurons used in existing computational models of the BG, however, are not amenable for many low-power hardware implementations. Motivated by a need for more hardware accessible networks, we replicate four published models of the BG, spanning single neuron and small networks, replacing the more computationally expensive neuron models with an Izhikevich hybrid neuron. This begins with a network modeling action-selection, where the basal activity levels and the ability to appropriately select the most salient input is reproduced. A Parkinson's disease model is then explored under normal conditions, Parkinsonian conditions and during subthalamic nucleus deep brain stimulation (DBS). The resulting network is capable of replicating the loss of thalamic relay capabilities in the Parkinsonian state and its return under DBS. This is also demonstrated using a network capable of action-selection. Finally, a study of correlation transfer under different patterns of Parkinsonian activity is presented. These networks successfully captured the significant results of the originals studies. This not only creates a foundation for neuromorphic hardware implementations but may also support the development of large-scale biophysical models. The former potentially providing a way of improving the efficacy of DBS and the latter allowing for the efficient simulation of larger more comprehensive networks.

  14. State-dependency of neuronal slow dynamics during sleep observed in cat lateral geniculate nucleus.

    Science.gov (United States)

    Nakamura, K; Yamamoto, M; Takahashi, K; Nakao, M; Mizutani, Y; Katayama, N; Kodama, T

    2000-01-01

    From the accumulated results, we hypothesize that neurons in the central processor systems of the brain generally exhibit a common state-dependency in slow dynamics of their spontaneous activities during sleep. In this paper, activities of relay cells in the cat's lateral geniculate nucleus (LGN) were studied to see if our hypothesis can be applied in this thalamic region. Data segments in polygraphically steady states were strictly extracted in order to sample the activities whose stationarity was guaranteed in a statistical sense. During slow wave sleep (SWS), the discharge pattern was characterized by short bursts. In contrast, the rather tonic discharge pattern was observed to prevail during rapid eye movement (REM) sleep. Spectral analyses showed white noise-like spectra in the low frequency range of 0.04-1.0 Hz during SWS, and 1/f noise-like spectra in the same frequency range during REM sleep. This state-dependency of the slow dynamics was consistently characterized by the other statistical parameters concerning the second-order moment as well. In contrast, the fast dynamics over 1.0 Hz tended to exhibit neuron-specific changes associated with the sleep state in terms of the Markovian dependency analysis. Consequently, our working hypothesis was not rejected for the LGN relay cells. The result here extends the possibility that the state-dependency of the slow dynamics we found is a general rule concerning single neuronal dynamics in widespread areas of the brain during sleep. The state-dependency of the slow dynamics of the LGN relay cells could be understood according to the proposed mechanism that a state-associated alteration in the global biasing input to a neural network during sleep induces the phenomenon with which we are concerned. The slow dynamics of neuronal activities might provide a novel framework defining SWS and REM sleep states instead of the polygraphic characteristics.

  15. Cytoreductive Surgery Followed by Hyperthermic Intraperitoneal Chemotherapy for Recurrent Ovarian Cancer with Incidental Bochdalek Hernia and Postoperative Bilateral Thalamic Infarct: A Case Report

    Directory of Open Access Journals (Sweden)

    Ilker Kahramanoglu

    2017-03-01

    Full Text Available Congenital Bochdalek hernia is a defect of the diaphragm and very rare in adults. Only around 100 cases have been reported in the literature. Herein, we present a case with a recurrent ovarian cancer who underwent secondary cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. An oval defect with dimensions of 3 × 4 cm was seen in the left posterolateral site of the diaphragm during surgical exploration. In addition, a 6 × 3 cm iatrogenic right-sided diaphragmatic defect was found and repaired. In the early postoperative period, a bilateral thalamic infarction occurred.

  16. Cytoreductive Surgery Followed by Hyperthermic Intraperitoneal Chemotherapy for Recurrent Ovarian Cancer with Incidental Bochdalek Hernia and Postoperative Bilateral Thalamic Infarct: A Case Report.

    Science.gov (United States)

    Kahramanoglu, Ilker; Turan, Hasan; Yamak Altinpulluk, Ece; Mammadov, Zahid; Bese, Tugan; Arvas, Macit; Demirkiran, Fuat

    2017-01-01

    Congenital Bochdalek hernia is a defect of the diaphragm and very rare in adults. Only around 100 cases have been reported in the literature. Herein, we present a case with a recurrent ovarian cancer who underwent secondary cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. An oval defect with dimensions of 3 × 4 cm was seen in the left posterolateral site of the diaphragm during surgical exploration. In addition, a 6 × 3 cm iatrogenic right-sided diaphragmatic defect was found and repaired. In the early postoperative period, a bilateral thalamic infarction occurred.

  17. Connectivity and dynamics of neuronal networks as defined by the shape of individual neurons

    Science.gov (United States)

    Ahnert, Sebastian E.; Travençolo, Bruno A. N.; da Fontoura Costa, Luciano

    2009-10-01

    Biological neuronal networks constitute a special class of dynamical systems, as they are formed by individual geometrical components, namely the neurons. In the existing literature, relatively little attention has been given to the influence of neuron shape on the overall connectivity and dynamics of the emerging networks. The current work addresses this issue by considering simplified neuronal shapes consisting of circular regions (soma/axons) with spokes (dendrites). Networks are grown by placing these patterns randomly in the two-dimensional (2D) plane and establishing connections whenever a piece of dendrite falls inside an axon. Several topological and dynamical properties of the resulting graph are measured, including the degree distribution, clustering coefficients, symmetry of connections, size of the largest connected component, as well as three hierarchical measurements of the local topology. By varying the number of processes of the individual basic patterns, we can quantify relationships between the individual neuronal shape and the topological and dynamical features of the networks. Integrate-and-fire dynamics on these networks is also investigated with respect to transient activation from a source node, indicating that long-range connections play an important role in the propagation of avalanches.

  18. Connectivity and dynamics of neuronal networks as defined by the shape of individual neurons

    Energy Technology Data Exchange (ETDEWEB)

    Ahnert, Sebastian E [Theory of Condensed Matter, Cavendish Laboratory, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE (United Kingdom); A N Travencolo, Bruno; Costa, Luciano da Fontoura [Instituto de FIsica de Sao Carlos, Universidade de Sao Paulo, Av. Trabalhador Sao Carlense 400, Caixa Postal 369, CEP 13560-970, Sao Carlos, Sao Paulo (Brazil)], E-mail: luciano@if.sc.usp.br

    2009-10-15

    Biological neuronal networks constitute a special class of dynamical systems, as they are formed by individual geometrical components, namely the neurons. In the existing literature, relatively little attention has been given to the influence of neuron shape on the overall connectivity and dynamics of the emerging networks. The current work addresses this issue by considering simplified neuronal shapes consisting of circular regions (soma/axons) with spokes (dendrites). Networks are grown by placing these patterns randomly in the two-dimensional (2D) plane and establishing connections whenever a piece of dendrite falls inside an axon. Several topological and dynamical properties of the resulting graph are measured, including the degree distribution, clustering coefficients, symmetry of connections, size of the largest connected component, as well as three hierarchical measurements of the local topology. By varying the number of processes of the individual basic patterns, we can quantify relationships between the individual neuronal shape and the topological and dynamical features of the networks. Integrate-and-fire dynamics on these networks is also investigated with respect to transient activation from a source node, indicating that long-range connections play an important role in the propagation of avalanches.

  19. Ongoing Spontaneous Activity Controls Access to Consciousness: A Neuronal Model for Inattentional Blindness

    Science.gov (United States)

    Changeux, Jean-Pierre

    2005-01-01

    Even in the absence of sensory inputs, cortical and thalamic neurons can show structured patterns of ongoing spontaneous activity, whose origins and functional significance are not well understood. We use computer simulations to explore the conditions under which spontaneous activity emerges from a simplified model of multiple interconnected thalamocortical columns linked by long-range, top-down excitatory axons, and to examine its interactions with stimulus-induced activation. Simulations help characterize two main states of activity. First, spontaneous gamma-band oscillations emerge at a precise threshold controlled by ascending neuromodulator systems. Second, within a spontaneously active network, we observe the sudden “ignition” of one out of many possible coherent states of high-level activity amidst cortical neurons with long-distance projections. During such an ignited state, spontaneous activity can block external sensory processing. We relate those properties to experimental observations on the neural bases of endogenous states of consciousness, and particularly the blocking of access to consciousness that occurs in the psychophysical phenomenon of “inattentional blindness,” in which normal subjects intensely engaged in mental activity fail to notice salient but irrelevant sensory stimuli. Although highly simplified, the generic properties of a minimal network may help clarify some of the basic cerebral phenomena underlying the autonomy of consciousness. PMID:15819609

  20. Looming-sensitive responses and receptive field organization of telencephalic neurons in the pigeon.

    Science.gov (United States)

    Xiao, Qian; Li, Da-Peng; Wang, Shu-Rong

    2006-01-30

    The tectofugal pathway in birds goes from the optic tectum to the telencephalic entopallium via the thalamic nucleus rotundus (nRt). This pathway may be homologous to the colliculo-pulvinar-cortical pathway in mammals. It is known that a population of rotundal neurons in the pigeon can signal impending collision of looming objects with the animal. Here we show by single-unit recording that there exist two groups of looming-sensitive neurons in the entopallium. A tau cell starts firing at a nearly constant time before collision whereas the response onset time of an eta cell is linearly related to the square root of the diameter/velocity ratio of looming objects. These cells are localized in the caudal entopallium. The receptive field (RF) of looming-sensitive cells was mapped on the screen plane but its inhibitory region could not suppress responses to looming objects. It appears that a population of telencephalic cells in pigeons responds to looming objects and their looming responses are not determined by the receptive field organization mapped on the screen plane.

  1. Ongoing spontaneous activity controls access to consciousness: a neuronal model for inattentional blindness.

    Directory of Open Access Journals (Sweden)

    Stanislas Dehaene

    2005-05-01

    Full Text Available Even in the absence of sensory inputs, cortical and thalamic neurons can show structured patterns of ongoing spontaneous activity, whose origins and functional significance are not well understood. We use computer simulations to explore the conditions under which spontaneous activity emerges from a simplified model of multiple interconnected thalamocortical columns linked by long-range, top-down excitatory axons, and to examine its interactions with stimulus-induced activation. Simulations help characterize two main states of activity. First, spontaneous gamma-band oscillations emerge at a precise threshold controlled by ascending neuromodulator systems. Second, within a spontaneously active network, we observe the sudden "ignition" of one out of many possible coherent states of high-level activity amidst cortical neurons with long-distance projections. During such an ignited state, spontaneous activity can block external sensory processing. We relate those properties to experimental observations on the neural bases of endogenous states of consciousness, and particularly the blocking of access to consciousness that occurs in the psychophysical phenomenon of "inattentional blindness," in which normal subjects intensely engaged in mental activity fail to notice salient but irrelevant sensory stimuli. Although highly simplified, the generic properties of a minimal network may help clarify some of the basic cerebral phenomena underlying the autonomy of consciousness.

  2. Spiking in auditory cortex following thalamic stimulation is dominated by cortical network activity

    Science.gov (United States)

    Krause, Bryan M.; Raz, Aeyal; Uhlrich, Daniel J.; Smith, Philip H.; Banks, Matthew I.

    2014-01-01

    The state of the sensory cortical network can have a profound impact on neural responses and perception. In rodent auditory cortex, sensory responses are reported to occur in the context of network events, similar to brief UP states, that produce “packets” of spikes and are associated with synchronized synaptic input (Bathellier et al., 2012; Hromadka et al., 2013; Luczak et al., 2013). However, traditional models based on data from visual and somatosensory cortex predict that ascending sensory thalamocortical (TC) pathways sequentially activate cells in layers 4 (L4), L2/3, and L5. The relationship between these two spatio-temporal activity patterns is unclear. Here, we used calcium imaging and electrophysiological recordings in murine auditory TC brain slices to investigate the laminar response pattern to stimulation of TC afferents. We show that although monosynaptically driven spiking in response to TC afferents occurs, the vast majority of spikes fired following TC stimulation occurs during brief UP states and outside the context of the L4>L2/3>L5 activation sequence. Specifically, monosynaptic subthreshold TC responses with similar latencies were observed throughout layers 2–6, presumably via synapses onto dendritic processes located in L3 and L4. However, monosynaptic spiking was rare, and occurred primarily in L4 and L5 non-pyramidal cells. By contrast, during brief, TC-induced UP states, spiking was dense and occurred primarily in pyramidal cells. These network events always involved infragranular layers, whereas involvement of supragranular layers was variable. During UP states, spike latencies were comparable between infragranular and supragranular cells. These data are consistent with a model in which activation of auditory cortex, especially supragranular layers, depends on internally generated network events that represent a non-linear amplification process, are initiated by infragranular cells and tightly regulated by feed-forward inhibitory

  3. Phosphoinositide signaling in somatosensory neurons

    Science.gov (United States)

    Rohacs, Tibor

    2015-01-01

    Somatosensory neurons of the dorsal root ganglia (DRG) and trigeminal ganglia (TG) are responsible for detecting thermal and tactile stimuli. They are also the primary neurons mediating pain and itch. A large number of cell surface receptors in these neurons couple to phospholipase C (PLC) enzymes leading to the hydrolysis of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and the generation of downstream signaling molecules. These neurons also express many different ion channels, several of which are regulated by phosphoinositides. This review will summarize the knowledge on phosphoinositide signaling in these neurons, with special focus on effects on sensory and other ion channels. PMID:26724974

  4. Neuron-specific splicing.

    Science.gov (United States)

    Hakim, Nor Hakimah Ab; Majlis, Burhanuddin Yeop; Suzuki, Hitoshi; Tsukahara, Toshifumi

    2017-03-22

    During pre-mRNA splicing events, introns are removed from the pre-mRNA, and the remaining exons are connected together to form a single continuous molecule. Alternative splicing is a common mechanism for the regulation of gene expression in eukaryotes. More than 90% of human genes are known to undergo alternative splicing. The most common type of alternative splicing is exon skipping, which is also known as cassette exon. Other known alternative splicing events include alternative 5' splice sites, alternative 3' splice sites, intron retention, and mutually exclusive exons. Alternative splicing events are controlled by regulatory proteins responsible for both positive and negative regulation. In this review, we focus on neuronal splicing regulators and discuss several notable regulators in depth. In addition, we have also included an example of splicing regulation mediated by the RBFox protein family. Lastly, as previous studies have shown that a number of splicing factors are associated with neuronal diseases such as Alzheime's disease (AD) and Autism spectrum disorder (ASD), here we consider their importance in neuronal diseases wherein the underlying mechanisms have yet to be elucidated.

  5. Population Coding in Sparsely Connected Networks of Noisy Neurons

    Directory of Open Access Journals (Sweden)

    Bryan Patrick Tripp

    2012-05-01

    Full Text Available This study examines the relationship between population coding and spatial connection statistics in networks of noisy neurons. Encoding of sensory information in the neocortex is thought to require coordinated neural populations, because individual cortical neurons respond to a wide range of stimuli, and exhibit highly variable spiking in response to repeated stimuli. Population coding is rooted in network structure, because cortical neurons receive information only from other neurons, and because the information they encode must be decoded by other neurons, if it is to affect behaviour. However, population coding theory has often ignored network structure, or assumed discrete, fully-connected populations (in contrast with the sparsely connected, continuous sheet of the cortex. In this study, we model a sheet of cortical neurons with sparse, primarily local connections, and find that a network with this structure can encode multiple internal state variables with high signal-to-noise ratio. However, in our model, although connection probability varies with the distance between neurons, we find that the connections cannot be instantiated at random according to these probabilities, but must have additional structure if information is to be encoded with high fidelity.

  6. Parvalbumin+ Neurons and Npas1+ Neurons Are Distinct Neuron Classes in the Mouse External Globus Pallidus

    Science.gov (United States)

    Hernández, Vivian M.; Hegeman, Daniel J.; Cui, Qiaoling; Kelver, Daniel A.; Fiske, Michael P.; Glajch, Kelly E.; Pitt, Jason E.; Huang, Tina Y.; Justice, Nicholas J.

