Motor thalamus integration of cortical, cerebellar and basal ganglia information: implications for normal and parkinsonian conditions

Motor thalamus (Mthal) is implicated in the control of movement because it is strategically located between motor areas of the cerebral cortex and motor-related subcortical structures, such as the cerebellum and basal ganglia (BG). The role of BG and cerebellum in motor control has been extensively studied but how Mthal processes inputs from these two networks is unclear. Specifically, there is considerable debate about the role of BG inputs on Mthal activity. This review summarizes anatomical and physiological knowledge of the Mthal and its afferents and reviews current theories of Mthal function by discussing the impact of cortical, BG and cerebellar inputs on Mthal activity. One view is that Mthal activity in BG and cerebellar-receiving territories is primarily “driven” by glutamatergic inputs from the cortex or cerebellum, respectively, whereas BG inputs are modulatory and do not strongly determine Mthal activity. This theory is steeped in the assumption that the Mthal processes information in the same way as sensory thalamus, through interactions of modulatory inputs with a single driver input. Another view, from BG models, is that BG exert primary control on the BG-receiving Mthal so it effectively relays information from BG to cortex. We propose a new “super-integrator” theory where each Mthal territory processes multiple driver or driver-like inputs (cortex and BG, cortex and cerebellum), which are the result of considerable integrative processing. Thus, BG and cerebellar Mthal territories assimilate motivational and proprioceptive motor information previously integrated in cortico-BG and cortico-cerebellar networks, respectively, to develop sophisticated motor signals that are transmitted in parallel pathways to cortical areas for optimal generation of motor programmes. Finally, we briefly review the pathophysiological changes that occur in the BG in parkinsonism and generate testable hypotheses about how these may affect processing of inputs in the Mthal.

[1]  F. Crick Function of the thalamic reticular complex: the searchlight hypothesis. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[2]  E. Kuramoto,et al.  Two types of thalamocortical projections from the motor thalamic nuclei of the rat: a single neuron-tracing study using viral vectors. , 2009, Cerebral cortex.

[3]  E. Olivier,et al.  Coherent oscillations in monkey motor cortex and hand muscle EMG show task‐dependent modulation , 1997, The Journal of physiology.

[4]  L. Acsády,et al.  Structural Correlates of Efficient GABAergic Transmission in the Basal Ganglia–Thalamus Pathway , 2008, The Journal of Neuroscience.

[5]  K. Kultas‐Ilinsky,et al.  Fine structure of the magnocellular subdivision of the ventral anterior thalamic nucleus (V Amc) of Macaca mulatta: II. Organization of nigrothalamic afferents as revealed with EM autoradiography , 1990, The Journal of comparative neurology.

[6]  J. Donoghue,et al.  Oscillations in local field potentials of the primate motor cortex during voluntary movement. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[7]  M. Min,et al.  A requirement of low-threshold calcium spike for induction of spike-timing-dependent plasticity at corticothalamic synapses on relay neurons in the ventrobasal nucleus of rat thalamus. , 2012, The Chinese journal of physiology.

[8]  J. Borst The low synaptic release probability in vivo , 2010, Trends in Neurosciences.

[9]  Abigail L. Person,et al.  Unitary IPSPs Drive Precise Thalamic Spiking in a Circuit Required for Learning , 2005, Neuron.

[10]  J. Deniau,et al.  Relationships between the Prefrontal Cortex and the Basal Ganglia in the Rat: Physiology of the Corticosubthalamic Circuits , 1998, The Journal of Neuroscience.

[11]  K. Kultas‐Ilinsky,et al.  Reevaluation of the primary motor cortex connections with the thalamus in primates , 2003, The Journal of comparative neurology.

[12]  E. Vaadia,et al.  Firing Patterns and Correlations of Spontaneous Discharge of Pallidal Neurons in the Normal and the Tremulous 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Vervet Model of Parkinsonism , 2000, The Journal of Neuroscience.

[13]  E. Perret,et al.  Simple and complex finger movement performance of patients with Parkinsonism before and after a unilateral stereotaxic thalamotomy. , 1970, Journal of neurology, neurosurgery, and psychiatry.

[14]  R N Lemon,et al.  Synchronization in monkey motor cortex during a precision grip task. I. Task-dependent modulation in single-unit synchrony. , 2001, Journal of neurophysiology.

[15]  J. Sutin,et al.  Locus coeruleus modulation of the motor thalamus: Inhibition in nuclei ventralis lateralis and ventralis anterior , 1981, Experimental Neurology.

[16]  F. Johnson,et al.  Induced cell death in a thalamic nucleus during a restricted period of zebra finch vocal development , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[17]  T Shibazaki,et al.  Long-term follow-up results of selective VIM-thalamotomy. , 1986, Journal of neurosurgery.

[18]  M Abeles,et al.  Activity of Pallidal and Striatal Tonically Active Neurons Is Correlated in MPTP-Treated Monkeys But Not in Normal Monkeys , 2001, The Journal of Neuroscience.

[19]  P. Strick,et al.  Basal ganglia and cerebellar loops: motor and cognitive circuits , 2000, Brain Research Reviews.

[20]  T. Klockgether,et al.  The rat ventromedial thalamic nucleus and motor control: role of N- methyl-D-aspartate-mediated excitation, GABAergic inhibition, and muscarinic transmission , 1986, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[21]  A. Graybiel,et al.  Activity of striatal neurons reflects dynamic encoding and recoding of procedural memories , 2005, Nature.

[22]  E. Bézard,et al.  From single extracellular unit recording in experimental and human Parkinsonism to the development of a functional concept of the role played by the basal ganglia in motor control , 2002, Progress in Neurobiology.

[23]  R. Guillery,et al.  On the actions that one nerve cell can have on another: distinguishing "drivers" from "modulators". , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[24]  J. Borst,et al.  How Do Short-Term Changes at Synapses Fine-Tune Information Processing? , 2012, The Journal of Neuroscience.

[25]  H. Bergman,et al.  Goal-directed and habitual control in the basal ganglia: implications for Parkinson's disease , 2010, Nature Reviews Neuroscience.

[26]  David Fan,et al.  Mechanisms of Action Selection and Timing in Substantia Nigra Neurons , 2012, The Journal of Neuroscience.

[27]  S. T. Sakai,et al.  Comparison of cerebellothalamic and pallidothalamic projections in the monkey (Macaca fuscata): A double anterograde labeling study , 1996, The Journal of comparative neurology.

[28]  R. Deichmann,et al.  The tremor network targeted by successful VIM deep brain stimulation in humans , 2012, Neurology.

[29]  Marc A Sommer,et al.  The role of the thalamus in motor control , 2003, Current Opinion in Neurobiology.

[30]  J. Kaas,et al.  The thalamic connections of motor, premotor, and prefrontal areas of cortex in a prosimian primate (Otolemur garnetti) , 2006, Neuroscience.

[31]  J. Walters,et al.  State-Dependent Spike and Local Field Synchronization between Motor Cortex and Substantia Nigra in Hemiparkinsonian Rats , 2012, The Journal of Neuroscience.

[32]  Andrea A. Kühn,et al.  Thalamic gamma oscillations correlate with reaction time in a Go/noGo task in patients with essential tremor , 2013, NeuroImage.

[33]  M. Uno,et al.  The mode of pallido-thalamic transmission investigated with intracellular recording from cat thalamus , 1978, Experimental Brain Research.

[34]  M. E. Anderson,et al.  Pallidal discharge related to the kinematics of reaching movements in two dimensions. , 1997, Journal of neurophysiology.

[35]  F. Lenz,et al.  Intraoperative microelectrode and semi‐microelectrode recording during the physiological localization of the thalamic nucleus ventral intermediate , 2002, Movement disorders : official journal of the Movement Disorder Society.

[36]  Edward A. Stern,et al.  Birdbrains could teach basal ganglia research a new song , 2005, Trends in Neurosciences.

[37]  J. Penney,et al.  The functional anatomy of basal ganglia disorders , 1989, Trends in Neurosciences.

[38]  L. Acsády,et al.  Drivers of the Primate Thalamus , 2012, The Journal of Neuroscience.

[39]  M. Horne,et al.  The relationship between monkey ventrolateral thalamic nucleus activity and kinematic parameters of wrist movement , 1996, Brain Research.

[40]  A. Parent,et al.  Contralateral pallidothalamic and pallidotegmental projections in primates: an anterograde and retrograde labeling study , 1991, Brain Research.

[41]  Anne Beuter,et al.  Modulation of tremor amplitude during deep brain stimulation at different frequencies , 2003, Brain and Cognition.

[42]  M. Mauk,et al.  What the cerebellum computes , 2003, Trends in Neurosciences.

[43]  C. McIntyre,et al.  Basal ganglia activity patterns in parkinsonism and computational modeling of their downstream effects , 2012, The European journal of neuroscience.

[44]  A. Nambu,et al.  Movement-related activity of thalamic neurons with input from the globus pallidus and projection to the motor cortex in the monkey , 2004, Experimental Brain Research.

[45]  A. Oliviero,et al.  Dopamine Dependency of Oscillations between Subthalamic Nucleus and Pallidum in Parkinson's Disease , 2001, The Journal of Neuroscience.

[46]  Michale S Fee,et al.  Integration of cortical and pallidal inputs in the basal ganglia-recipient thalamus of singing birds. , 2012, Journal of neurophysiology.

[47]  F. J. Gillingham,et al.  The long-term results of stereotaxic surgery and L-dopa therapy in patients with Parkinson's disease. A 10-year follow-up study. , 1980, Journal of neurosurgery.

[48]  M. Sirota,et al.  Activity of Different Classes of Neurons of the Motor Cortex during Locomotion , 2003, The Journal of Neuroscience.

[49]  D James Surmeier,et al.  Enhancement of Excitatory Synaptic Integration by GABAergic Inhibition in the Subthalamic Nucleus , 2005, The Journal of Neuroscience.

[50]  H Mushiake,et al.  Pallidal neuron activity during sequential arm movements. , 1995, Journal of neurophysiology.

[51]  H. Bergman,et al.  Lack of spike-count and spike-time correlations in the substantia nigra reticulata despite overlap of neural responses. , 2007, Journal of neurophysiology.

[52]  J. Rawson,et al.  Projections from the lateral and interposed cerebellar nuclei to the thalamus of the rat: A light and electron microscopic study using single and double anterograde labelling , 1994, The Journal of comparative neurology.

[53]  V. Prokopenko,et al.  Electrophysiological investigation of thalamic neuronal mechanisms of motor disorders in parkinsonism: an influence of D2ergic transmission blockade on excitation and inhibition of relay neurons in motor thalamic nuclei of cat , 1994, Neuroscience.

[54]  H. Bergman,et al.  Information processing, dimensionality reduction and reinforcement learning in the basal ganglia , 2003, Progress in Neurobiology.