    2015-01-01

    Compelling evidence suggests that pathological activity of the external globus pallidus (GPe), a nucleus in the basal ganglia, contributes to the motor symptoms of a variety of movement disorders such as Parkinson's disease. Recent studies have challenged the idea that the GPe comprises a single, homogenous population of neurons that serves as a simple relay in the indirect pathway. However, we still lack a full understanding of the diversity of the neurons that make up the GPe. Specifically, a more precise classification scheme is needed to better describe the fundamental biology and function of different GPe neuron classes. To this end, we generated a novel multicistronic BAC (bacterial artificial chromosome) transgenic mouse line under the regulatory elements of the Npas1 gene. Using a combinatorial transgenic and immunohistochemical approach, we discovered that parvalbumin-expressing neurons and Npas1-expressing neurons in the GPe represent two nonoverlapping cell classes, amounting to 55% and 27% of the total GPe neuron population, respectively. These two genetically identified cell classes projected primarily to the subthalamic nucleus and to the striatum, respectively. Additionally, parvalbumin-expressing neurons and Npas1-expressing neurons were distinct in their autonomous and driven firing characteristics, their expression of intrinsic ion conductances, and their responsiveness to chronic 6-hydroxydopamine lesion. In summary, our data argue that parvalbumin-expressing neurons and Npas1-expressing neurons are two distinct functional classes of GPe neurons. This work revises our understanding of the GPe, and provides the foundation for future studies of its function and dysfunction. SIGNIFICANCE STATEMENT Until recently, the heterogeneity of the constituent neurons within the external globus pallidus (GPe) was not fully appreciated. We addressed this knowledge gap by discovering two principal GPe neuron classes, which were identified by their nonoverlapping

  7. Astroglial networks promote neuronal coordination.

    Science.gov (United States)

    Chever, Oana; Dossi, Elena; Pannasch, Ulrike; Derangeon, Mickael; Rouach, Nathalie

    2016-01-12

    Astrocytes interact with neurons to regulate network activity. Although the gap junction subunits connexin 30 and connexin 43 mediate the formation of extensive astroglial networks that cover large functional neuronal territories, their role in neuronal synchronization remains unknown. Using connexin 30- and connexin 43-deficient mice, we showed that astroglial networks promoted sustained population bursts in hippocampal slices by setting the basal active state of neurons. Astroglial networks limited excessive neuronal depolarization induced by spontaneous synaptic activity, increased neuronal release probability, and favored the recruitment of neurons during bursting, thus promoting the coordinated activation of neuronal networks. In vivo, this sustained neuronal coordination translated into increased severity of acutely evoked epileptiform events and convulsive behavior. These results revealed that connexin-mediated astroglial networks synchronize bursting of neuronal assemblies, which can exacerbate pathological network activity and associated behavior. Our data thus provide molecular and biophysical evidence predicting selective astroglial gap junction inhibitors as anticonvulsive drugs. Copyright © 2016, American Association for the Advancement of Science.

  8. Long-term follow-up of anterior thalamic deep brain stimulation in epilepsy: A 11-year, single center experience.

    Science.gov (United States)

    Kim, Seong Hoon; Lim, Sung Chul; Kim, Jiyeon; Son, Byung-Chul; Lee, Kyung Jin; Shon, Young-Min

    2017-10-14

    Anterior thalamic deep brain stimulation (ATN DBS) is an emerging, effective treatment for patients with drug-resistant epilepsy, but long-term results on its efficacy and safety are lacking. To evaluate the long-term efficacy and safety of ATN DBS treatment, as well as predictors of its success, in patients with drug-refractory epilepsy (DRE). We retrospectively studied clinical outcomes in 29 consecutive refractory epilepsy patients treated by a single DBS team (two neurosurgeons, four neurologists) over an 11-year period, for whom follow-up was performed for up to 137 months (mean, 74.9 months). The average participant was 30.7 (±10.4) years old and had epilepsy for 19.3 (±9.0) years. The mean preoperative frequency of disabling partial or generalized tonic-clonic seizures was 27.5 (±8.6, SE) seizures a month. The median percent seizure reduction was 71.3% at 1year, 73.9% at 2 years, and ranged from 61.8% to 80.0% over post-implant years 3 through 11 in the long-term study (overall 70% median reduction). In the 11-year study period, 13.8% (4/29) of subjects were seizure-free for at least 12 months during this time. There was only one symptomatic intracranial hemorrhage that happened during follow-up (3.4%). Infection requiring removal and later re-implantation of hardware occurred in only 1 of 30 patients (3.3%), who was subsequently excluded from our follow-up assessment. Hardware malfunction including lead disconnection occurred in 2 of 29 cases (6.9%). Revision of lead position to redeem poor clinical response was performed in 3 of 58 implanted leads (5.2%). ATN DBS can be an effective therapy in a variety of patients with DRE. Importantly, we provide evidence that significant therapeutic efficacy can be sustained for up to 11 years. Neurological complications were rather rare, but long-term hardware-related complications should be followed arrectis auribus. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  9. Motor neurons and the generation of spinal motor neurons diversity

    OpenAIRE

    Nicolas eStifani

    2014-01-01

    Motor neurons (MNs) are neuronal cells located in the central nervous system (CNS) controlling a variety of downstream targets. This function infers the existence of MN subtypes matching the identity of the targets they innervate. To illustrate the mechanism involved in the generation of cellular diversity and the acquisition of specific identity, this review will focus on spinal motor neurons (SpMNs) that have been the core of significant work and discoveries during the last decades. SpMNs a...

  10. Nasal neuron PET imaging quantifies neuron generation and degeneration

    National Research Council Canada - National Science Library

    Van de Bittner, Genevieve C; Riley, Misha M; Cao, Luxiang; Ehses, Janina; Herrick, Scott P; Ricq, Emily L; Wey, Hsiao-Ying; O'Neill, Michael J; Ahmed, Zeshan; Murray, Tracey K; Smith, Jaclyn E; Wang, Changning; Schroeder, Frederick A; Albers, Mark W; Hooker, Jacob M

    2017-01-01

    .... Quantification of the olfactory sensory neurons (OSNs), which detect odors within the nasal cavity, would provide insight into the etiology of olfactory dysfunction associated with disease and mortality...

  11. Cholinergic Neurons - Keeping Check on Amyloid beta in the Cerebral Cortex

    Directory of Open Access Journals (Sweden)

    Saak V. Ovsepian

    2013-12-01

    Full Text Available The physiological relevance of the uptake of ligands with no apparent trophic functions via the p75 neurotrophin receptor (p75NTR remains unclear. Herein, we propose a homeostatic role for this in clearance of amyloid β (Aβ in the brain. We hypothesize that uptake of Aβ in conjunction with p75NTR followed by its degradation in lysosomes endows cholinergic basalo-cortical projections enriched in this receptor a facility for maintaining physiological levels of Aβ in target areas. Thus, in addition to the diffuse modulator influence and channeling of extra-thalamic signals, cholinergic innervations could supply the cerebral cortex with an elaborate system for Aβ drainage. Interpreting the emerging relationship of new molecular data with established role of cholinergic modulator system in regulating cortical network dynamics should provide new insights into the brain physiology and mechanisms of neuro-degenerative diseases.

  12. Resonate-and-fire neurons.

    Science.gov (United States)

    Izhikevich, E M

    2001-01-01

    We suggest a simple spiking model-resonate-and-fire neuron, which is similar to the integrate-and-fire neuron except that the state variable is complex. The model provides geometric illustrations to many interesting phenomena occurring in biological neurons having subthreshold damped oscillations of membrane potential. For example, such neurons prefer a certain resonant frequency of the input that is nearly equal to their eigenfrequency, they can be excited or inhibited by a doublet (two pulses) depending on its interspike interval, and they can fire in response to an inhibitory input. All these properties could be observed in Hodgkin-Huxley-type models. We use the resonate-and-fire model to illustrate possible sensitivity of biological neurons to the fine temporal structure of the input spike train. Being an analogue of the integrate-and-fire model, the resonate-and-fire model is computationally efficient and suitable for simulations of large networks of spiking neurons.

  13. Subcortical connections of normotopic and heterotopic neurons in sensory and motor cortices of the tish mutant rat.

    Science.gov (United States)

    Schottler, F; Couture, D; Rao, A; Kahn, H; Lee, K S

    1998-05-25

    Orthograde and retrograde tracers were used to examine subcortical connections of neurons in the neurological mutant tish rat. This animal exhibits bilateral heterotopia similar to those observed in epileptic humans with subcortical band heterotopia. Terminal varicosities were labeled in the striatum, thalamus, brainstem, and spinal cord following injections of the anterograde tracer biotinylated dextran amine (BDA) into the heterotopic cortex. The general topography of corticothalamic projections was evaluated by injecting the retrograde tracer Fluoro-Gold (FG) into ventral thalamic nuclei. Retrograde labeling of small-to-medium sized neurons was observed in layer VI of topographically restricted portions of the normotopic cortex. Similar appearing cells were labeled in the neighboring portions of the underlying heterotopia; however, these neurons did not display characteristic lamination or radial orientation. Thalamocortical terminals labeled by injecting BDA into the ventroposterolateral nucleus (VPL) were observed primarily in layer IV of the medial aspect of the normotopic somatosensory cortex. In contrast, a radial column of terminals was present in the underlying heterotopia. Typical barrel labeling was found in the lateral aspect of the normotopic somatosensory cortex after injecting the ventroposteromedial nucleus (VPM), whereas more diffuse patches of labeling were observed in the underlying heterotopia. Heterotopic neurons in the tish cortex, thus, exhibit characteristic features of subcortical connectivity. Both normotopic and heterotopic neurons in the tish brain project to appropriate subcortical sites and establish bidirectional topographic connections with the thalamus. These results suggest that primary sensory-motor information is represented in a parallel manner in the normotopic and heterotopic cortices of the tish rat.

  14. The biophysics of neuronal growth

    Energy Technology Data Exchange (ETDEWEB)

    Franze, Kristian; Guck, Jochen [Cavendish Laboratory, Department of Physics, University of Cambridge, JJ Thomson Avenue, Cambridge, CB3 0HE (United Kingdom)

    2010-09-01

    For a long time, neuroscience has focused on biochemical, molecular biological and electrophysiological aspects of neuronal physiology and pathology. However, there is a growing body of evidence indicating the importance of physical stimuli for neuronal growth and development. In this review we briefly summarize the historical background of neurobiophysics and give an overview over the current understanding of neuronal growth from a physics perspective. We show how biophysics has so far contributed to a better understanding of neuronal growth and discuss current inconsistencies. Finally, we speculate how biophysics may contribute to the successful treatment of lesions to the central nervous system, which have been considered incurable until very recently.

  15. Generation and characterization of transgenic mice expressing mitochondrial targeted red fluorescent protein selectively in neurons: modeling mitochondriopathy in excitotoxicity and amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Wang Yi

    2011-11-01

    Full Text Available Abstract Background Mitochondria have roles or appear to have roles in the pathogenesis of several chronic age-related and acute neurological disorders, including Charcot-Marie-Tooth disease, amyotrophic lateral sclerosis, Parkinson's disease, and cerebral ischemia, and could be critical targets for development of rational mechanism-based, disease-modifying therapeutics for treating these disorders effectively. A deeper understanding of neural tissue mitochondria pathobiologies as definitive mediators of neural injury, disease, and cell death merits further study, and the development of additional tools to study neural mitochondria will help achieve this unmet need. Results We created transgenic mice that express the coral (Discosoma sp. red fluorescent protein DsRed2 specifically in mitochondria of neurons using a construct engineered with a Thy1 promoter, specific for neuron expression, to drive expression of a fusion protein of DsRed2 with a mitochondrial targeting sequence. The biochemical and histological characterization of these mice shows the expression of mitochondrial-targeted DsRed2 to be specific for mitochondria and concentrated in distinct CNS regions, including cerebral cortex, hippocampus, thalamus, brainstem, and spinal cord. Red fluorescent mitochondria were visualized in cerebral cortical and hippocampal pyramidal neurons, ventrobasal thalamic neurons, subthalamic neurons, and spinal motor neurons. For the purpose of proof of principle application, these mice were used in excitotoxicity paradigms and double transgenic mice were generated by crossing Thy1-mitoDsRed2 mice with transgenic mice expressing enhanced-GFP (eGFP under the control of the Hlxb9 promoter that drives eGFP expression specifically in motor neurons and by crossing Thy1-mitoDsRed2 mice to amyotrophic lateral sclerosis (ALS mice expressing human mutant superoxide dismutase-1. Conclusions These novel transgenic mice will be a useful tool for better understanding

  16. Abnormal neuronal activity in Tourette syndrome and its modulation using deep brain stimulation.

    Science.gov (United States)

    Israelashvili, Michal; Loewenstern, Yocheved; Bar-Gad, Izhar

    2015-07-01

    Tourette syndrome (TS) is a common childhood-onset disorder characterized by motor and vocal tics that are typically accompanied by a multitude of comorbid symptoms. Pharmacological treatment options are limited, which has led to the exploration of deep brain stimulation (DBS) as a possible treatment for severe cases. Multiple lines of evidence have linked TS with abnormalities in the motor and limbic cortico-basal ganglia (CBG) pathways. Neurophysiological data have only recently started to slowly accumulate from multiple sources: noninvasive imaging and electrophysiological techniques, invasive electrophysiological recordings in TS patients undergoing DBS implantation surgery, and animal models of the disorder. These converging sources point to system-level physiological changes throughout the CBG pathway, including both general altered baseline neuronal activity patterns and specific tic-related activity. DBS has been applied to different regions along the motor and limbic pathways, primarily to the globus pallidus internus, thalamic nuclei, and nucleus accumbens. In line with the findings that also draw on the more abundant application of DBS to Parkinson's disease, this stimulation is assumed to result in changes in the neuronal firing patterns and the passage of information through the stimulated nuclei. We present an overview of recent experimental findings on abnormal neuronal activity associated with TS and the changes in this activity following DBS. These findings are then discussed in the context of current models of CBG function in the normal state, during TS, and finally in the wider context of DBS in CBG-related disorders. Copyright © 2015 the American Physiological Society.

  17. Distributed processing and temporal codes in neuronal networks.

    Science.gov (United States)

    Singer, Wolf

    2009-09-01

    The cerebral cortex presents itself as a distributed dynamical system with the characteristics of a small world network. The neuronal correlates of cognitive and executive processes often appear to consist of the coordinated activity of large assemblies of widely distributed neurons. These features require mechanisms for the selective routing of signals across densely interconnected networks, the flexible and context dependent binding of neuronal groups into functionally coherent assemblies and the task and attention dependent integration of subsystems. In order to implement these mechanisms, it is proposed that neuronal responses should convey two orthogonal messages in parallel. They should indicate (1) the presence of the feature to which they are tuned and (2) with which other neurons (specific target cells or members of a coherent assembly) they are communicating. The first message is encoded in the discharge frequency of the neurons (rate code) and it is proposed that the second message is contained in the precise timing relationships between individual spikes of distributed neurons (temporal code). It is further proposed that these precise timing relations are established either by the timing of external events (stimulus locking) or by internal timing mechanisms. The latter are assumed to consist of an oscillatory modulation of neuronal responses in different frequency bands that cover a broad frequency range from 40 Hz (gamma) and ripples. These oscillations limit the communication of cells to short temporal windows whereby the duration of these windows decreases with oscillation frequency. Thus, by varying the phase relationship between oscillating groups, networks of functionally cooperating neurons can be flexibly configurated within hard wired networks. Moreover, by synchronizing the spikes emitted by neuronal populations, the saliency of their responses can be enhanced due to the coincidence sensitivity of receiving neurons in very much the same way as

  18. [Brain and memory: new neurons to remember].

    Science.gov (United States)

    Gros, Alexandra; Veyrac, Alexandra; Laroche, Serge

    2015-01-01

    A defining characteristic of the brain is its remarkable capacity to undergo activity-dependent functional and structural remodelling via mechanisms of plasticity that form the basis of our capacity to encode and retain memories. The prevailing model of how our brain stores new information about relationships between events or new abstract constructs suggests it resides in activity-driven modifications of synaptic strength and remodelling of neural networks brought about by cellular and molecular changes within the neurons activated during learning. To date, the idea that a form of activity-dependent synaptic plasticity known as long-term potentiation, or LTP, and the associated synaptic growth play a central role in the laying down of memories has received considerable support. Beyond this mechanism of plasticity at the synapse, adult neurogenesis, i.e. the birth and growth of new neurons, is another form of neural plasticity that occurs continuously in defined brain regions such as the dentate gyrus of the hippocampus. Here, based on work in the hippocampus, we review the processes and mechanisms of the generation and selection of new neurons in the adult brain and the accumulating evidence that supports the idea that this form of neural plasticity is essential to store and lead to retrievable hippocampal-dependent memories. © Société de Biologie, 2016.

  19. Overproduction of Upper-Layer Neurons in the Neocortex Leads to Autism-like Features in Mice

    Directory of Open Access Journals (Sweden)

    Wei-Qun Fang

    2014-12-01

    Full Text Available The functional integrity of the neocortex depends upon proper numbers of excitatory and inhibitory neurons; however, the consequences of dysregulated neuronal production during the development of the neocortex are unclear. As excess cortical neurons are linked to the neurodevelopmental disorder autism, we investigated whether the overproduction of neurons leads to neocortical malformation and malfunction in mice. We experimentally increased the number of pyramidal neurons in the upper neocortical layers by using the small molecule XAV939 to expand the intermediate progenitor population. The resultant overpopulation of neurons perturbs development of dendrites and spines of excitatory neurons and alters the laminar distribution of interneurons. Furthermore, these phenotypic changes are accompanied by dysregulated excitatory and inhibitory synaptic connection and balance. Importantly, these mice exhibit behavioral abnormalities resembling those of human autism. Thus, our findings collectively suggest a causal relationship between neuronal overproduction and autism-like features, providing developmental insights into the etiology of autism.

  20. Motor neuron disease: the impact of decreased speech intelligibility ...

    African Journals Online (AJOL)

    Background: The onset of motor neuron disease (MND), a neurodegenerative disease, results in physical and communication disabilities that impinge on an individual's ability to remain functionally independent. Multiple aspects of the marital relationship are affected by the continuously changing roles and responsibilities.

  1. Neuronal avalanches and coherence potentials

    Science.gov (United States)

    Plenz, D.

    2012-05-01

    The mammalian cortex consists of a vast network of weakly interacting excitable cells called neurons. Neurons must synchronize their activities in order to trigger activity in neighboring neurons. Moreover, interactions must be carefully regulated to remain weak (but not too weak) such that cascades of active neuronal groups avoid explosive growth yet allow for activity propagation over long-distances. Such a balance is robustly realized for neuronal avalanches, which are defined as cortical activity cascades that follow precise power laws. In experiments, scale-invariant neuronal avalanche dynamics have been observed during spontaneous cortical activity in isolated preparations in vitro as well as in the ongoing cortical activity of awake animals and in humans. Theory, models, and experiments suggest that neuronal avalanches are the signature of brain function near criticality at which the cortex optimally responds to inputs and maximizes its information capacity. Importantly, avalanche dynamics allow for the emergence of a subset of avalanches, the coherence potentials. They emerge when the synchronization of a local neuronal group exceeds a local threshold, at which the system spawns replicas of the local group activity at distant network sites. The functional importance of coherence potentials will be discussed in the context of propagating structures, such as gliders in balanced cellular automata. Gliders constitute local population dynamics that replicate in space after a finite number of generations and are thought to provide cellular automata with universal computation. Avalanches and coherence potentials are proposed to constitute a modern framework of cortical synchronization dynamics that underlies brain function.

  2. [Neurons and values].

    Science.gov (United States)

    Camps, Victoria

    2013-09-01

    This article examines the advances made by neuroscience in the attempt to find an answer to the question regarding the origin and foundation of moral judgements and of human behaviour in compliance with them. The conception of the brain as something dynamic and capable of adapting to the social and cultural surroundings is seen to be an important point for philosophy. At the same time, the complexity of ethical issues that cannot be reduced to observations based strictly on neurons alone also becomes quite apparent. Nevertheless, scientists and philosophers should get together and communicate with one another so as to be able to pose their questions with greater rigour and take advantage of each other's respective knowledge.

  3. Morphological heterogeneity of layer VI neurons in mouse barrel cortex.

    Science.gov (United States)

    Chen, Chia-Chien; Abrams, Svetlana; Pinhas, Alex; Brumberg, Joshua C

    2009-02-20

    Understanding the basic neuronal building blocks of the neocortex is a necessary first step toward comprehending the composition of cortical circuits. Neocortical layer VI is the most morphologically diverse layer and plays a pivotal role in gating information to the cortex via its feedback connection to the thalamus and other ipsilateral and callosal corticocortical connections. The heterogeneity of function within this layer is presumably linked to its varied morphological composition. However, so far, very few studies have attempted to define cell classes in this layer using unbiased quantitative methodologies. Utilizing the Golgi staining technique along with the Neurolucida software, we recontructed 222 cortical neurons from layer VI of mouse barrel cortex. Morphological analyses were performed by quantifying somatic and dendritic parameters, and, by using principal component and cluster analyses, we quantitatively categorized neurons into six distinct morphological groups. Additional systematic replication on a separate population of neurons yielded similar results, demonstrating the consistency and reliability of our categorization methodology. Subsequent post hoc analyses of dendritic parameters supported our neuronal classification scheme. Characterizing neuronal elements with unbiased quantitative techniques provides a framework for better understanding structure-function relationships within neocortical circuits in general.

  4. Dorsomedial SCN neuronal subpopulations subserve different functions in human dementia

    Science.gov (United States)

    Harper, David G.; Stopa, Edward G.; Kuo-Leblanc, Victoria; McKee, Ann C.; Asayama, Kentaro; Volicer, Ladislav; Kowall, Neil; Satlin, Andrew

    2012-01-01

    The suprachiasmatic nuclei (SCN) are necessary and sufficient for the maintenance of circadian rhythms in primate and other mammalian species. The human dorsomedial SCN contains populations of non-species-specific vasopressin and species-specific neurotensin neurons. We made time-series recordings of core body temperature and locomotor activity in 19 elderly, male, end-stage dementia patients and 8 normal elderly controls. Following the death of the dementia patients, neuropathological diagnostic information and tissue samples from the hypothalamus were obtained. Hypothalamic tissue was also obtained from eight normal control cases that had not had activity or core temperature recordings previously. Core temperature was analysed for parametric, circadian features, and activity was analysed for non-parametric and parametric circadian features. These indices were then correlated with the degree of degeneration seen in the SCN (glia/neuron ratio) and neuronal counts from the dorsomedial SCN (vasopressin, neurotensin). Specific loss of SCN neurotensin neurons was associated with loss of activity and temperature amplitude without increase in activity fragmentation. Loss of SCN vasopressin neurons was associated with increased activity fragmentation but not loss of amplitude. Evidence for a circadian rhythm of vasopressinergic activity was seen in the dementia cases but no evidence was seen for a circadian rhythm in neurotensinergic activity. These results provide evidence that the SCN is necessary for the maintenance of the circadian rhythmin humans, information on the role of neuronal subpopulations in subserving this function and the utility of dementia in elaborating brain–behaviour relationships in the human. PMID:18372313

  5. Multiplying with Neurons

    Science.gov (United States)

    Gabbiani, F.; Krapp, H.; Koch, C.; Laurent, G.

    1998-03-01

    LGMD and DCMD are a pair of identified neurons in the locust brain thought to be involved in visually triggered escape behavior. LGMD integrates visual inputs in its dendritic arbor, converts them into spikes transmitted in a 1:1 manner to DCMD which relays this information to motor centers. We measured the spike activity of DCMD during simulated object approach and observed that its peak occured prior to the expected collision. The time difference between peak activity and collision depended linearly on the ratio of object size to approach velocity, as expected if LGMD/DCMD were detecting the moment in time when the approaching object reaches a fixed angular threshold θ_thresh on the locust's retina. The response of LGMD/DCMD could be fitted by multiplying the angular velocity at which an approaching object is increasing in size over the retina, dot θ, with an exponential function of the object's angular size, θ: f(t) = g(dot θ(t-δ) e^-α θ(t-δ)) where g is a static non-linearity, α a constant related to the angular threshold detected by LGMD/DCMD (θ_thresh = arctan (2/α)) and δ denotes the lag of the neuronal response with respect to the stimulus. This suggests that LGMD/DCMD derives its angular threshold sensitivity by multiplying dot θ with an exponential of θ. A biophysical implementation would be through linear summation of excitatory and inhibitory inputs proportional to log(dot θ) and -α θ, followed by a conversion to spike rate according to the static non-linearity (g circ exp). We have performed several experiments to test this hypothesis.

  6. Dynamic range and sensitivity adaptation in a silicon spiking neuron.

    Science.gov (United States)

    Shin, J; Koch, C

    1999-01-01

    We here propose an adaptive procedure that enables a spiking neuron, whether artificial or biological, to make optimal use of its dynamic range and gain.We discuss an analog electronic circuit implementation of this algorithm using a biologically realistic artificial "silicon" neuron. The adaptation procedure adapts the neuron's firing threshold and the sensitivity (or gain) of its current-frequency relationship to match the dc offset (or mean) and the dynamic range (or variance) of the time-varying somatic input current. The neuron extracts the minimum and maximum levels of the reconstructed somatic current signals from the cell's own spike trains. These are used to regulate the somatic leak conductance in order to shift the somatic current-frequency relation and to adjust a calcium-activated potassium conductance to change the dynamic range of the cell's somatic current-frequency relationship. We report experimental data from a test neuron--built using analog subthreshold CMOS VLSI technology--that shows the expected behavior.

  7. Rat prefrontal cortical neurons selectively code strategy switches.

    Science.gov (United States)

    Rich, Erin L; Shapiro, Matthew

    2009-06-03

    Multiple memory systems are distinguished by different sets of neuronal circuits and operating principles optimized to solve different problems across mammalian species (Tulving and Schacter, 1994). When a rat selects an arm in a plus maze, for example, the choice can be guided by distinct neural systems (White and Wise, 1999) that encode different relationships among perceived stimuli, actions, and reward. Thus, egocentric or stimulus-response associations require striatal circuits, whereas spatial or episodic learning requires hippocampal circuits (Packard et al., 1989). Although these memory systems function in parallel (Packard and McGaugh, 1996), they can also interact competitively or synergistically (Kim and Ragozzino, 2005). The neuronal mechanisms that coordinate these multiple memory systems are not fully known, but converging evidence suggests that the prefrontal cortex (PFC) is central. The PFC is crucial for abstract, rule-guided behavior in primates and for switching rapidly between memory strategies in rats. We now report that rat medial PFC neuronal activity predicts switching between hippocampus- and caudate-dependent memory strategies. Prelimbic (PL) and infralimbic (IL) neuronal activity changed as rats switched memory strategies even as the rats performed identical behaviors but did not change when rats learned new contingencies using the same strategy. PL dynamics anticipated learning performance whereas IL lagged, suggesting that the two regions help initiate and establish new strategies, respectively. These neuronal dynamics suggest that the PFC contributes to the coordination of memory strategies by integrating the predictive relationships among stimuli, actions, and reward.

  8. Postmitotic specification of Drosophila insulinergic neurons from pioneer neurons.

    Directory of Open Access Journals (Sweden)

    Irene Miguel-Aliaga

    2008-03-01

    Full Text Available Insulin and related peptides play important and conserved functions in growth and metabolism. Although Drosophila has proved useful for the genetic analysis of insulin functions, little is known about the transcription factors and cell lineages involved in insulin production. Within the embryonic central nervous system, the MP2 neuroblast divides once to generate a dMP2 neuron that initially functions as a pioneer, guiding the axons of other later-born embryonic neurons. Later during development, dMP2 neurons in anterior segments undergo apoptosis but their posterior counterparts persist. We show here that surviving posterior dMP2 neurons no longer function in axonal scaffolding but differentiate into neuroendocrine cells that express insulin-like peptide 7 (Ilp7 and innervate the hindgut. We find that the postmitotic transition from pioneer to insulin-producing neuron is a multistep process requiring retrograde bone morphogenetic protein (BMP signalling and four transcription factors: Abdominal-B, Hb9, Fork Head, and Dimmed. These five inputs contribute in a partially overlapping manner to combinatorial codes for dMP2 apoptosis, survival, and insulinergic differentiation. Ectopic reconstitution of this code is sufficient to activate Ilp7 expression in other postmitotic neurons. These studies reveal striking similarities between the transcription factors regulating insulin expression in insect neurons and mammalian pancreatic beta-cells.

  9. Cochlear nucleus neuron analysis in individuals with presbycusis.

    Science.gov (United States)

    Hinojosa, Raul; Nelson, Erik G

    2011-12-01

    The aim of this study was to analyze the cochlear nucleus neuron population in individuals with normal hearing and presbycusis. Retrospective study of archival human temporal bone and brain stem tissues. Using strict inclusion criteria, the temporal bones and cochlear nuclei from six normal hearing individuals and four individuals with presbycusis were selected for analysis. The spiral ganglion cell population, the cochlear nucleus neuron population, and the cell body size of the neurons were quantified in these cases. A relationship was not observed between age and the spiral ganglion cell population in the normal hearing group. Presbycusis subjects exhibited a reduced spiral ganglion cell population. The mean cochlear nucleus neuron population was observed to be significantly higher in the presbycusis group (mean ± standard deviation: 114,170 ± 10,570) compared to the normal hearing group (91,470 ± 9,510) (P = .019). This difference was predominantly the result of greater multipolar and granule cell neuron populations. Only the fusiform neuron type exhibited a significantly different mean cell body cross-sectional area between the normal hearing group (242 ± 27) and the presbycusis group (300 ± 37) (P = .033). This investigation is the first time, to our knowledge, that the populations of the eight neuron types in the cochlear nucleus have been quantified in both normal hearing individuals and individuals with presbycusis. The data support the concept that presbycusis is not an effect of aging alone but instead may be a condition that predisposes one to hearing loss with advancing age and is characterized by a congenitally elevated cochlear nucleus neuron population. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

  10. Differential expression of alpha-synuclein in hippocampal neurons.

    Directory of Open Access Journals (Sweden)

    Katsutoshi Taguchi

    Full Text Available α-Synuclein is the major pathological component of synucleinopathies including Parkinson's disease and dementia with Lewy bodies. Recent studies have demonstrated that α-synuclein also plays important roles in the release of synaptic vesicles and synaptic membrane recycling in healthy neurons. However, the precise relationship between the pathogenicity and physiological functions of α-synuclein remains to be elucidated. To address this issue, we investigated the subcellular localization of α-synuclein in normal and pathological conditions using primary mouse hippocampal neuronal cultures. While some neurons expressed high levels of α-synuclein in presynaptic boutons and cell bodies, other neurons either did not or only very weakly expressed the protein. These α-synuclein-negative cells were identified as inhibitory neurons by immunostaining with specific antibodies against glutamic acid decarboxylase (GAD, parvalbumin, and somatostatin. In contrast, α-synuclein-positive synapses were colocalized with the excitatory synapse marker vesicular glutamate transporter-1. This expression profile of α-synuclein was conserved in the hippocampus in vivo. In addition, we found that while presynaptic α-synuclein colocalizes with synapsin, a marker of presynaptic vesicles, it is not essential for activity-dependent membrane recycling induced by high potassium treatment. Exogenous supply of preformed fibrils generated by recombinant α-synuclein was shown to promote the formation of Lewy body (LB -like intracellular aggregates involving endogenous α-synuclein. GAD-positive neurons did not form LB-like aggregates following treatment with preformed fibrils, however, exogenous expression of human α-synuclein allowed intracellular aggregate formation in these cells. These results suggest the presence of a different mechanism for regulation of the expression of α-synuclein between excitatory and inhibitory neurons. Furthermore, α-synuclein expression

  11. 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.