[55]  P. Brown,et al.  Gamma activity and reactivity in human thalamic local field potentials , 2009, The European journal of neuroscience.

[56]  Atsushi Nambu,et al.  Globus pallidus internal segment. , 2007, Progress in brain research.

[57]  J. Dostrovsky,et al.  Movement-related neurons of the subthalamic nucleus in patients with Parkinson disease. , 2002, Journal of neurosurgery.

[58]  Hideki Oshima,et al.  Deep brain stimulation for the treatment of parkinsonian, essential, and poststroke tremor: a suitable stimulation method and changes in effective stimulation intensity. , 2004, Journal of neurosurgery.

[59]  Sara Marceglia,et al.  The effects of levodopa and ongoing deep brain stimulation on subthalamic beta oscillations in Parkinson's disease , 2010, Experimental Neurology.

[60]  R W Guillery,et al.  Distinct functions for direct and transthalamic corticocortical connections. , 2011, Journal of neurophysiology.

[61]  A. Reiner,et al.  Evidence for a possible avian dorsal thalamic region comparable to the mammalian ventral anterior, ventral lateral, and oral ventroposterolateral nuclei , 1997, The Journal of comparative neurology.

[62]  J. Eccles The cerebellum as a computer: patterns in space and time. , 1973, The Journal of physiology.

[63]  Christian Lüscher,et al.  Group 1 mGluR-Dependent Synaptic Long-Term Depression: Mechanisms and Implications for Circuitry and Disease , 2010, Neuron.

[64]  J. Dostrovsky,et al.  Dependence of subthalamic nucleus oscillations on movement and dopamine in Parkinson's disease. , 2002, Brain : a journal of neurology.

[65]  G Mann,et al.  ON THE THALAMUS * , 1905, British medical journal.

[66]  R. Turner,et al.  Primary motor cortex of the parkinsonian monkey: differential effects on the spontaneous activity of pyramidal tract-type neurons. , 2011, Cerebral cortex.

[67]  R. Luján Exploring the Thalamus and its Role in Cortical Function, S.M. Sherman, R.W. Guillery (Eds.). The MIT Press (2006), ISBN: 0-262-19532-1 , 2007 .

[68]  D. Perkel,et al.  Long‐range GABAergic projection in a circuit essential for vocal learning , 1999, The Journal of comparative neurology.

[69]  J. Caston,et al.  Effects of ventrolateral-ventromedial thalamic lesions on motor coordination and spatial orientation in rats , 2003, Neuroscience Research.

[70]  Y. Shinoda,et al.  Thalamic terminal morphology and distribution of single corticothalamic axons originating from layers 5 and 6 of the cat motor cortex , 2001, The Journal of comparative neurology.

[71]  M. Farrant,et al.  Variations on an inhibitory theme: phasic and tonic activation of GABAA receptors , 2005, Nature Reviews Neuroscience.

[72]  R. Hassler Striatal control of locomotion, intentional actions and of integrating and perceptive activity , 1978, Journal of the Neurological Sciences.

[73]  W. Regehr,et al.  Short-term synaptic plasticity. , 2002, Annual review of physiology.

[74]  A. Georgopoulos Neural integration of movement: role of motor cortex in reaching , 1988, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[75]  R. Hassler,et al.  A Special Method of Stereotactic Brain Operation , 1955, Proceedings of the Royal Society of Medicine.

[76]  R. Llinás,et al.  Electrophysiological properties of guinea‐pig thalamic neurones: an in vitro study. , 1984, The Journal of physiology.

[77]  W T Thach,et al.  The cerebellum and the adaptive coordination of movement. , 1992, Annual review of neuroscience.

[78]  P. Brown,et al.  Dopamine depletion increases the power and coherence of β‐oscillations in the cerebral cortex and subthalamic nucleus of the awake rat , 2005, The European journal of neuroscience.

[79]  S. Hughes,et al.  The slow (<1 Hz) rhythm of non-REM sleep: a dialogue between three cardinal oscillators , 2010, Nature Neuroscience.

[80]  J. Obeso,et al.  Pathophysiology of the basal ganglia in Parkinson's disease , 2000, Trends in Neurosciences.

[81]  P. Strick,et al.  Preferential activity of dentate neurons during limb movements guided by vision. , 1993, Journal of neurophysiology.

[82]  R. Llinás,et al.  Ionic basis for the electro‐responsiveness and oscillatory properties of guinea‐pig thalamic neurones in vitro. , 1984, The Journal of physiology.

[83]  Etienne Perretv Simple motor performance of patients with Parkinson's disease before and after a surgical lesion in the thalamus. , 1968, Journal of neurology, neurosurgery, and psychiatry.

[84]  O Hikosaka,et al.  GABAergic output of the basal ganglia. , 2007, Progress in brain research.

[85]  F. Lenz,et al.  Patterns of bursting occurring in thalamic cells during parkinsonian tremor , 1998, Neuroscience.

[86]  Zhiping P. Pang,et al.  Distinct Neuronal Coding Schemes in Memory Revealed by Selective Erasure of Fast Synchronous Synaptic Transmission , 2012, Neuron.

[87]  G Oakson,et al.  Physiological characteristics of anterior thalamic nuclei, a group devoid of inputs from reticular thalamic nucleus. , 1987, Journal of neurophysiology.

[88]  Neural activity in the monkey anterior ventrolateral thalamus during trained, ballistic movements. , 1993, Journal of neurophysiology.