  12. Preferred transduction with AAV8 and AAV9 via thalamic administration in the MPS IIIB model: A comparison of four rAAV serotypes

    Directory of Open Access Journals (Sweden)

    J.A. Gilkes

    2016-03-01

    Full Text Available Sanfilippo syndrome type B (MPS IIIB is a lysosomal storage disease caused by a deficiency of N-acetyl-glucosaminidase (NAGLU activity. Since early therapeutic intervention is likely to yield the most efficacious results, we sought to determine the possible therapeutic utility of rAAV in early gene therapy based interventions. Currently, the application of recombinant adeno-associated virus (AAV vectors is one of the most widely used gene transfer systems, and represents a promising approach in the treatment of MPS IIIB. From a translational standpoint, a minimally invasive, yet highly efficient method of vector administration is ideal. The thalamus is thought to be the switchboard for signal relay in the central nervous system (CNS and therefore represents an attractive target. To identify an optimal AAV vector for early therapeutic intervention, and establish whether thalamic administration represents a feasible therapeutic approach, we performed a comprehensive assessment of transduction and biodistribution profiles of four green fluorescent protein (GFP bearing rAAV serotypes, -5, -8, -9 and -rh10, administered bilaterally into the thalamus. Of the four serotypes compared, AAV8 and -9 proved superior to AAV5 and -rh10 both in biodistribution and transduction efficiency profiles. Genotype differences in transduction efficiency and biodistribution patterns were also observed. Importantly, we conclude that AAV8 and to a lesser extent, AAV9 represent preferable candidates for early gene therapy based intervention in the treatment of MPS IIIB. We also highlight the feasibility of thalamic rAAV administration, and conclude that this method results in moderate rAAV biodistribution with limited treatment capacity, thus suggesting a need for alternate methods of vector delivery.

  13. Delimitação dos núcleos talâmicos pela eletrofisiologia estereotáxica Delimitation of the thalamic nuclei by stereotaxic electrophysiology

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    Nilton Luís Latuf

    1973-12-01

    Full Text Available Os limites da área destruída durante a cirurgia estereotáxica são descritos levando em consideração as complicações decorrentes de lesões determinadas erroneamente. São comentados os métodos empregados com a finalidade de controlar a delimitação do alvo, sendo descrita a técnica usada em 23 talamotomias com derivação da atividade elétrica celular dos núcleos talâmicos atravessados e a pesquisa de potenciais evocados, graças à somatotopia da representação táctil no núcleo ventral posterior. Com este método reduz-se de mais ou menos 1 mm o erro radiológico, prescisando-se o alvo terapêutico talâmico nos três planos de espaço.The limits of the area to be destroyed during the stereotaxic surgery for the treatment of tremors are described taking into account the complications due to lesions erroneously performed. The method applied is commented in order to control the accuracy of the target delimitation, describing the technique employed in 23 thalamotomies, recording the electrical activity of the thalamic nuclei acrossed and researching evoked potentials thanks to the somatotopic tactil representation in the ventral posterior nuclei. The method permits to reduce radiologic errors giving more accuracy for the delimitation of thalamic target in the three planes of space.

  14. [Development of intellect, emotion, and intentions, and their neuronal systems].

    Science.gov (United States)

    Segawa, Masaya

    2008-09-01

    Intellect, emotion and intentions, the major components of the human mentality, are neurologically correlated to memory and sensorimotor integration, the neuronal system consisting of the amygdale and hypothalamus, and motivation and learning, respectively. Development of these neuronal processes was evaluated by correlating the pathophysiologies of idiopathic developmental neuropsychiatric disorders and developmental courses of sleep parameters, sleep-wake rhythm (SWR), and locomotion. The memory system and sensory pathways develop by the 9th gestational months. Habituation or dorsal bundle extinction (DBE) develop after the 34th gestational week. In the first 4 months after birth, DBE is consolidated and fine tuning of the primary sensory cortex and its neuronal connection to the unimodal sensory association area along with functional lateralization of the cortex are accomplished. After 4 months, restriction of atonia in the REM stage enables the integrative function of the brain and induces synaptogenesis of the cortex around 6 months and locomotion in late infancy by activating the dopaminergic (DA) neurons induces synaptogenesis of the frontal cortex. Locomotion in early infancy involves functional specialization of the cortex and in childhood with development of biphasic SWR activation of the areas of the prefrontal cortex. Development of emotions reflects in the development of personal communication and the arousal function of the hypothalamus. The former is shown in the mother-child relationship in the first 4 months, in communication with adults and playmates in late infancy to early childhood, and in development of social relationships with sympathy by the early school age with functional maturation of the orbitofrontal cortex. The latter is demonstrated in the secretion of melatonin during night time by 4 months, in the circadian rhythm of body temperature by 8 months, and in the secretion of the growth hormone by 4-5 years with synchronization to the

  15. Granger Causality Network Reconstruction of Conductance-Based Integrate-and-Fire Neuronal Systems

    Science.gov (United States)

    Zhou, Douglas; Xiao, Yanyang; Zhang, Yaoyu; Xu, Zhiqin; Cai, David

    2014-01-01

    Reconstruction of anatomical connectivity from measured dynamical activities of coupled neurons is one of the fundamental issues in the understanding of structure-function relationship of neuronal circuitry. Many approaches have been developed to address this issue based on either electrical or metabolic data observed in experiment. The Granger causality (GC) analysis remains one of the major approaches to explore the dynamical causal connectivity among individual neurons or neuronal populations. However, it is yet to be clarified how such causal connectivity, i.e., the GC connectivity, can be mapped to the underlying anatomical connectivity in neuronal networks. We perform the GC analysis on the conductance-based integrate-and-fire (IF) neuronal networks to obtain their causal connectivity. Through numerical experiments, we find that the underlying synaptic connectivity amongst individual neurons or subnetworks, can be successfully reconstructed by the GC connectivity constructed from voltage time series. Furthermore, this reconstruction is insensitive to dynamical regimes and can be achieved without perturbing systems and prior knowledge of neuronal model parameters. Surprisingly, the synaptic connectivity can even be reconstructed by merely knowing the raster of systems, i.e., spike timing of neurons. Using spike-triggered correlation techniques, we establish a direct mapping between the causal connectivity and the synaptic connectivity for the conductance-based IF neuronal networks, and show the GC is quadratically related to the coupling strength. The theoretical approach we develop here may provide a framework for examining the validity of the GC analysis in other settings. PMID:24586285

  16. Correlations between neuronal morphology and electrophysiological features in the rodent superficial dorsal horn

    Science.gov (United States)

    Grudt, T J; Perl, E R

    2002-01-01

    Relationships between the morphology of individual neurones of the spinal superficial dorsal horn (SDH), laminae I and II, and their electrophysiological properties were studied in spinal cord slices prepared from anaesthetized, free-ranging hamsters. Tight-seal, whole-cell recordings were made with pipette microelectrodes filled with biocytin to establish electrophysiological characteristics and to label the studied neurones. Neurones were categorized according to location and size of the somata, the dendritic and axonal pattern of arborization, spontaneous synaptic potentials, evoked postsynaptic currents, pattern of discharge to depolarizing pulses and current-voltage relationships. Data were obtained for 170 neurones; 13 of these had somata in lamina I and 157 in lamina II. Stimulation of the segmental dorsal root evoked a prompt excitatory response in almost every neurone sampled (161/166) with nearly 3/4 displaying putative monosynaptic EPSCs. The majority of neurones (133/170) fitted one of several distinctive morphological categories. To a considerable extent, neurones with a common morphological configuration and neurite disposition shared electrophysiological characteristics. Five of the 13 lamina I neurones were relatively large with extensive dendritic arborization in the horizontal dimension and a prominent axon directed ventrally and contralaterally. These presumptive ventrolateral projection neurones differed structurally and electrophysiologically from the other lamina I neurones, which had ipsilateral, locally arborizing axons and/or branches entering the dorsal lateral funiculus. One hundred and twenty lamina II neurones fitted one of five morphological categories: islet, central, medial-lateral, radial or vertical. Central cells were further divided into three groups on functional features. We conclude that the spinal SDH comprises many types of neurones whose morphological characteristics are associated with specific functional features implying

  17. A Neuron Model for FPGA Spiking Neuronal Network Implementation

    Directory of Open Access Journals (Sweden)

    BONTEANU, G.

    2011-11-01

    Full Text Available We propose a neuron model, able to reproduce the basic elements of the neuronal dynamics, optimized for digital implementation of Spiking Neural Networks. Its architecture is structured in two major blocks, a datapath and a control unit. The datapath consists of a membrane potential circuit, which emulates the neuronal dynamics at the soma level, and a synaptic circuit used to update the synaptic weight according to the spike timing dependent plasticity (STDP mechanism. The proposed model is implemented into a Cyclone II-Altera FPGA device. Our results indicate the neuron model can be used to build up 1K Spiking Neural Networks on reconfigurable logic suport, to explore various network topologies.

  18. Neuronal responses to physiological stress

    DEFF Research Database (Denmark)

    Kagias, Konstantinos; Nehammer, Camilla; Pocock, Roger David John

    2012-01-01

    damage during aging that results in decline and eventual death. Studies have shown that the nervous system plays a pivotal role in responding to stress. Neurons not only receive and process information from the environment but also actively respond to various stresses to promote survival. These responses...... include changes in the expression of molecules such as transcription factors and microRNAs that regulate stress resistance and adaptation. Moreover, both intrinsic and extrinsic stresses have a tremendous impact on neuronal development and maintenance with implications in many diseases. Here, we review...... the responses of neurons to various physiological stressors at the molecular and cellular level....

  19. Evidence of involvement of neurone-glia/neurone-neurone communications via gap junctions in synchronised activity of KNDy neurones.

    Science.gov (United States)

    Ikegami, K; Minabe, S; Ieda, N; Goto, T; Sugimoto, A; Nakamura, S; Inoue, N; Oishi, S; Maturana, A D; Sanbo, M; Hirabayashi, M; Maeda, K-I; Tsukamura, H; Uenoyama, Y

    2017-06-01

    Pulsatile secretion of gonadotrophin-releasing hormone (GnRH)/luteinising hormone is indispensable for the onset of puberty and reproductive activities at adulthood in mammalian species. A cohort of neurones expressing three neuropeptides, namely kisspeptin, encoded by the Kiss1 gene, neurokinin B (NKB) and dynorphin A, localised in the hypothalamic arcuate nucleus (ARC), so-called KNDy neurones, comprises a putative intrinsic source of the GnRH pulse generator. Synchronous activity among KNDy neurones is considered to be required for pulsatile GnRH secretion. It has been reported that gap junctions play a key role in synchronising electrical activity in the central nervous system. Thus, we hypothesised that gap junctions are involved in the synchronised activities of KNDy neurones, which is induced by NKB-NK3R signalling. We determined the role of NKB-NK3R signalling in Ca 2+ oscillation (an indicator of neuronal activities) of KNDy neurones and its synchronisation mechanism among KNDy neurones. Senktide, a selective agonist for NK3R, increased the frequency of Ca 2+ oscillations in cultured Kiss1-GFP cells collected from the mediobasal hypothalamus of the foetal Kiss1-green fluorescent protein (GFP) mice. The senktide-induced Ca 2+ oscillations were synchronised in the Kiss1-GFP and neighbouring glial cells. Confocal microscopy analysis of these cells, which have shown synchronised Ca 2+ oscillations, revealed close contacts between Kiss1-GFP cells, as well as between Kiss1-GFP cells and glial cells. Dye coupling experiments suggest cell-to-cell communication through gap junctions between Kiss1-GFP cells and neighbouring glial cells. Connexin-26 and -37 mRNA were found in isolated ARC Kiss1 cells taken from adult female Kiss1-GFP transgenic mice. Furthermore, 18β-glycyrrhetinic acids and mefloquine, which are gap junction inhibitors, attenuated senktide-induced Ca 2+ oscillations in Kiss1-GFP cells. Taken together, these results suggest that NKB-NK3R signalling

  20. Nonsulfated cholecystokinins in cerebral neurons

    DEFF Research Database (Denmark)

    Agersnap, Mikkel; Zhang, Ming-Dong; Harkany, Tibor

    2016-01-01

    Cholecystokinin (CCK) is a widely expressed neuropeptide system originally discovered in the gut. Both cerebral and peripheral neurons as well as endocrine I-cells in the small intestine process proCCK to tyrosyl-O-sulfated and α-carboxyamidated peptides. Recently, we reported that gut endocrine I...... for nonsulfated CCK-8 with an antibody recognizing both sulfated and nonsulfated CCK. However, nonsulfated CCK immunoreactivity was stronger than that of sulfated CCK in cell bodies and weaker in nerve terminals. We conclude that only a small fraction of neuronal CCK is nonsulfated. The intracellular distribution...... of nonsulfated CCK in neurons suggests that they contribute only modestly to the CCK transmitter activity....

  1. Neurones and neuropeptides in coelenterates

    DEFF Research Database (Denmark)

    Grimmelikhuijzen, C J; Ebbesen, Ditte Graff; McFarlane, I D

    1989-01-01

    The first nervous system probably evolved in coelenterates. Many neurons in coelenterates have morphological characteristics of both sensory and motor neurones, and appear to be multifunctional. Using immunocytochemistry with antisera to the sequence Arg-Phe-NH2 (RFamide), RFamide-like peptides......) was isolated, which also belongs to the less than Glu...Arg-X-NH2 family. Using specific antisera it was shown that all four peptides were located in neurones. Application of low doses of Antho-RFamide, or Antho-RWamide I or II induced contractions of endodermal muscles of sea anemones. This indicates...

  2. Statistical inference on spontaneous neuronal discharge patterns. I. Single neuron.

    Science.gov (United States)

    Lánský, P; Radil, T

    1987-01-01

    A statistical analysis was performed on extracellularly recorded spike trains of spontaneously active mesencephalic reticular neurons of rats. Only stationary records were used for detailed examination. The moments of interspike intervals were computed, hypothesis of renewal process and its specific forms was tested. Implications for statistical methodology are considered on the basis of the results. The main emphasis is laid on the connection between experimental results and stochastic neuronal models.

  3. Distribution of neurons in functional areas of the mouse cerebral cortex reveals quantitatively different cortical zones

    Science.gov (United States)

    Herculano-Houzel, Suzana; Watson, Charles; Paxinos, George

    2013-01-01

    How are neurons distributed along the cortical surface and across functional areas? Here we use the isotropic fractionator (Herculano-Houzel and Lent, 2005) to analyze the distribution of neurons across the entire isocortex of the mouse, divided into 18 functional areas defined anatomically. We find that the number of neurons underneath a surface area (the N/A ratio) varies 4.5-fold across functional areas and neuronal density varies 3.2-fold. The face area of S1 contains the most neurons, followed by motor cortex and the primary visual cortex. Remarkably, while the distribution of neurons across functional areas does not accompany the distribution of surface area, it mirrors closely the distribution of cortical volumes—with the exception of the visual areas, which hold more neurons than expected for their volume. Across the non-visual cortex, the volume of individual functional areas is a shared linear function of their number of neurons, while in the visual areas, neuronal densities are much higher than in all other areas. In contrast, the 18 functional areas cluster into three different zones according to the relationship between the N/A ratio and cortical thickness and neuronal density: these three clusters can be called visual, sensory, and, possibly, associative. These findings are remarkably similar to those in the human cerebral cortex (Ribeiro et al., 2013) and suggest that, like the human cerebral cortex, the mouse cerebral cortex comprises two zones that differ in how neurons form the cortical volume, and three zones that differ in how neurons are distributed underneath the cortical surface, possibly in relation to local differences in connectivity through the white matter. Our results suggest that beyond the developmental divide into visual and non-visual cortex, functional areas initially share a common distribution of neurons along the parenchyma that become delimited into functional areas according to the pattern of connectivity established later

  4. Distribution of neurons in functional areas of the mouse cerebral cortex reveals quantitatively different cortical zones

    Directory of Open Access Journals (Sweden)

    Suzana eHerculano-Houzel

    2013-10-01

    Full Text Available How are neurons distributed along the cortical surface and across functional areas? Here we use the isotropic fractionator (Herculano-Houzel and Lent, 2005 to analyze the distribution of neurons across the entire isocortex of the mouse, divided into 18 functional areas defined anatomically. We find that the number of neurons underneath a surface area (the N/A ratio varies 4.5-fold across functional areas and neuronal density varies 3.2-fold. The face area of S1 contains the most neurons, followed by motor cortex and the primary visual cortex. Remarkably, while the distribution of neurons across functional areas does not accompany the distribution of surface area, it mirrors closely the distribution of cortical volumes – with the exception of the visual areas, which hold more neurons than expected for their volume. Across the non-visual cortex, the volume of individual functional areas is a shared linear function of their number of neurons, while in the visual areas, neuronal densities are much higher than in all other areas. In contrast, the 18 functional areas cluster into three different zones according to the relationship between the N/A ratio and cortical thickness and neuronal density: these three clusters can be called visual, sensory, and, possibly, associative. These findings are remarkably similar to those in the human cerebral cortex (see companion paper and suggest that, like the human cerebral cortex, the mouse cerebral cortex comprises two zones that differ in how neurons form the cortical volume, and three zones that differ in how neurons are distributed underneath the cortical surface, possibly in relation to local differences in connectivity through the white matter. Our results suggest that beyond the developmental divide into visual and non-visual cortex, functional areas initially share a common distribution of neurons along the parenchyma that become delimited into functional areas according to the pattern of connectivity

  5. Neuronal boost to evolutionary dynamics.

    Science.gov (United States)

    de Vladar, Harold P; Szathmáry, Eörs

    2015-12-06

    Standard evolutionary dynamics is limited by the constraints of the genetic system. A central message of evolutionary neurodynamics is that evolutionary dynamics in the brain can happen in a neuronal niche in real time, despite the fact that neurons do not reproduce. We show that Hebbian learning and structural synaptic plasticity broaden the capacity for informational replication and guided variability provided a neuronally plausible mechanism of replication is in place. The synergy between learning and selection is more efficient than the equivalent search by mutation selection. We also consider asymmetric landscapes and show that the learning weights become correlated with the fitness gradient. That is, the neuronal complexes learn the local properties of the fitness landscape, resulting in the generation of variability directed towards the direction of fitness increase, as if mutations in a genetic pool were drawn such that they would increase reproductive success. Evolution might thus be more efficient within evolved brains than among organisms out in the wild.

  6. Information processing by neuronal populations

    National Research Council Canada - National Science Library

    Hölscher, Christian; Munk, Matthias

    2009-01-01

    ... simultaneously recorded spike trains 120 Mark Laubach, Nandakumar S. Narayanan, and Eyal Y. Kimchi Part III Neuronal population information coding and plasticity in specific brain areas 149 7 F...

  7. Hydrodynamic Limit for Interacting Neurons

    Science.gov (United States)

    De Masi, A.; Galves, A.; Löcherbach, E.; Presutti, E.

    2015-02-01

    This paper studies the hydrodynamic limit of a stochastic process describing the time evolution of a system with N neurons with mean-field interactions produced both by chemical and by electrical synapses. This system can be informally described as follows. Each neuron spikes randomly following a point process with rate depending on its membrane potential. At its spiking time, the membrane potential of the spiking neuron is reset to the value 0 and, simultaneously, the membrane potentials of the other neurons are increased by an amount of potential . This mimics the effect of chemical synapses. Additionally, the effect of electrical synapses is represented by a deterministic drift of all the membrane potentials towards the average value of the system. We show that, as the system size N diverges, the distribution of membrane potentials becomes deterministic and is described by a limit density which obeys a non linear PDE which is a conservation law of hyperbolic type.

  8. Brain scaling in mammalian evolution as a consequence of concerted and mosaic changes in numbers of neurons and average neuronal cell size

    Science.gov (United States)

    Herculano-Houzel, Suzana; Manger, Paul R.; Kaas, Jon H.

    2014-01-01

    Enough species have now been subject to systematic quantitative analysis of the relationship between the morphology and cellular composition of their brain that patterns begin to emerge and shed light on the evolutionary path that led to mammalian brain diversity. Based on an analysis of the shared and clade-specific characteristics of 41 modern mammalian species in 6 clades, and in light of the phylogenetic relationships among them, here we propose that ancestral mammal brains were composed and scaled in their cellular composition like modern afrotherian and glire brains: with an addition of neurons that is accompanied by a decrease in neuronal density and very little modification in glial cell density, implying a significant increase in average neuronal cell size in larger brains, and the allocation of approximately 2 neurons in the cerebral cortex and 8 neurons in the cerebellum for every neuron allocated to the rest of brain. We also propose that in some clades the scaling of different brain structures has diverged away from the common ancestral layout through clade-specific (or clade-defining) changes in how average neuronal cell mass relates to numbers of neurons in each structure, and how numbers of neurons are differentially allocated to each structure relative to the number of neurons in the rest of brain. Thus, the evolutionary expansion of mammalian brains has involved both concerted and mosaic patterns of scaling across structures. This is, to our knowledge, the first mechanistic model that explains the generation of brains large and small in mammalian evolution, and it opens up new horizons for seeking the cellular pathways and genes involved in brain evolution. PMID:25157220

  9. Brain scaling in mammalian evolution as a consequence of concerted and mosaic changes in numbers of neurons and average neuronal cell size

    Directory of Open Access Journals (Sweden)

    Suzana eHerculano-Houzel

    2014-08-01

    Full Text Available Enough species have now been subject to systematic quantitative analysis of the relationship between the morphology and cellular composition of their brain that patterns begin to emerge and shed light on the evolutionary path that led to mammalian brain diversity. Based on an analysis of the shared and clade-specific characteristics of 41 modern mammalian species in 6 clades, and in light of the phylogenetic relationships among them, here we propose that ancestral mammal brains were composed and scaled in their cellular composition like modern afrotherian and glire brains: with an addition of neurons that is accompanied by a decrease in neuronal density and very little modification in glial cell density, implying a significant increase in average neuronal cell size in larger brains, and the allocation of approximately 2 neurons in the cerebral cortex and 8 neurons in the cerebellum for every neuron allocated to the rest of brain. We also propose that in some clades the scaling of different brain structures has diverged away from the common ancestral layout through clade-specific (or clade-defining changes in how average neuronal cell mass relates to numbers of neurons in each structure, and how numbers of neurons are differentially allocated to each structure relative to the number of neurons in the rest of brain. Thus, the evolutionary expansion of mammalian brains has involved both concerted and mosaic patterns of scaling across structures. This is, to our knowledge, the first mechanistic model that explains the generation of brains large and small in mammalian evolution, and it opens up new horizons for seeking the cellular pathways and genes involved in brain evolution.

  10. Neuronal control of energy homeostasis

    OpenAIRE

    Gao, Qian; Horvath, Tamas L.

    2007-01-01

    Neuronal control of body energy homeostasis is the key mechanism by which animals and humans regulate their long-term energy balance. Various hypothalamic neuronal circuits (which include the hypothalamic melanocortin, midbrain dopamine reward and caudal brainstem autonomic feeding systems) control energy intake and expenditure to maintain body weight within a narrow range for long periods of a life span. Numerous peripheral metabolic hormones and nutrients target these structures providing f...

  11. Mirror neurons and their function in cognitively understood empathy.

    Science.gov (United States)

    Corradini, Antonella; Antonietti, Alessandro

    2013-09-01

    The current renewal of interest in empathy is closely connected to the recent neurobiological discovery of mirror neurons. Although the concept of empathy has been widely deployed, we shall focus upon one main psychological function it serves: enabling us to understand other peoples' intentions. In this essay we will draw on neuroscientific, psychological, and philosophical literature in order to investigate the relationships between mirror neurons and empathy as to intention understanding. Firstly, it will be explored whether mirror neurons are the neural basis of our empathic capacities: a vast array of empirical results appears to confirm this hypothesis. Secondly, the higher level capacity of reenactive empathy will be examined and the question will be addressed whether philosophical analysis alone is able to provide a foundation for this more abstract level of empathy. The conclusion will be drawn that both empirical evidence and philosophical analysis can jointly contribute to the clarification of the concept of empathy. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. A nonparametric stochastic optimizer for TDMA-based neuronal signaling.

    Science.gov (United States)

    Suzuki, Junichi; Phan, Dũng H; Budiman, Harry

    2014-09-01

    This paper considers neurons as a physical communication medium for intrabody networks of nano/micro-scale machines and formulates a noisy multiobjective optimization problem for a Time Division Multiple Access (TDMA) communication protocol atop the physical layer. The problem is to find the Pareto-optimal TDMA configurations that maximize communication performance (e.g., latency) by multiplexing a given neuronal network to parallelize signal transmissions while maximizing communication robustness (i.e., unlikeliness of signal interference) against noise in neuronal signaling. Using a nonparametric significance test, the proposed stochastic optimizer is designed to statistically determine the superior-inferior relationship between given two solution candidates and seek the optimal trade-offs among communication performance and robustness objectives. Simulation results show that the proposed optimizer efficiently obtains quality TDMA configurations in noisy environments and outperforms existing noise-aware stochastic optimizers.

  13. Psychiatric behaviors associated with cytoskeletal defects in radial neuronal migration.

    Science.gov (United States)

    Fukuda, Toshifumi; Yanagi, Shigeru

    2017-10-01

    Normal development of the cerebral cortex is an important process for higher brain functions, such as language, and cognitive and social functions. Psychiatric disorders, such as schizophrenia and autism, are thought to develop owing to various dysfunctions occurring during the development of the cerebral cortex. Radial neuronal migration in the embryonic cerebral cortex is a complex process, which is achieved by strict control of cytoskeletal dynamics, and impairments in this process are suggested to cause various psychiatric disorders. Our recent findings indicate that radial neuronal migration as well as psychiatric behaviors is rescued by controlling microtubule stability during the embryonic stage. In this review, we outline the relationship between psychiatric disorders, such as schizophrenia and autism, and radial neuronal migration in the cerebral cortex by focusing on the cytoskeleton and centrosomes. New treatment strategies for psychiatric disorders will be discussed.

  14. The Neuronal Transition Probability (NTP) Model for the Dynamic Progression of Non-REM Sleep EEG: The Role of the Suprachiasmatic Nucleus

    CERN Document Server

    Merica, H

    2011-01-01

    Little attention has gone into linking to its neuronal substrates the dynamic structure of non-rapid-eye-movement (NREM) sleep, defined as the pattern of time-course power in all frequency bands across an entire episode. Using the spectral power time-courses in the sleep electroencephalogram (EEG), we showed in the typical first episode, several moves towards-and-away from deep sleep, each having an identical pattern linking the major frequency bands beta, sigma and delta. The neuronal transition probability model (NTP) - in fitting the data well - successfully explained the pattern as resulting from stochastic transitions of the firing-rates of the thalamically-projecting brainstem-activating neurons, alternating between two steady dynamic-states (towards-and-away from deep sleep) each initiated by a so-far unidentified flip-flop. The aims here are to identify this flip-flop and to demonstrate that the model fits well all NREM episodes, not just the first. Using published data on suprachiasmatic nucleus (SCN...

  15. Novel model of neuronal bioenergetics

    DEFF Research Database (Denmark)

    Bak, Lasse Kristoffer; Obel, Linea Lykke Frimodt; Walls, Anne B

    2012-01-01

    We have previously investigated the relative roles of extracellular glucose and lactate as fuels for glutamatergic neurons during synaptic activity. The conclusion from these studies was that cultured glutamatergic neurons utilize glucose rather than lactate during NMDA (N-methyl-d-aspartate)-ind......We have previously investigated the relative roles of extracellular glucose and lactate as fuels for glutamatergic neurons during synaptic activity. The conclusion from these studies was that cultured glutamatergic neurons utilize glucose rather than lactate during NMDA (N...... of an ionomycin-induced increase in intracellular Ca2+ (i.e. independent of synaptic activity) on neuronal energy metabolism employing 13C-labelled glucose and lactate and subsequent mass spectrometric analysis of labelling in glutamate, alanine and lactate. The results demonstrate that glucose utilization...... is positively correlated with intracellular Ca2+ whereas lactate utilization is not. This result lends further support for a significant role of glucose in neuronal bioenergetics and that Ca2+ signalling may control the switch between glucose and lactate utilization during synaptic activity. Based...

  16. Unique aspects of transcriptional regulation in neurons – nuances in NFκB and Sp1-related factors

    Directory of Open Access Journals (Sweden)

    Chen Yuzhi

    2009-05-01

    Full Text Available Abstract The unique physiology and function of neurons create differences in their cellular physiology, including their regulation of gene expression. We began several years ago exploring the relationships between the NFκB transcription factor, neuronal survival, and glutamate receptor activation in telencephalic neurons. These studies led us to conclude that this population of cells is nearly incapable of activating the NFκB that is nonetheless expressed at reasonable levels. A subset of the κB cis elements are instead bound by members of the Sp1 family in neurons. Also surprising was our discovery that Sp1 itself, typically described as ubiquitous, is severely restricted in expression within forebrain neurons; Sp4 seems to be substituted during neuronal differentiation. These findings and their implications for neuronal differentiation – as well as potential dedifferentiation during degenerative processes – are discussed here.

  17. Verbal Memory Decline following DBS for Parkinson’s Disease: Structural Volumetric MRI Relationships

    Science.gov (United States)

    Geevarghese, Ruben; Lumsden, Daniel E.; Costello, Angela; Hulse, Natasha; Ayis, Salma; Samuel, Michael; Ashkan, Keyoumars

    2016-01-01

    Background Parkinson’s disease is a chronic degenerative movement disorder. The mainstay of treatment is medical. In certain patients Deep Brain Stimulation (DBS) may be offered. However, DBS has been associated with post-operative neuropsychology changes, especially in verbal memory. Objectives Firstly, to determine if pre-surgical thalamic and hippocampal volumes were related to verbal memory changes following DBS. Secondly, to determine if clinical factors such as age, duration of symptoms or motor severity (UPDRS Part III score) were related to verbal memory changes. Methods A consecutive group of 40 patients undergoing bilateral Subthalamic Nucleus (STN)-DBS for PD were selected. Brain MRI data was acquired, pre-processed and structural volumetric data was extracted using FSL. Verbal memory test scores for pre- and post-STN-DBS surgery were recorded. Linear regression was used to investigate the relationship between score change and structural volumetric data. Results A significant relationship was demonstrated between change in List Learning test score and thalamic (left, p = 0.02) and hippocampal (left, p = 0.02 and right p = 0.03) volumes. Duration of symptoms was also associated with List Learning score change (p = 0.02 to 0.03). Conclusion Verbal memory score changes appear to have a relationship to pre-surgical MRI structural volumetric data. The findings of this study provide a basis for further research into the use of pre-surgical MRI to counsel PD patients regarding post-surgical verbal memory changes. PMID:27557088

  18. Communication among neurons.

    Science.gov (United States)

    Marner, Lisbeth

    2012-04-01

    The communication among neurons is the prerequisite for the working brain. To understand the cellular, neurochemical, and structural basis of this communication, and the impacts of aging and disease on brain function, quantitative measures are necessary. This thesis evaluates several quantitative neurobiological methods with respect to possible bias and methodological issues. Stereological methods are suited for the unbiased estimation of number, length, and volumes of components of the nervous system. Stereological estimates of the total length of myelinated nerve fibers were made in white matter of post mortem brains, and the impact of aging and diseases as Schizophrenia and Alzheimer's disease were evaluated. Although stereological methods are in principle unbiased, shrinkage artifacts are difficult to account for. Positron emission tomography (PET) recordings, in conjunction with kinetic modeling, permit the quantitation of radioligand binding in brain. The novel serotonin 5-HT4 antagonist [11C]SB207145 was used as an example of the validation process for quantitative PET receptor imaging. Methods based on reference tissue as well as methods based on an arterial plasma input function were evaluated with respect to precision and accuracy. It was shown that [11C]SB207145 binding had high sensitivity to occupancy by unlabeled ligand, necessitating high specific activity in the radiosynthesis to avoid bias. The established serotonin 5-HT2A ligand [18F]altanersin was evaluated in a two-year follow-up study in elderly subjects. Application of partial volume correction of the PET data diminished the reliability of the measures, but allowed for the correct distinction between changes due to brain atrophy and receptor availability. Furthermore, a PET study of patients with Alzheimer's disease with the serotonin transporter ligand [11C]DASB showed relatively preserved serotonergic projections, despite a marked decrease in 5-HT2A receptor binding. Possible confounders are

  19. Dye-coupled magnocellular peptidergic neurons of the rat paraventricular nucleus show homotypic immunoreactivity.

    Science.gov (United States)

    Cobbett, P; Smithson, K G; Hatton, G I

    1985-12-01

    Magnocellular neurons in rat hypothalamic slices are known to exhibit dye coupling: the transfer of the fluorescent dye, Lucifer Yellow, from an intracellularly-injected neuron to one or more nearby neurons. The question of the hormonal identity of coupled cells and the possibility of dye coupling as an artefact led us to determine the immunoreactivity of dye-coupled magnocellular neurons in the paraventricular nucleus of the rat hypothalamus using antisera to oxytocin- and vasopressin-associated neurophysins. In 23 pairs, one triplet, and one quadruplet, immunoreactivity to one or the other antiserum was always exclusive, and dye coupling was always homotypic, that is, coupled neurons in each instance were reactive to the same antiserum. The quadruplet, triplet and 17 pairs were immunoreactive to vasopressin-associated neurophysin, and oxytoxin-associated neurophysin immunoreactivity was observed in the remaining pairs. Immunoreactivity to each antiserum was found for somasomatic and non somasomatic modes of coupling and for coupled neurons in the three magnocellular areas of the nucleus. A relationship between mode of coupling and hormone content was not detected. The data support the hypothesis that coupling is a real, functionally significant mechanism for coordinating neuronal activity in this nucleus, particularly under conditions of high hormone demand. They do not support the idea that coupling is artefact. The possibility of a relationship between hormone content and mode of coupling, and the projection pathway(s) of the coupled neurons of each type require further study.