[89]  A. Morel,et al.  The dual pattern of corticothalamic projection of the premotor cortex in macaque monkeys , 2003 .

[90]  A. Nambu,et al.  Discharge patterns of pallidal neurons with input from various cortical areas during movement in the monkey , 1990, Brain Research.

[91]  F. Horak,et al.  Influence of globus pallidus on arm movements in monkeys. II. Effects of stimulation. , 1984, Journal of neurophysiology.

[92]  M. E. Anderson,et al.  Activity of neurons in cerebellar-receiving and pallidal-receiving areas of the thalamus of the behaving monkey. , 1991, Journal of neurophysiology.

[93]  A. Benabid,et al.  Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus , 1991, The Lancet.

[94]  Tomoki Fukai,et al.  Microcircuitry coordination of cortical motor information in self-initiation of voluntary movements , 2009, Nature Neuroscience.

[95]  J. Tepper,et al.  Cerebellar-responsive neurons in the thalamic ventroanterior-ventrolateral complex of rats: Light and electron microscopy , 1994, Neuroscience.

[96]  M. Horne,et al.  Cerebellar thalamic activity in the macaque monkey encodes the duration but not the force or velocity of wrist movement , 2005, Brain Research.

[97]  M. Delong,et al.  Activity of pallidal neurons during movement. , 1971, Journal of neurophysiology.

[98]  Angelo Antonini,et al.  Parkinson's disease tremor-related metabolic network: Characterization, progression, and treatment effects , 2011, NeuroImage.

[99]  J. Jankovic,et al.  Long-term evaluation of deep brain stimulation of the thalamus. , 2006, Journal of neurosurgery.

[100]  M. Steriade Grouping of brain rhythms in corticothalamic systems , 2006, Neuroscience.

[101]  W. J. Brown,et al.  Stereotaxic lesions in Parkinson's disease. Clinicopathological correlations. , 1966, Archives of neurology.

[102]  B. Hyland,et al.  Bradykinesia Induced by Dopamine D2 Receptor Blockade Is Associated with Reduced Motor Cortex Activity in the Rat , 2005, The Journal of Neuroscience.

[103]  M. Uno,et al.  The mode of cerebello-thalamic relay transmission investigated with intracellular recording from cells of the ventrolateral nucleus of cat's thalamus , 2004, Experimental Brain Research.

[104]  M. Anderson,et al.  An analysis of potentially converging inputs to the rostral ventral thalamic nuclei of the cat , 2004, Experimental Brain Research.

[105]  Michale S. Fee,et al.  A cortical motor nucleus drives the basal ganglia-recipient thalamus in singing birds , 2012, Nature Neuroscience.

[106]  Abigail L. Person,et al.  Pallidal Neuron Activity Increases during Sensory Relay through Thalamus in a Songbird Circuit Essential for Learning , 2007, The Journal of Neuroscience.

[107]  J. Dostrovsky,et al.  Surgery of the motor thalamus: Problems with the present nomenclatures , 2002, Movement disorders : official journal of the Movement Disorder Society.

[108]  E G Butler,et al.  The activity of monkey thalamic and motor cortical neurones in a skilled, ballistic movement. , 1992, The Journal of physiology.

[109]  Tetsuro Yamamoto,et al.  Intracellular recordings from rat thalamic VL neurons: a study combined with intracellular staining , 2004, Experimental Brain Research.

[110]  J. Yelnik,et al.  Thalamic stimulation for tremor: Can target determination be improved? , 2011, Movement disorders : official journal of the Movement Disorder Society.

[111]  A. Doupe,et al.  Activity Propagation in an Avian Basal Ganglia-Thalamocortical Circuit Essential for Vocal Learning , 2009, The Journal of Neuroscience.

[112]  D. McCormick,et al.  A model of the electrophysiological properties of thalamocortical relay neurons. , 1992, Journal of neurophysiology.

[113]  Minmin Luo,et al.  A GABAergic, Strongly Inhibitory Projection to a Thalamic Nucleus in the Zebra Finch Song System , 1999, The Journal of Neuroscience.

[114]  E. D’Angelo,et al.  The cerebellar network: From structure to function and dynamics , 2011, Brain Research Reviews.

[115]  M. D. Crutcher,et al.  Relations between parameters of step-tracking movements and single cell discharge in the globus pallidus and subthalamic nucleus of the behaving monkey , 1983, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[116]  J. Murphy,et al.  Cross-correlation analysis of thalamic neurons and EMG activity in parkinsonian tremor. , 1985, Applied neurophysiology.

[117]  T. Sejnowski,et al.  Reliability of spike timing in neocortical neurons. , 1995, Science.

[118]  Kiyoshi Kurata,et al.  Activity properties and location of neurons in the motor thalamus that project to the cortical motor areas in monkeys. , 2005, Journal of neurophysiology.

[119]  Laurentiu S. Popa,et al.  What Features of Limb Movements are Encoded in the Discharge of Cerebellar Neurons? , 2011, The Cerebellum.

[120]  A. P. Georgopoulos,et al.  Cortical mechanisms related to the direction of two-dimensional arm movements: relations in parietal area 5 and comparison with motor cortex , 1983, Experimental Brain Research.

[121]  L. Hazrati,et al.  Substantia nigra pars reticulata projects to the reticular thalamic nucleus of the cat: a morphological and electrophysiological study , 1990, Brain Research.

[122]  J. Deniau,et al.  Disinhibition as a basic process in the expression of striatal functions , 1990, Trends in Neurosciences.

[123]  T. Klockgether,et al.  Motor actions of excitatory amino acids and their antagonists within the rat ventromedial thalamic nucleus , 1986, Brain Research.

[124]  L. Tremblay,et al.  Abnormal influences of passive limb movement on the activity of globus pallidus neurons in parkinsonian monkeys , 1988, Brain Research.

[125]  E. Bézard,et al.  Electrophysiological and metabolic evidence that high‐frequency stimulation of the subthalamic nucleus bridles neuronal activity in the subthalamic nucleus and the substantia nigra reticulata , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[126]  C. Marsden,et al.  Stereotactic thalamotomy in tremor‐dominant Parkinson's disease: An H215O PET motor activation study , 1997, Annals of neurology.

[127]  M. Nicolelis,et al.  Subcortical Neuronal Ensembles: An Analysis of Motor Task Association, Tremor, Oscillations, and Synchrony in Human Patients , 2012, The Journal of Neuroscience.

[128]  M. Horne,et al.  The role of the cerebello-thalamo-cortical pathway in skilled movement , 1995, Progress in Neurobiology.

[129]  L. Tremblay,et al.  Thalamic Neuronal Activity in Dopamine-Depleted Primates: Evidence for a Loss of Functional Segregation within Basal Ganglia Circuits , 2005, The Journal of Neuroscience.

[130]  J. Schneider,et al.  Alterations in intralaminar and motor thalamic physiology following nigrostriatal dopamine depletion , 1996, Brain Research.

[131]  Ann M. Graybiel,et al.  Effects of Dopamine Depletion on Lfp Oscillations in Striatum Are Task-and Learning-dependent and Selectively Reversed by L-dopa Accessed Terms of Use Detailed Terms , 2022 .

[132]  A. Nambu A new dynamic model of the cortico-basal ganglia loop. , 2004, Progress in brain research.

[133]  W. T. Thach,et al.  Basal ganglia motor control. II. Late pallidal timing relative to movement onset and inconsistent pallidal coding of movement parameters. , 1991, Journal of neurophysiology.

[134]  Bryan M. Hooks,et al.  Organization of Cortical and Thalamic Input to Pyramidal Neurons in Mouse Motor Cortex , 2013, The Journal of Neuroscience.

[135]  J. Caston,et al.  Effects of centrolateral or medial thalamic lesions on motor coordination and spatial orientation in rats , 2000, Neuroscience Research.

[136]  D. Hubel,et al.  Integrative action in the cat's lateral geniculate body , 1961, The Journal of physiology.

[137]  G. Chiara,et al.  Role of thalamic γ-aminobutyrate in motor functions: Catalepsy and ipsiversive turning after intrathalamic muscimol , 1979, Neuroscience.

[138]  H. Bergman,et al.  Neurons in the globus pallidus do not show correlated activity in the normal monkey, but phase-locked oscillations appear in the MPTP model of parkinsonism. , 1995, Journal of neurophysiology.

[139]  Guillermo Paradiso,et al.  Involvement of human thalamus in the preparation of self-paced movement. , 2004, Brain : a journal of neurology.

[140]  T. Wichmann,et al.  Neuronal activity in the primate substantia nigra pars reticulata during the performance of simple and memory-guided elbow movements. , 2004, Journal of neurophysiology.

[141]  M. E. Anderson,et al.  Axonal branching patterns and location of nigrothalamic and nigrocollicular neurons in the cat. , 1980, Journal of neurophysiology.

[142]  R Porter,et al.  The discharges during movement of cells in the ventrolateral thalamus of the conscious monkey. , 1980, The Journal of physiology.

[143]  Tero Viitanen,et al.  The K+–Cl− cotransporter KCC2 promotes GABAergic excitation in the mature rat hippocampus , 2010, The Journal of physiology.

[144]  G. E. Alexander,et al.  Physiologic properties and somatotopic organization of the primate motor thalamus. , 1994, Journal of neurophysiology.

[145]  S Murray Sherman,et al.  Detectability of Excitatory versus Inhibitory Drive in an Integrate-and-Fire-or-Burst Thalamocortical Relay Neuron Model , 2002, The Journal of Neuroscience.

[146]  S. Haber,et al.  Enhanced Synchrony among Primary Motor Cortex Neurons in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Primate Model of Parkinson's Disease , 2002, The Journal of Neuroscience.

[147]  W. T. Thach Correlation of neural discharge with pattern and force of muscular activity, joint position, and direction of intended next movement in motor cortex and cerebellum. , 1978, Journal of neurophysiology.

[148]  Christof Koch,et al.  The Spiking Component of Oscillatory Extracellular Potentials in the Rat Hippocampus , 2012, The Journal of Neuroscience.

[149]  J. Bolam,et al.  Dopamine regulates the impact of the cerebral cortex on the subthalamic nucleus–globus pallidus network , 2001, Neuroscience.

[150]  A. Nieoullon,et al.  In a rat model of parkinsonism, lesions of the subthalamic nucleus reverse increases of reaction time but induce a dramatic premature responding deficit , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[151]  D. Perkel,et al.  Millisecond Timescale Disinhibition Mediates Fast Information Transmission through an Avian Basal Ganglia Loop , 2009, The Journal of Neuroscience.

[152]  Valeria C. Pazo,et al.  Electrophysiologic study of globus pallidus projections to the thalamic reticular nucleus , 2013, Brain Research Bulletin.