  20. First report on an inotropic peptide activating tetrodotoxin-sensitive, "neuronal" sodium currents in the heart.

    Science.gov (United States)

    Kirchhof, Paulus; Tal, Tzachy; Fabritz, Larissa; Klimas, Jan; Nesher, Nir; Schulte, Jan S; Ehling, Petra; Kanyshkova, Tatayana; Budde, Thomas; Nikol, Sigrid; Fortmueller, Lisa; Stallmeyer, Birgit; Müller, Frank U; Schulze-Bahr, Eric; Schmitz, Wilhelm; Zlotkin, Eliahu; Kirchhefer, Uwe

    2015-01-01

    New therapeutic approaches to improve cardiac contractility without severe risk would improve the management of acute heart failure. Increasing systolic sodium influx can increase cardiac contractility, but most sodium channel activators have proarrhythmic effects that limit their clinical use. Here, we report the cardiac effects of a novel positive inotropic peptide isolated from the toxin of the Black Judean scorpion that activates neuronal tetrodotoxin-sensitive sodium channels. All venoms and peptides were isolated from Black Judean Scorpions (Buthotus Hottentotta) caught in the Judean Desert. The full scorpion venom increased left ventricular function in sedated mice in vivo, prolonged ventricular repolarization, and provoked ventricular arrhythmias. An inotropic peptide (BjIP) isolated from the full venom by chromatography increased cardiac contractility but did neither provoke ventricular arrhythmias nor prolong cardiac repolarization. BjIP increased intracellular calcium in ventricular cardiomyocytes and prolonged inactivation of the cardiac sodium current. Low concentrations of tetrodotoxin (200 nmol/L) abolished the effect of BjIP on calcium transients and sodium current. BjIP did not alter the function of Nav1.5, but selectively activated the brain-type sodium channels Nav1.6 or Nav1.3 in cellular electrophysiological recordings obtained from rodent thalamic slices. Nav1.3 (SCN3A) mRNA was detected in human and mouse heart tissue. Our pilot experiments suggest that selective activation of tetrodotoxin-sensitive neuronal sodium channels can safely increase cardiac contractility. As such, the peptide described here may become a lead compound for a new class of positive inotropic agents. © 2014 American Heart Association, Inc.

  1. Anatomic and Molecular Development of Corticostriatal Projection Neurons in Mice

    Science.gov (United States)

    Sohur, U. Shivraj; Padmanabhan, Hari K.; Kotchetkov, Ivan S.; Menezes, Joao R.L.; Macklis, Jeffrey D.

    2014-01-01

    Corticostriatal projection neurons (CStrPN) project from the neocortex to ipsilateral and contralateral striata to control and coordinate motor programs and movement. They are clinically important as the predominant cortical population that degenerates in Huntington's disease and corticobasal ganglionic degeneration, and their injury contributes to multiple forms of cerebral palsy. Together with their well-studied functions in motor control, these clinical connections make them a functionally, behaviorally, and clinically important population of neocortical neurons. Little is known about their development. “Intratelencephalic” CStrPN (CStrPNi), projecting to the contralateral striatum, with their axons fully within the telencephalon (intratelencephalic), are a major population of CStrPN. CStrPNi are of particular interest developmentally because they share hodological and axon guidance characteristics of both callosal projection neurons (CPN) and corticofugal projection neurons (CFuPN); CStrPNi send axons contralaterally before descending into the contralateral striatum. The relationship of CStrPNi development to that of broader CPN and CFuPN populations remains unclear; evidence suggests that CStrPNi might be evolutionary “hybrids” between CFuPN and deep layer CPN—in a sense “chimeric” with both callosal and corticofugal features. Here, we investigated the development of CStrPNi in mice—their birth, maturation, projections, and expression of molecular developmental controls over projection neuron subtype identity. PMID:23118198

  2. Neuronal histamine and cognitive symptoms in Alzheimer's disease.

    Science.gov (United States)

    Zlomuzica, Armin; Dere, Dorothea; Binder, Sonja; De Souza Silva, Maria Angelica; Huston, Joseph P; Dere, Ekrem

    2016-07-01

    Alzheimer's disease is a neurodegenerative disorder characterized by extracellular amyloid plaque deposits, mainly composed of amyloid-beta peptide and intracellular neurofibrillary tangles consisting of aggregated hyperphosphorylated tau protein. Amyloid-beta represents a neurotoxic proteolytic cleavage product of amyloid precursor protein. The progressive cognitive decline that is associated with Alzheimer's disease has been mainly attributed to a deficit in cholinergic neurotransmission due to the continuous degeneration of cholinergic neurons e.g. in the basal forebrain. There is evidence suggesting that other neurotransmitter systems including neuronal histamine also contribute to the development and maintenance of Alzheimer's disease-related cognitive deficits. Pathological changes in the neuronal histaminergic system of such patients are highly predictive of ensuing cognitive deficits. Furthermore, histamine-related drugs, including histamine 3 receptor antagonists, have been demonstrated to alleviate cognitive symptoms in Alzheimer's disease. This review summarizes findings from animal and clinical research on the relationship between the neuronal histaminergic system and cognitive deterioration in Alzheimer's disease. The significance of the neuronal histaminergic system as a promising target for the development of more effective drugs for the treatment of cognitive symptoms is discussed. Furthermore, the option to use histamine-related agents as neurogenesis-stimulating therapy that counteracts progressive brain atrophy in Alzheimer's disease is considered. This article is part of a Special Issue entitled 'Histamine Receptors'. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Varicella Zoster Virus (VZV-Human Neuron Interaction

    Directory of Open Access Journals (Sweden)

    Don Gilden

    2013-09-01

    Full Text Available Varicella zoster virus (VZV is a highly neurotropic, exclusively human herpesvirus. Primary infection causes varicella (chickenpox, wherein VZV replicates in multiple organs, particularly the skin. Widespread infection in vivo is confirmed by the ability of VZV to kill tissue culture cells in vitro derived from any organ. After varicella, VZV becomes latent in ganglionic neurons along the entire neuraxis. During latency, virus DNA replication stops, transcription is restricted, and no progeny virions are produced, indicating a unique virus-cell (neuron relationship. VZV reactivation produces zoster (shingles, often complicated by serious neurological and ocular disorders. The molecular trigger(s for reactivation, and thus the identity of a potential target to prevent it, remains unknown due to an incomplete understanding of the VZV-neuron interaction. While no in vitro system has yet recapitulated the findings in latently infected ganglia, recent studies show that VZV infection of human neurons in SCID mice and of human stem cells, including induced human pluripotent stem cells and normal human neural progenitor tissue-like assemblies, can be established in the absence of a cytopathic effect. Usefulness of these systems in discovering the mechanisms underlying reactivation awaits analyses of VZV-infected, highly pure (>90%, terminally differentiated human neurons capable of prolonged survival in vitro.

  4. Culture of Mouse Olfactory Sensory Neurons

    OpenAIRE

    Gong, Qizhi

    2012-01-01

    Olfactory sensory neurons, located in the nasal epithelium, detect and transmit odorant information to the central nervous system. This requires that these neurons form specific neuronal connections within the olfactory bulb and express receptors and signaling molecules specific for these functions. This protocol describes a primary olfactory sensory neuron culture technique that allows in vitro investigation of olfactory sensory neuron differentiation, axon outgrowth, odorant receptor expres...

  5. Specification of GnRH-1 neurons by antagonistic FGF and retinoic acid signaling.

    Science.gov (United States)

    Sabado, Virginie; Barraud, Perrine; Baker, Clare V H; Streit, Andrea

    2012-02-15

    A small population of neuroendocrine cells in the rostral hypothalamus and basal forebrain is the key regulator of vertebrate reproduction. They secrete gonadotropin-releasing hormone (GnRH-1), communicate with many areas of the brain and integrate multiple inputs to control gonad maturation, puberty and sexual behavior. In humans, disruption of the GnRH-1 system leads to hypogonadotropic gonadism and Kallmann syndrome. Unlike other neurons in the central nervous system, GnRH-1 neurons arise in the periphery, however their embryonic origin is controversial, and the molecular mechanisms that control their initial specification are not clear. Here, we provide evidence that in chick GnRH-1 neurons originate in the olfactory placode, where they are specified shortly after olfactory sensory neurons. FGF signaling is required and sufficient to induce GnRH-1 neurons, while retinoic acid represses their formation. Both pathways regulate and antagonize each other and our results suggest that the timing of signaling is critical for normal GnRH-1 neuron formation. While Kallmann's syndrome has generally been attributed to a failure of GnRH-1 neuron migration due to impaired FGF signaling, our findings suggest that in at least some Kallmann patients these neurons may never be specified. In addition, this study highlights the intimate embryonic relationship between GnRH-1 neurons and their targets and modulators in the adult. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Development of inner ear afferent connections: forming primary neurons and connecting them to the developing sensory epithelia

    Science.gov (United States)

    Fritzsch, Bernd

    2003-01-01

    The molecular and cellular origin of the primary neurons of the inner ear, the vestibular and spiral neurons, is reviewed including how they connect to the specific sensory epithelia and what the molecular nature of their survival is. Primary neurons of the ear depend on a single basic Helix-Loop-Helix (bHLH) protein for their formation, neurogenin 1 (ngn1). An immediate downstream gene is the bHLH gene neuronal differentiation (NeuroD). Targeted null mutations of ngn1 results in absence of primary neuron formation; targeted null mutation of NeuroD results in loss of almost all spiral and many vestibular neurons. NeuroD and a later expressed gene, Brn3a, play a role in pathfinding to and within sensory epithelia. The molecular nature of this pathfinding property is unknown. Reduction of hair cells in ngn1 null mutations suggests a clonal relationship with primary neurons. This relationship may play some role in specifying the identity of hair cells and the primary neurons that connect with them. Primary neuron neurites growth to sensory epithelia is initially independent of trophic factors released from developing sensory epithelia, but becomes rapidly dependent on those factors. Null mutations of specific neurotrophic factors lose distinct primary neuron populations which undergo rapid embryonic cell death.

  7. Stochastic bursting synchronization in a population of subthreshold Izhikevich neurons

    Science.gov (United States)

    Kim, Sang-Yoon; Kim, Youngnam; Hong, Duk-Geun; Kim, Jean; Lim, Woochang

    2012-05-01

    We consider a population of subthreshold Izhikevich neurons that cannot fire spontaneously without noise. As the coupling strength passes a threshold, individual neurons exhibit noise-induced burstings ( i.e., discrete groups or bursts of noise-induced spikes). We investigate stochastic bursting synchronization by varying the noise intensity. Through competition between the constructive and the destructive roles of noise, collective coherence between noise-induced burstings is found to occur over a large range of intermediate noise intensities. This kind of stochastic bursting synchronization is well characterized by using the techniques of statistical mechanics and nonlinear dynamics, such as the order parameter, the raster plot of neural spikes, the time series of the ensemble-averaged global potential, and the phase portraits of limit cycles. In contrast to spiking neurons showing only spike synchronization (characterizing a temporal relationship between spikes), bursting neurons are found to exhibit both spike synchronization and burst synchronization (characterizing a temporal relationship between the onset times of the active phases of repetitive spikings). The degree of stochastic bursting synchronization is also measured in terms of a synchronization measure that reflects the resemblance of the global potential to the individual potential.

  8. Neuronal migration abnormalities and its possible implications for schizophrenia

    Directory of Open Access Journals (Sweden)

    Kenji eTanigaki

    2015-03-01

    Full Text Available Schizophrenia is a complex mental disorder that displays behavioral deficits such as decreased sensory gating, reduced social interaction and working memory deficits. The neurodevelopmental model is one of the widely accepted hypotheses of the etiology of schizophrenia. Subtle developmental abnormalities of the brain which stated long before the onset of clinical symptoms are thought to lead to the emergence of illness. Schizophrenia has strong genetic components but its underlying molecular pathogenesis is still poorly understood. Genetic linkage and association studies have identified several genes involved in neuronal migrations as candidate susceptibility genes for schizophrenia, although their effect size is small. Recent progress in copy number variation studies also has identified much higher risk loci such as 22q11. Based on these genetic findings, we are now able to utilize genetically-defined animal models. Here we summarize the results of neurodevelopmental and behavioral analysis of genetically-defined animal models. Furthermore, animal model experiments have demonstrated that embryonic and perinatal neurodevelopmental insults in neurogenesis and neuronal migrations cause neuronal functional and behavioral deficits in affected adult animals, which are similar to those of schizophrenic patients. However, these findings do not establish causative relationship. Genetically-defined animal models are a critical approach to explore the relationship between neuronal migration abnormalities and behavioral abnormalities relevant to Schizophrenia.

  9. Purines and Neuronal Excitability: Links to the Ketogenic Diet

    Science.gov (United States)

    Masino, SA; Kawamura, M; Ruskin, DN; Geiger, JD; Boison, D

    2011-01-01

    ATP and adenosine are purines that play dual roles in cell metabolism and neuronal signaling. Acting at the A1 receptor (A1R) subtype, adenosine acts directly on neurons to inhibit excitability and is a powerful endogenous neuroprotective and anticonvulsant molecule. Previous research showed an increase in ATP and other cell energy parameters when an animal is administered a ketogenic diet, an established metabolic therapy to reduce epileptic seizures, but the relationship among purines, neuronal excitability and the ketogenic diet was unclear. Recent work in vivo and in vitro tested the specific hypothesis that adenosine acting at A1Rs is a key mechanism underlying the success of ketogenic diet therapy and yielded direct evidence linking A1Rs to the antiepileptic effects of a ketogenic diet. Specifically, an in vitro mimic of a ketogenic diet revealed an A1R-dependent metabolic autocrine hyperpolarization of hippocampal neurons. In parallel, applying the ketogenic diet in vivo to transgenic mouse models with spontaneous electrographic seizures revealed that intact A1Rs are necessary for the seizure-suppressing effects of the diet. This is the first direct in vivo evidence linking A1Rs to the antiepileptic effects of a ketogenic diet. Other predictions of the relationship between purines and the ketogenic diet are discussed. Taken together, recent research on the role of purines may offer new opportunities for metabolic therapy and insight into its underlying mechanisms. PMID:21880467

  10. Ephaptic coupling in cortical neurons

    Directory of Open Access Journals (Sweden)

    Costas Anastassiou

    2014-03-01

    Full Text Available The electrochemical processes that underlie neural function manifest themselves in ceaseless spatial and temporal fluctuations in the extracellular electric field. The local field potential (LFP, used to study neural interactions during various brain states, is regarded as an epiphenomenon of coordinated neural activity. Yet the extracellular field activity feeds back onto the electrical potential across the neuronal membrane via ephaptic coupling (Jefferys et al, Physiol Rev, 1995. The extent to which such ephaptic coupling alters the functioning of individual neurons and neural assemblies under physiological conditions has remained largely speculative despite recent advances (Ozen et al, JNeurosci, 2010; Fröhlich & McCormick, Neuron, 2010, Anastassiou et al, JNeurosci, 2010. To address this question we use a 12-pipette setup that allows independent positioning of each pipette under visual control with μm accuracy, with the flexibility of using an arbitrary number of these as patching, extracellularly stimulating or extracellular recording pipettes only a few μm away from the cell body of patched neurons (Anastassiou et al, Nat Neurosci, 2011. We stimulated in rat somatosensory cortical slices a variety of layer 5 neural types and recorded inside and outside their cell bodies while pharmacologically silencing synaptic transmission. Pyramidal cells couple to the extracellular field distinctly different from interneurons. Ephaptic coupling strength depends both on the field strength (as measured at the neuron soma as well as the spike-history of neurons. In particular, we find that ephaptic coupling strength depends both on the field strength (as measured at the cell body as well as the spike-history of neurons. How do such effects manifest themselves in vivo? We address this question through detailed large-scale simulations from thousands of biophysically realistic and interconnected neurons (Reimann, Anastassiou et al, Neuron, 2013 emulating

  11. A proof-of-principle simulation for closed-loop control based on preexisting experimental thalamic DBS-enhanced instrumental learning.