[153]  A P Georgopoulos,et al.  On the relations between the direction of two-dimensional arm movements and cell discharge in primate motor cortex , 1982, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[154]  Y. Shinoda,et al.  Synaptic organization of the cerebello-thalamo-cerebral pathway in the cat. II. Input-output organization of single thalamocortical neurons in the ventrolateral thalamus , 1985, Neuroscience Research.

[155]  M. Starr,et al.  Role of the ventromedial nucleus of the thalamus in motor behaviour—I. Effects of focal injections of drugs , 1983, Neuroscience.

[156]  D. Jaeger,et al.  Cortico-cerebellar coherence and causal connectivity during slow-wave activity , 2010, Neuroscience.

[157]  A. Nambu,et al.  Projection on the motor cortex of thalamic neurons with pallidal input in the monkey , 2004, Experimental Brain Research.

[158]  M. Bevan,et al.  Ionic Mechanisms Underlying Autonomous Action Potential Generation in the Somata and Dendrites of GABAergic Substantia Nigra Pars Reticulata Neurons In Vitro , 2005, The Journal of Neuroscience.

[159]  Robert S Turner,et al.  Context-Dependent Modulation of Movement-Related Discharge in the Primate Globus Pallidus , 2005, The Journal of Neuroscience.

[160]  J. Tepper,et al.  Cerebellar-responsive neurons in the thalamic ventroanterior-ventrolateral complex of rats: In vivo electrophysiology , 1994, Neuroscience.

[161]  Grigori N. Orlovsky,et al.  Activity of Different Classes of Neurons of the Motor Cortex during Postural Corrections , 2003, The Journal of Neuroscience.

[162]  H. Kwan,et al.  Statistical prediction of the optimal site for thalamotomy in parkinsonian tremor , 1995, Movement disorders : official journal of the Movement Disorder Society.

[163]  Matthew T. Kaufman,et al.  Neural population dynamics during reaching , 2012, Nature.

[164]  P. Ashby,et al.  Coherence between cerebellar thalamus, cortex and muscle in man: cerebellar thalamus interactions. , 2000, Brain : a journal of neurology.

[165]  A. Kraskov,et al.  The Activity of Primary Motor Cortex Corticospinal Neurons during Tool Use by Macaque Monkeys , 2012, The Journal of Neuroscience.

[166]  R. Llinás,et al.  Bursting of thalamic neurons and states of vigilance. , 2006, Journal of neurophysiology.

[167]  B. Kampa,et al.  Synaptic integration in dendritic trees. , 2005, Journal of neurobiology.

[168]  KouichiC . Nakamura,et al.  Temporal Coupling with Cortex Distinguishes Spontaneous Neuronal Activities in Identified Basal Ganglia-Recipient and Cerebellar-Recipient Zones of the Motor Thalamus , 2012, Cerebral cortex.

[169]  A. Priori,et al.  Dopamine‐dependent non‐linear correlation between subthalamic rhythms in Parkinson's disease , 2006, The Journal of physiology.

[170]  S. T. Sakai,et al.  Nigrothalamic projections and nigrothalamocortical pathway to the medial agranular cortex in the rat: Single‐ and double‐labeling light and electron microscopic studies , 1998, The Journal of comparative neurology.

[171]  P. Strick,et al.  Activity of ventrolateral thalamic neurons during arm movement. , 1976, Journal of neurophysiology.

[172]  A. Oliviero,et al.  Dopamine-dependent changes in the functional connectivity between basal ganglia and cerebral cortex in humans. , 2002, Brain : a journal of neurology.

[173]  J. Deniau,et al.  Inhibitory nigral influence on cerebellar evoked responses in the rat ventromedial thalamic nucleus , 2004, Experimental Brain Research.

[174]  S. Raeva,et al.  Analysis of evoked activity patterns of human thalamic ventrolateral neurons during verbally ordered voluntary movements , 1999, Neuroscience.

[175]  E. Trouche,et al.  Initiation of a goal-directed movement in the monkey , 1980, Experimental Brain Research.

[176]  M. Steriade,et al.  Control of unitary activities in cerebellothalamic pathway during wakefulness and synchronized sleep. , 1971, Journal of neurophysiology.

[177]  D. Xiao,et al.  Laminar and modular organization of prefrontal projections to multiple thalamic nuclei , 2009, Neuroscience.

[178]  B. Cohen,et al.  Intraoperative local field recording for deep brain stimulation in Parkinson's disease and essential tremor , 2010, Movement disorders : official journal of the Movement Disorder Society.

[179]  N. Franks General anaesthesia: from molecular targets to neuronal pathways of sleep and arousal , 2008, Nature Reviews Neuroscience.

[180]  Kuei Yuan Tseng,et al.  Cortical Slow Oscillatory Activity Is Reflected in the Membrane Potential and Spike Trains of Striatal Neurons in Rats with Chronic Nigrostriatal Lesions , 2001, The Journal of Neuroscience.

[181]  C. Colwell,et al.  Chronic Hyperosmotic Stress Converts GABAergic Inhibition into Excitation in Vasopressin and Oxytocin Neurons in the Rat , 2011, The Journal of Neuroscience.

[182]  S. Sherman The thalamus is more than just a relay , 2007, Current Opinion in Neurobiology.

[183]  A. Morel,et al.  Single-unit analysis of the pallidum, thalamus and subthalamic nucleus in parkinsonian patients , 2000, Neuroscience.