    Science.gov (United States)

    Wang, Ching-Fu; Yang, Shih-Hung; Lin, Sheng-Huang; Chen, Po-Chuan; Lo, Yu-Chun; Pan, Han-Chi; Lai, Hsin-Yi; Liao, Lun-De; Lin, Hui-Ching; Chen, Hsu-Yan; Huang, Wei-Chen; Huang, Wun-Jhu; Chen, You-Yin

    Deep brain stimulation (DBS) has been applied as an effective therapy for treating Parkinson's disease or essential tremor. Several open-loop DBS control strategies have been developed for clinical experiments, but they are limited by short battery life and inefficient therapy. Therefore, many closed-loop DBS control systems have been designed to tackle these problems by automatically adjusting the stimulation parameters via feedback from neural signals, which has been reported to reduce the power consumption. However, when the association between the biomarkers of the model and stimulation is unclear, it is difficult to develop an optimal control scheme for other DBS applications, i.e., DBS-enhanced instrumental learning. Furthermore, few studies have investigated the effect of closed-loop DBS control for cognition function, such as instrumental skill learning, and have been implemented in simulation environments. In this paper, we proposed a proof-of-principle design for a closed-loop DBS system, cognitive-enhancing DBS (ceDBS), which enhanced skill learning based on in vivo experimental data. The ceDBS acquired local field potential (LFP) signal from the thalamic central lateral (CL) nuclei of animals through a neural signal processing system. A strong coupling of the theta oscillation (4-7 Hz) and the learning period was found in the water reward-related lever-pressing learning task. Therefore, the theta-band power ratio, which was the averaged theta band to averaged total band (1-55 Hz) power ratio, could be used as a physiological marker for enhancement of instrumental skill learning. The on-line extraction of the theta-band power ratio was implemented on a field-programmable gate array (FPGA). An autoregressive with exogenous inputs (ARX)-based predictor was designed to construct a CL-thalamic DBS model and forecast the future physiological marker according to the past physiological marker and applied DBS. The prediction could further assist the design of

  12. Neuronal factors determining high intelligence.

    Science.gov (United States)

    Dicke, Ursula; Roth, Gerhard

    2016-01-05

    Many attempts have been made to correlate degrees of both animal and human intelligence with brain properties. With respect to mammals, a much-discussed trait concerns absolute and relative brain size, either uncorrected or corrected for body size. However, the correlation of both with degrees of intelligence yields large inconsistencies, because although they are regarded as the most intelligent mammals, monkeys and apes, including humans, have neither the absolutely nor the relatively largest brains. The best fit between brain traits and degrees of intelligence among mammals is reached by a combination of the number of cortical neurons, neuron packing density, interneuronal distance and axonal conduction velocity--factors that determine general information processing capacity (IPC), as reflected by general intelligence. The highest IPC is found in humans, followed by the great apes, Old World and New World monkeys. The IPC of cetaceans and elephants is much lower because of a thin cortex, low neuron packing density and low axonal conduction velocity. By contrast, corvid and psittacid birds have very small and densely packed pallial neurons and relatively many neurons, which, despite very small brain volumes, might explain their high intelligence. The evolution of a syntactical and grammatical language in humans most probably has served as an additional intelligence amplifier, which may have happened in songbirds and psittacids in a convergent manner. © 2015 The Author(s).

  13. Brain Neurons as Quantum Computers:

    Science.gov (United States)

    Bershadskii, A.; Dremencov, E.; Bershadskii, J.; Yadid, G.

    The question: whether quantum coherent states can sustain decoherence, heating and dissipation over time scales comparable to the dynamical timescales of brain neurons, has been actively discussed in the last years. A positive answer on this question is crucial, in particular, for consideration of brain neurons as quantum computers. This discussion was mainly based on theoretical arguments. In the present paper nonlinear statistical properties of the Ventral Tegmental Area (VTA) of genetically depressive limbic brain are studied in vivo on the Flinders Sensitive Line of rats (FSL). VTA plays a key role in the generation of pleasure and in the development of psychological drug addiction. We found that the FSL VTA (dopaminergic) neuron signals exhibit multifractal properties for interspike frequencies on the scales where healthy VTA dopaminergic neurons exhibit bursting activity. For high moments the observed multifractal (generalized dimensions) spectrum coincides with the generalized dimensions spectrum calculated for a spectral measure of a quantum system (so-called kicked Harper model, actively used as a model of quantum chaos). This observation can be considered as a first experimental (in vivo) indication in the favor of the quantum (at least partially) nature of brain neurons activity.

  14. Neuronal vulnerability in Parkinson's disease.

    Science.gov (United States)

    Double, Kay L

    2012-01-01

    The classic motor symptoms of Parkinson's disease result from the progressive death of dopaminergic neurons within the substantia nigra. To date the relatively selective vulnerability of this brain region is not understood. The unique feature of dopaminergic neurons of the human substantia nigra pars compacta is the presence of the polymer pigment neuromelanin which gives this region its characteristic dark colour. In the healthy brain, neuromelanin appears to play a functional role to protect neurons from oxidative load but we have shown that in the Parkinson's disease brain the pigment undergoes structural changes and is associated with aggregation of α-synuclein protein, even early in the disease process. Further, the role of the pigment as a metal binder has also been suggested to underlie the relative vulnerability of these neurons, as changes in metal levels are suggested to be associated with neurodegenerative cascades in Parkinson's disease. While most research to date has focused on the role of iron in these pathways we have recently shown that changes in copper may contribute to neuronal vulnerability in this disorder. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. APP Metabolism Regulates Tau Proteostasis in Human Cerebral Cortex Neurons

    Directory of Open Access Journals (Sweden)

    Steven Moore

    2015-05-01

    Full Text Available Accumulation of Aβ peptide fragments of the APP protein and neurofibrillary tangles of the microtubule-associated protein tau are the cellular hallmarks of Alzheimer’s disease (AD. To investigate the relationship between APP metabolism and tau protein levels and phosphorylation, we studied human-stem-cell-derived forebrain neurons with genetic forms of AD, all of which increase the release of pathogenic Aβ peptides. We identified marked increases in intracellular tau in genetic forms of AD that either mutated APP or increased its dosage, suggesting that APP metabolism is coupled to changes in tau proteostasis. Manipulating APP metabolism by β-secretase and γ-secretase inhibition, as well as γ-secretase modulation, results in specific increases and decreases in tau protein levels. These data demonstrate that APP metabolism regulates tau proteostasis and suggest that the relationship between APP processing and tau is not mediated solely through extracellular Aβ signaling to neurons.

  16. Neurons to algorithms LDRD final report.

    Energy Technology Data Exchange (ETDEWEB)

    Rothganger, Fredrick H.; Aimone, James Bradley; Warrender, Christina E.; Trumbo, Derek

    2013-09-01

    Over the last three years the Neurons to Algorithms (N2A) LDRD project teams has built infrastructure to discover computational structures in the brain. This consists of a modeling language, a tool that enables model development and simulation in that language, and initial connections with the Neuroinformatics community, a group working toward similar goals. The approach of N2A is to express large complex systems like the brain as populations of a discrete part types that have specific structural relationships with each other, along with internal and structural dynamics. Such an evolving mathematical system may be able to capture the essence of neural processing, and ultimately of thought itself. This final report is a cover for the actual products of the project: the N2A Language Specification, the N2A Application, and a journal paper summarizing our methods.

  17. Organization of the nitrergic neuronal system in the primitive bony fishes Polypterus senegalus and Erpetoichthys calabaricus (Actinopterygii: Cladistia).

    Science.gov (United States)

    López, Jesús M; Lozano, Daniel; Morona, Ruth; González, Agustín

    2016-06-15

    Cladistians are a group of basal actinopterygian fishes that constitute a good model for studying primitive brain features, most likely present in the ancestral bony fishes. The analysis of the nitrergic neurons (with the enzyme nitric oxide synthase; NOS) has helped in understanding important aspects of brain organization in all vertebrates studied. We investigated the nitrergic system of two cladistian species by means of specific antibodies against NOS and NADPH-diaphorase (NADPH-d) histochemistry, which, with the exception of the primary olfactory and terminal nerve fibers, labeled only for NADPH-d, yielded identical results. Double immunohistochemistry was conducted for simultaneous detection of NOS with tyrosine hydroxylase, choline acetyltransferase, calbindin, calretinin, and serotonin, to establish accurately the localization of the nitrergic neurons and fibers and to assess possible interactions between these neuroactive substances. The pattern of distribution in both species showed only subtle differences in the density of labeled cells. Distinct groups of NOS-immunoreactive cells were observed in pallial and subpallial areas, paraventricular region, tuberal and retromammillary hypothalamic areas, posterior tubercle, prethalamic and thalamic areas, optic tectum, torus semicircularis, mesencephalic tegmentum, interpeduncular nucleus, superior and middle reticular nuclei, magnocellular vestibular nucleus, solitary tract nucleus, nucleus medianus magnocellularis, the spinal cord and amacrine cells in the retina. Large neurons in cranial nerve sensory ganglia were also labeled. The comparison of these results with those from other vertebrates, using a neuromeric analysis, reveals a conserved pattern of organization of the nitrergic system from this primitive fish group to amniotes, including mammals. © 2015 Wiley Periodicals, Inc.

  18. Relationships among metabolic homeostasis, diet, and peripheral afferent neuron biology

    Science.gov (United States)

    It is well-established that food intake behavior and energy balance are regulated by cross-talk between peripheral organ systems and the central nervous system (CNS), for instance through the actions of peripherally-derived leptin on hindbrain and hypothalamic loci. Diet- or obesity-associated dist...

  19. REMOD: a computational tool for remodeling neuronal dendrites

    Directory of Open Access Journals (Sweden)

    Panagiotis Bozelos

    2014-05-01

    Full Text Available In recent years, several modeling studies have indicated that dendritic morphology is a key determinant of how individual neurons acquire a unique signal processing profile. The highly branched dendritic structure that originates from the cell body, explores the surrounding 3D space in a fractal-like manner, until it reaches a certain amount of complexity. Its shape undergoes significant alterations not only in various neuropathological conditions, but in physiological, too. Yet, despite the profound effect that these alterations can have on neuronal function, the causal relationship between structure and function remains largely elusive. The lack of a systematic approach for remodeling neuronal cells and their dendritic trees is a key limitation that contributes to this problem. In this context, we developed a computational tool that allows the remodeling of any type of neurons, given a set of exemplar morphologies. The tool is written in Python and provides a simple GUI that guides the user through various options to manipulate selected neuronal morphologies. It provides the ability to load one or more morphology files (.swc or .hoc and choose specific dendrites to operate one of the following actions: shrink, remove, extend or branch (as shown in Figure 1. The user retains complete control over the extent of each alteration and if a chosen action is not possible due to pre-existing structural constraints, appropriate warnings are produced. Importantly, the tool can also be used to extract morphology statistics for one or multiple morphologies, including features such as the total dendritic length, path length to the root, branch order, diameter tapering, etc. Finally, an experimental utility enables the user to remodel entire dendritic trees based on preloaded statistics from a database of cell-type specific neuronal morphologies. To our knowledge, this is the first tool that allows (a the remodeling of existing –as opposed to the de novo

  20. Prospective Coding by Spiking Neurons.

    Directory of Open Access Journals (Sweden)

    Johanni Brea

    2016-06-01

    Full Text Available Animals learn to make predictions, such as associating the sound of a bell with upcoming feeding or predicting a movement that a motor command is eliciting. How predictions are realized on the neuronal level and what plasticity rule underlies their learning is not well understood. Here we propose a biologically plausible synaptic plasticity rule to learn predictions on a single neuron level on a timescale of seconds. The learning rule allows a spiking two-compartment neuron to match its current firing rate to its own expected future discounted firing rate. For instance, if an originally neutral event is repeatedly followed by an event that elevates the firing rate of a neuron, the originally neutral event will eventually also elevate the neuron's firing rate. The plasticity rule is a form of spike timing dependent plasticity in which a presynaptic spike followed by a postsynaptic spike leads to potentiation. Even if the plasticity window has a width of 20 milliseconds, associations on the time scale of seconds can be learned. We illustrate prospective coding with three examples: learning to predict a time varying input, learning to predict the next stimulus in a delayed paired-associate task and learning with a recurrent network to reproduce a temporally compressed version of a sequence. We discuss the potential role of the learning mechanism in classical trace conditioning. In the special case that the signal to be predicted encodes reward, the neuron learns to predict the discounted future reward and learning is closely related to the temporal difference learning algorithm TD(λ.

  1. Bifurcation analysis of the regulation of nociceptive neuronal activity

    Science.gov (United States)

    Dik, O. E.

    2017-11-01

    A model of the membrane of a nociceptive neuron from a rat dorsal ganglion has been used to address the problem of analyzing the regulation of nociceptive signals by 5-hydroxy-γ-pyrone-2-carboxylic acid, which is the active pharmaceutic ingredient of the analgesic Anoceptin. The study has applied bifurcation analysis to report the relationship between the values of model parameters and the type of problem solution before and after the parameters change in response to analgesic modulation.

  2. Copying and evolution of neuronal topology.

    Directory of Open Access Journals (Sweden)

    Chrisantha Fernando

    Full Text Available We propose a mechanism for copying of neuronal networks that is of considerable interest for neuroscience for it suggests a neuronal basis for causal inference, function copying, and natural selection within the human brain. To date, no model of neuronal topology copying exists. We present three increasingly sophisticated mechanisms to demonstrate how topographic map formation coupled with Spike-Time Dependent Plasticity (STDP can copy neuronal topology motifs. Fidelity is improved by error correction and activity-reverberation limitation. The high-fidelity topology-copying operator is used to evolve neuronal topologies. Possible roles for neuronal natural selection are discussed.

  3. Neuronal involvement in cisplatin neuropathy

    DEFF Research Database (Denmark)

    Krarup-Hansen, A; Helweg-Larsen, Susanne Elisabeth; Schmalbruch, H

    2007-01-01

    Although it is well known that cisplatin causes a sensory neuropathy, the primary site of involvement is not established. The clinical symptoms localized in a stocking-glove distribution may be explained by a length dependent neuronopathy or by a distal axonopathy. To study whether the whole neuron...... of large dorsal root ganglion cells. Motor conduction studies, autonomic function and warm and cold temperature sensation remained unchanged at all doses of cisplatin treatment. The results of these studies are consistent with degeneration of large sensory neurons whereas there was no evidence of distal...

  4. Neuronal coherence and its functional role in communication between neurons

    NARCIS (Netherlands)

    Zeitler-Geurds, M.

    2010-01-01

    Neuronal oscillations are observed in many brain areas in various frequency bands. Each of the frequency bands is associated with a particular functional role. Gamma oscillations (30-80 Hz) are thought to be related to cognitive tasks like memory and attention and possibly also involved in the

  5. One-pass deep brain stimulation of dentato-rubro-thalamic tract and subthalamic nucleus for tremor-dominant or equivalent type Parkinson's disease.

    Science.gov (United States)

    Coenen, Volker Arnd; Rijntjes, Michel; Prokop, Thomas; Piroth, Tobias; Amtage, Florian; Urbach, Horst; Reinacher, Peter Christoph

    2016-04-01

    Refractory tremor in tremor-dominant (TD) or equivalent-type (EQT) idiopathic Parkinson's syndrome (IPS) poses the challenge of choosing the best target region to for deep brain stimulation (DBS). While the subthalamic nucleus is typically chosen in younger patients as the target for dopamine-responsive motor symptoms, it is more complicated if tremor does not (fully) respond under trial conditions. In this report, we present the first results from simultaneous bilateral DBS of the DRT (dentato-rubro-thalamic tract) and the subthalamic nucleus (STN) in two elderly patients with EQT and TD IPS and dopamine-refractory tremor. Two patients received bilateral octopolar DBS electrodes in the STN additionally traversing the DRT region. Achieved electrode positions were determined with helical CT, overlaid onto DTI tractography data, and compared with clinical data of stimulation response. Both patients showed immediate and sustained improvement of their tremor, bilaterally. The proposed approach appears to be safe and feasible and a combined stimulation of the two target regions was performed tailored to the patients' symptoms. Clinically, no neuropsychiatric effects were seen. Our pilot data suggest a viable therapeutic option to treat the subgroup of TD and EQT IPS and with tremor as the predominant symptom. A clinical study to further investigate this approach ( www.clinicaltrials.gov ; NCT02288468) is the focus of our ongoing research.