[184]  Paul B. Johnson,et al.  Making arm movements within different parts of space: dynamic aspects in the primate motor cortex , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[185]  G. Hu,et al.  Electrophysiological and morphological properties of pyramidal and nonpyramidal neurons in the cat motor cortex in vitro , 1996, Neuroscience.

[186]  H. Kita,et al.  Responses of rat substantia nigra pars reticulata units to cortical stimulation , 1992, Neuroscience Letters.

[187]  J. Dostrovsky,et al.  Beta oscillatory activity in the subthalamic nucleus and its relation to dopaminergic response in Parkinson's disease. , 2006, Journal of neurophysiology.

[188]  P. Brown,et al.  New insights into the relationship between dopamine, beta oscillations and motor function , 2011, Trends in Neurosciences.

[189]  H. Kwan,et al.  Single unit analysis of the human ventral thalamic nuclear group. Tremor-related activity in functionally identified cells. , 1994, Brain : a journal of neurology.

[190]  C. I. Connolly,et al.  Building neural representations of habits. , 1999, Science.

[191]  Hagai Bergman,et al.  Comparison of MPTP-induced changes in spontaneous neuronal discharge in the internal pallidal segment and in the substantia nigra pars reticulata in primates , 1999, Experimental Brain Research.

[192]  D. Guehl,et al.  Neuronal activity in the monkey motor thalamus during bicuculline‐induced dystonia , 2002, The European journal of neuroscience.

[193]  Andrea A. Kühn,et al.  Pathological synchronisation in the subthalamic nucleus of patients with Parkinson's disease relates to both bradykinesia and rigidity , 2009, Experimental Neurology.

[194]  A. P. Georgopoulos,et al.  Neuronal population coding of movement direction. , 1986, Science.

[195]  A. Ueki The mode of nigro-thalamic transmission investigated with intracellular recording in the cat , 2004, Experimental Brain Research.

[196]  D. A. Bergstrom,et al.  Phase relationships support a role for coordinated activity in the indirect pathway in organizing slow oscillations in basal ganglia output after loss of dopamine , 2007, Neuroscience.

[197]  S. Haber,et al.  The cortico-basal ganglia integrative network: The role of the thalamus , 2009, Brain Research Bulletin.

[198]  H. Asanuma,et al.  Importance of the projection from the sensory to the motor cortex for recovery of motor function following partial thalamic lesion in the monkey , 1987, Brain Research.

[199]  Graeme Eisenhofer,et al.  Dopamine lesion‐induced changes in subthalamic nucleus activity are not associated with alterations in firing rate or pattern in layer V neurons of the anterior cingulate cortex in anesthetized rats , 2007, The European journal of neuroscience.

[200]  J. Dostrovsky,et al.  High-frequency Synchronization of Neuronal Activity in the Subthalamic Nucleus of Parkinsonian Patients with Limb Tremor , 2000, The Journal of Neuroscience.

[201]  D. Jacobowitz,et al.  Distribution of calretinin, calbindin-D28k, and parvalbumin in the rat thalamus , 1994, Brain Research Bulletin.

[202]  William M. Connelly,et al.  Temporally Selective Firing of Cortical and Thalamic Neurons during Sleep and Wakefulness , 2012, The Journal of Neuroscience.

[203]  J. Murphy,et al.  Activities of neurons in "motor" thalamus during control of limb movement in the primate. , 1980, Journal of Neurophysiology.

[204]  M. Sirota,et al.  Three Channels of Corticothalamic Communication during Locomotion , 2005, The Journal of Neuroscience.

[205]  J. Deniau,et al.  Subthalamic nucleus high‐frequency stimulation generates a concomitant synaptic excitation–inhibition in substantia nigra pars reticulata , 2011, The Journal of physiology.

[206]  M. E. Anderson,et al.  Changes in the control of arm position, movement, and thalamic discharge during local inactivation in the globus pallidus of the monkey. , 1996, Journal of neurophysiology.

[207]  C. McIntyre,et al.  Thalamocortical relay fidelity varies across subthalamic nucleus deep brain stimulation protocols in a data-driven computational model. , 2008, Journal of neurophysiology.

[208]  G. E. Alexander,et al.  Functional architecture of basal ganglia circuits: neural substrates of parallel processing , 1990, Trends in Neurosciences.

[209]  T. Klockgether,et al.  Behavioral actions of baclofen in the rat ventromedial thalamic nucleus: antagonism by δ-aminovalerate , 1987, Brain Research.

[210]  M. Hallett,et al.  Cerebral causes and consequences of parkinsonian resting tremor: a tale of two circuits? , 2012, Brain : a journal of neurology.

[211]  R. Faull,et al.  The distribution and morphology of identified thalamocortical projection neurons and glial cells with reference to the question of interneurons in the ventrolateral nucleus of the rat thalamus , 1987, Neuroscience.

[212]  J. Deniau,et al.  Disinhibition as a basic process in the expression of striatal functions. II. The striato-nigral influence on thalamocortical cells of the ventromedial thalamic nucleus , 1985, Brain Research.

[213]  E. Kuramoto,et al.  Complementary distribution of glutamatergic cerebellar and GABAergic basal ganglia afferents to the rat motor thalamic nuclei , 2011, The European journal of neuroscience.

[214]  P. Strick,et al.  Multiple output channels in the basal ganglia. , 1993, Science.

[215]  I. Grofová,et al.  Cerebellar projections to the nuclei ventralis lateralis and ventralis anterior thalami , 2004, Brain Structure and Function.

[216]  Iwona Stepniewska,et al.  Pallidal and cerebellar afferents to pre‐supplementary motor area thalamocortical neurons in the owl monkey: A multiple labeling study , 2000, The Journal of comparative neurology.