  6. The Emotional Gatekeeper: A Computational Model of Attentional Selection and Suppression through the Pathway from the Amygdala to the Inhibitory Thalamic Reticular Nucleus

    Science.gov (United States)

    Bullock, Daniel; Barbas, Helen

    2016-01-01

    In a complex environment that contains both opportunities and threats, it is important for an organism to flexibly direct attention based on current events and prior plans. The amygdala, the hub of the brain's emotional system, is involved in forming and signaling affective associations between stimuli and their consequences. The inhibitory thalamic reticular nucleus (TRN) is a hub of the attentional system that gates thalamo-cortical signaling. In the primate brain, a recently discovered pathway from the amygdala sends robust projections to TRN. Here we used computational modeling to demonstrate how the amygdala-TRN pathway, embedded in a wider neural circuit, can mediate selective attention guided by emotions. Our Emotional Gatekeeper model demonstrates how this circuit enables focused top-down, and flexible bottom-up, allocation of attention. The model suggests that the amygdala-TRN projection can serve as a unique mechanism for emotion-guided selection of signals sent to cortex for further processing. This inhibitory selection mechanism can mediate a powerful affective ‘framing’ effect that may lead to biased decision-making in highly charged emotional situations. The model also supports the idea that the amygdala can serve as a relevance detection system. Further, the model demonstrates how abnormal top-down drive and dysregulated local inhibition in the amygdala and in the cortex can contribute to the attentional symptoms that accompany several neuropsychiatric disorders. PMID:26828203

  7. Striatal dopamine D2 receptor availability predicts the thalamic and medial prefrontal responses to reward in cocaine abusers three years later

    Energy Technology Data Exchange (ETDEWEB)

    Asensio, S.; Goldstein, R.; Asensio, S.; Romero, M.J.; Romero, F.J.; Wong, C.T.; Alia-Klein, N.; Tomasi, D.; Wang, G.-J.; Telang, F..; Volkow, N.D.; Goldstein, R.Z.

    2010-05-01

    Low levels of dopamine (DA) D2 receptor availability at a resting baseline have been previously reported in drug addicted individuals and have been associated with reduced ventral and dorsal prefrontal metabolism. The reduction in DA D2 receptor availability along with the reduced ventral frontal metabolism is thought to underlie compromised sensitivity to nondrug reward, a core characteristic of drug addiction. We therefore hypothesized that variability in DA D2 receptor availability at baseline will covary with dynamic responses to monetary reward in addicted individuals. Striatal DA D2 receptor availability was measured with [{sup 11}C]raclopride and positron emission tomography and response to monetary reward was measured (an average of three years later) with functional magnetic resonance imaging in seven cocaine-addicted individuals. Results show that low DA D2 receptor availability in the dorsal striatum was associated with decreased thalamic response to monetary reward; while low availability in ventral striatum was associated with increased medial prefrontal (Brodmann Area 6/8/32) response to monetary reward. These preliminary results, that need to be replicated in larger sample sizes and validated with healthy controls, suggest that resting striatal DA D2 receptor availability predicts variability in functional responses to a nondrug reinforcer (money) in prefrontal cortex, implicated in behavioral monitoring, and in thalamus, implicated in conditioned responses and expectation, in cocaine-addicted individuals.

  8. Striatal dopamine D2 receptor availability predicts the thalamic and medial prefrontal responses to reward in cocaine abusers three years later

    Science.gov (United States)

    Asensio, Samuel; Romero, Maria J.; Romero, Francisco J.; Wong, Christopher; Alia-Klein, Nelly; Tomasi, Dardo; Wang, Gene-Jack; Telang, Frank; Volkow, Nora D.; Goldstein, Rita Z.

    2009-01-01

    Low levels of dopamine (DA) D2 receptor availability at a resting baseline have been previously reported in drug addicted individuals and have been associated with reduced ventral and dorsal prefrontal metabolism. The reduction in DA D2 receptor availability along with the reduced ventral frontal metabolism is thought to underlie compromised sensitivity to non-drug reward, a core characteristic of drug addiction. We therefore hypothesized that variability in DA D2 receptor availability at baseline will covary with dynamic responses to monetary reward in addicted individuals. Striatal DA D2 receptor availability was measured with [11C]raclopride and positron emission tomography and response to monetary reward was measured (an average of 3 years later) with functional magnetic resonance imaging in seven cocaine addicted individuals. Results show that low DA D2 receptor availability in the dorsal striatum was associated with decreased thalamic response to monetary reward; while low availability in ventral striatum was associated with increased medial prefrontal (Brodmann Area 6/8/32) response to monetary reward. These preliminary results, that need to be replicated in larger sample sizes and validated with healthy controls, suggest that resting striatal DA D2 receptor availability predicts variability in functional responses to a non-drug reinforcer (money) in prefrontal cortex, implicated in behavioral monitoring, and in thalamus, implicated in conditioned responses and expectation, in cocaine addicted individuals. PMID:20034014

  9. Dorsal-to-Ventral Shift in Midbrain Dopaminergic Projections and Increased Thalamic/Raphe Serotonergic Function in Early Parkinson Disease.

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    Joutsa, Juho; Johansson, Jarkko; Seppänen, Marko; Noponen, Tommi; Kaasinen, Valtteri

    2015-07-01

    Loss of nigrostriatal neurons leading to dopamine depletion in the dorsal striatum is the pathologic hallmark of Parkinson disease contributing to the primary motor symptoms of the disease. However, Parkinson pathology is more widespread in the brain, affecting also other dopaminergic pathways and neurotransmitter systems, but these changes are less well characterized. This study aimed to investigate the mesencephalic striatal and extrastriatal dopaminergic projections together with extrastriatal serotonin transporter binding in Parkinson disease. Two hundred sixteen patients with Parkinson disease and 204 control patients (patients without neurodegenerative parkinsonism syndromes and normal SPECT imaging) were investigated with SPECT using the dopamine/serotonin transporter ligand (123)I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane ((123)I-FP-CIT) in the clinical setting. The group differences and midbrain correlations were analyzed voxel by voxel over the entire brain. We found that Parkinson patients had lower (123)I-FP-CIT uptake in the striatum and ventral midbrain but higher uptake in the thalamus and raphe nuclei than control patients. In patients with Parkinson disease, the correlation of the midbrain tracer uptake was shifted from the putamen to widespread corticolimbic areas. All findings were highly significant at the voxel level familywise error-corrected P value of less than 0.05. Our findings show that Parkinson disease is associated not only with the degeneration of the nigrostriatal dopamine neurotransmission, but also with a parallel shift toward mesolimbic and mesocortical function. Furthermore, Parkinson disease patients seem to have upregulation of brain serotonin transporter function at the early phase of the disease. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  10. Characterization of cutaneous and articular sensory neurons.

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    da Silva Serra, Ines; Husson, Zoé; Bartlett, Jonathan D; Smith, Ewan St John

    2016-01-01

    A wide range of stimuli can activate sensory neurons and neurons innervating specific tissues often have distinct properties. Here, we used retrograde tracing to identify sensory neurons innervating the hind paw skin (cutaneous) and ankle/knee joints (articular), and combined immunohistochemistry and electrophysiology analysis to determine the neurochemical phenotype of cutaneous and articular neurons, as well as their electrical and chemical excitability. Immunohistochemistry analysis using RetroBeads as a retrograde tracer confirmed previous data that cutaneous and articular neurons are a mixture of myelinated and unmyelinated neurons, and the majority of both populations are peptidergic. In whole-cell patch-clamp recordings from cultured dorsal root ganglion neurons, voltage-gated inward currents and action potential parameters were largely similar between articular and cutaneous neurons, although cutaneous neuron action potentials had a longer half-peak duration (HPD). An assessment of chemical sensitivity showed that all neurons responded to a pH 5.0 solution, but that acid-sensing ion channel (ASIC) currents, determined by inhibition with the nonselective acid-sensing ion channel antagonist benzamil, were of a greater magnitude in cutaneous compared to articular neurons. Forty to fifty percent of cutaneous and articular neurons responded to capsaicin, cinnamaldehyde, and menthol, indicating similar expression levels of transient receptor potential vanilloid 1 (TRPV1), transient receptor potential ankyrin 1 (TRPA1), and transient receptor potential melastatin 8 (TRPM8), respectively. By contrast, significantly more articular neurons responded to ATP than cutaneous neurons. This work makes a detailed characterization of cutaneous and articular sensory neurons and highlights the importance of making recordings from identified neuronal populations: sensory neurons innervating different tissues have subtly different properties, possibly reflecting different

  11. A new organellar complex in rat sympathetic neurons.

    Directory of Open Access Journals (Sweden)

    Matt S Ramer

    Full Text Available Membranous compartments of neurons such as axons, dendrites and modified primary cilia are defining features of neuronal phenotype. This is unlike organelles deep to the plasma membrane, which are for the most part generic and not related directly to morphological, neurochemical or functional specializations. However, here we use multi-label immunohistochemistry combined with confocal and electron microscopy to identify a very large (approximately 6 microns in diameter, entirely intracellular neuronal organelle which occurs singly in a ubiquitous but neurochemically distinct and morphologically simple subset of sympathetic ganglion neurons. Although usually toroidal, it also occurs as twists or rods depending on its intracellular position: tori are most often perinuclear whereas rods are often found in axons. These 'loukoumasomes' (doughnut-like bodies bind a monoclonal antibody raised against beta-III-tubulin (SDL.3D10, although their inability to bind other beta-III-tubulin monoclonal antibodies indicate that the responsible antigen is not known. Position-morphology relationships within neurons and their expression of non-muscle heavy chain myosin suggest a dynamic structure. They associate with nematosomes, enigmatic nucleolus-like organelles present in many neural and non-neural tissues, which we now show to be composed of filamentous actin. Loukoumasomes also separately interact with mother centrioles forming the basal body of primary cilia. They express gamma tubulin, a microtubule nucleator which localizes to non-neuronal centrosomes, and cenexin, a mother centriole-associated protein required for ciliogenesis. These data reveal a hitherto undescribed organelle, and depict it as an intracellular transport machine, shuttling material between the primary cilium, the nematosome, and the axon.

  12. Differentiation of mouse embryonic stem cells into a defined neuronal lineage.

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    Bibel, Miriam; Richter, Jens; Schrenk, Katrin; Tucker, Kerry Lee; Staiger, Volker; Korte, Martin; Goetz, Magdalena; Barde, Yves-Alain

    2004-09-01

    Although it has long been known that cultured embryonic stem cells can generate neurons, the lineage relationships with their immediate precursors remain unclear. We report here that selection of highly proliferative stem cells followed by treatment with retinoic acid generated essentially pure precursors that markers identified as Pax-6-positive radial glial cells. As they do in vivo, these cells went on to generate neurons with remarkably uniform biochemical and electrophysiological characteristics.

  13. Cellular scaling rules for the brain of Artiodactyla include a highly folded cortex with few neurons

    Science.gov (United States)

    Kazu, Rodrigo S.; Maldonado, José; Mota, Bruno; Manger, Paul R.; Herculano-Houzel, Suzana

    2014-01-01

    Quantitative analysis of the cellular composition of rodent, primate, insectivore, and afrotherian brains has shown that non-neuronal scaling rules are similar across these mammalian orders that diverged about 95 million years ago, and therefore appear to be conserved in evolution, while neuronal scaling rules appear to be free to vary in a clade-specific manner. Here we analyze the cellular scaling rules that apply to the brain of artiodactyls, a group within the order Cetartiodactyla, believed to be a relatively recent radiation from the common Eutherian ancestor. We find that artiodactyls share non-neuronal scaling rules with all groups analyzed previously. Artiodactyls share with afrotherians and rodents, but not with primates, the neuronal scaling rules that apply to the cerebral cortex and cerebellum. The neuronal scaling rules that apply to the remaining brain areas are, however, distinct in artiodactyls. Importantly, we show that the folding index of the cerebral cortex scales with the number of neurons in the cerebral cortex in distinct fashions across artiodactyls, afrotherians, rodents, and primates, such that the artiodactyl cerebral cortex is more convoluted than primate cortices of similar numbers of neurons. Our findings suggest that the scaling rules found to be shared across modern afrotherians, glires, and artiodactyls applied to the common Eutherian ancestor, such as the relationship between the mass of the cerebral cortex as a whole and its number of neurons. In turn, the distribution of neurons along the surface of the cerebral cortex, which is related to its degree of gyrification, appears to be a clade-specific characteristic. If the neuronal scaling rules for artiodactyls extend to all cetartiodactyls, we predict that the large cerebral cortex of cetaceans will still have fewer neurons than the human cerebral cortex. PMID:25429261

  14. Thyrotropin-Releasing Hormone-Containing Axons Innervate Histaminergic Neurons in the Tuberomammillary Nucleus

    Science.gov (United States)

    Sárvári, Anna; Farkas, Erzsébet; Kádár, Andrea; Zséli, Györgyi; Füzesi, Tamás; Lechan, Ronald M.; Fekete, Csaba

    2012-01-01

    Recent studies indicate that the effect of thyrotropin-releasing hormone (TRH) on the regulation of food intake may be mediated by histaminergic neurons. To elucidate the anatomical basis for a functional relationship between TRH- and histamine-synthesizing neuronal systems, double-labeling immunocytochemistry was performed on the tuberomammillary nucleus (TMN) of rats, the exclusive location of histaminergic neurons. TRH-immunoreactive (IR) innervation of the histaminergic neurons were detected in all five subnuclei (E1-5) of the TMN, but was most prominent in the E4 and E5 subnuclei where 100% of the histamine-IR neurons were contacted. The number of TRH-IR varicosities in contact with histamine-IR neurons was also greatest in the E4 and E5 subnuclei, averaging 27.0±1.2 in E4 and 7.9±0.5 in E5. Somewhat fewer histamine-IR neurons were juxtaposed by TRH-IR varicosities in E2 and E3 and contacted by 6.3 ± 0.2 and 6.8 ± 0.2 varicosities/innervated cell, respectively. The number of juxtapositions of TRH-IR axon varicosities with histamine-IR neurons was the lowest in the E1 subnucleus (85.7±0.9%; 4.0±0.2 varicosities/innervated cell). Ultrastructural analysis demonstrated that TRH-IR axons established both asymmetric and symmetric type synapses on the perikaryon and dendrites of the histamine-IR neurons, although the majority of synapses were asymmetric type. These data demonstrate that TRH neurons heavily innervate histaminergic neurons in all subdivisions of the TMN, with the densest innervation in the E4 and E5 subdivisions, and are likely to exert activating effects. PMID:23063458

  15. Systematic Three-Dimensional Coculture Rapidly Recapitulates Interactions between Human Neurons and Astrocytes

    Directory of Open Access Journals (Sweden)

    Robert Krencik

    2017-12-01

    Full Text Available Summary: Human astrocytes network with neurons in dynamic ways that are still poorly defined. Our ability to model this relationship is hampered by the lack of relevant and convenient tools to recapitulate this complex interaction. To address this barrier, we have devised efficient coculture systems utilizing 3D organoid-like spheres, termed asteroids, containing pre-differentiated human pluripotent stem cell (hPSC-derived astrocytes (hAstros combined with neurons generated from hPSC-derived neural stem cells (hNeurons or directly induced via Neurogenin 2 overexpression (iNeurons. Our systematic methods rapidly produce structurally complex hAstros and synapses in high-density coculture with iNeurons in precise numbers, allowing for improved studies of neural circuit function, disease modeling, and drug screening. We conclude that these bioengineered neural circuit model systems are reliable and scalable tools to accurately study aspects of human astrocyte-neuron functional properties while being easily ac