[217]  E. Welker,et al.  Dual morphology and topography of the corticothalamic terminals originating from the primary, supplementary motor, and dorsal premotor cortical areas in Macaque monkeys , 1998, The Journal of comparative neurology.

[218]  Alison L. Barth,et al.  Experimental evidence for sparse firing in the neocortex , 2012, Trends in Neurosciences.

[219]  A. Schmied,et al.  Activity of ventrolateral thalamic neurons in relation to a simple reaction time task in the cat , 1979, Experimental Brain Research.

[220]  J. Velíšková,et al.  Topographical connections of the substantia nigra pars reticulata to higher-order thalamic nuclei in the rat , 2012, Brain Research Bulletin.

[221]  R. Sieb Proposed mechanisms for cerebellar coordination, stabilization and monitoring of movements and posture. , 1989, Medical hypotheses.

[222]  H. Bergman,et al.  The primate subthalamic nucleus. II. Neuronal activity in the MPTP model of parkinsonism. , 1994, Journal of neurophysiology.

[223]  I. Raman,et al.  Resurgent Sodium Current and Action Potential Formation in Dissociated Cerebellar Purkinje Neurons , 1997, The Journal of Neuroscience.

[224]  R. Llinás,et al.  Central motor loop oscillations in parkinsonian resting tremor revealed magnetoencephalography , 1996, Neurology.

[225]  Hiroyuki Kitano,et al.  Substantia nigra output to prefrontal cortex via thalamus in monkeys. II. Activity of thalamic relay neurons in delayed conditional go/no-go discrimination task. , 2009, Journal of neurophysiology.

[226]  Michale S Fee,et al.  Vocal babbling in songbirds requires the basal ganglia-recipient motor thalamus but not the basal ganglia. , 2011, Journal of neurophysiology.

[227]  N. Wetzel SURGICAL TREATMENT OF PARKINSON'S DISEASE. , 1963, Chicago medicine.

[228]  Michael S Okun,et al.  Lesion therapy for Parkinson's disease and other movement disorders: Update and controversies , 2004, Movement disorders : official journal of the Movement Disorder Society.

[229]  Y. Kawaguchi,et al.  Differentiated Participation of Thalamocortical Subnetworks in Slow/Spindle Waves and Desynchronization , 2012, The Journal of Neuroscience.

[230]  R. Passingham,et al.  Motor learning in monkeys (Macaca fascicularis) with lesions in motor thalamus , 2004, Experimental Brain Research.

[231]  M. Uno,et al.  Monosynaptic inhibition of thalamic neurons produced by stimulation of the substantia nigra , 1977, Experientia.

[232]  Tetsuro Yamamoto,et al.  Electrophysiological and morphological studies on thalamic neurons receiving entopedunculo- and cerebello-thalamic projections in the cat , 1984, Brain Research.

[233]  J. Alonso,et al.  Thalamic Burst Mode and Inattention in the Awake LGNd , 2006, Neuron.

[234]  M. Starr,et al.  Role of the ventromedial nucleus of the thalamus in motor behaviour—II. Effects of lesions , 1983, Neuroscience.

[235]  Jean-Michel Deniau,et al.  Activity of Ventral Medial Thalamic Neurons during Absence Seizures and Modulation of Cortical Paroxysms by the Nigrothalamic Pathway , 2007, The Journal of Neuroscience.

[236]  Nikolaus R. McFarland,et al.  Thalamic Relay Nuclei of the Basal Ganglia Form Both Reciprocal and Nonreciprocal Cortical Connections, Linking Multiple Frontal Cortical Areas , 2002, The Journal of Neuroscience.

[237]  M. Mirmiran,et al.  Ambulatory monitoring of tremor and other movements before and after thalamotomy: A new quantitative technique , 1993, Journal of the Neurological Sciences.

[238]  Dieter Jaeger,et al.  Neuronal activity in the striatum and pallidum of primates related to the execution of externally cued reaching movements , 1995, Brain Research.

[239]  E. G. Jones,et al.  A new parcellation of the human thalamus on the basis of histochemical staining , 1989, Brain Research Reviews.

[240]  Hiroyuki Kitano,et al.  Substantia nigra output to prefrontal cortex via thalamus in monkeys. I. Electrophysiological identification of thalamic relay neurons. , 2009, Journal of neurophysiology.

[241]  M. Desmurget,et al.  Basal ganglia contributions to motor control: a vigorous tutor , 2010, Current Opinion in Neurobiology.

[242]  O. Hassani,et al.  Increased subthalamic neuronal activity after nigral dopaminergic lesion independent of disinhibition via the globus pallidus , 1996, Neuroscience.

[243]  T. Sawaguchi,et al.  GABAergic inhibition of neuronal activity in the primate motor and premotor cortex during voluntary movement. , 1992, Journal of neurophysiology.

[244]  D. Storm,et al.  The role of calmodulin as a signal integrator for synaptic plasticity , 2005, Nature Reviews Neuroscience.

[245]  M. Delong,et al.  Primate models of movement disorders of basal ganglia origin , 1990, Trends in Neurosciences.

[246]  J. Deniau,et al.  Basal ganglia and processing of cortical information: functional interactions between trans-striatal and trans-subthalamic circuits in the substantia nigra pars reticulata , 2003, Neuroscience.

[247]  L. Tremblay,et al.  Tremor‐related activity of neurons in the ‘motor’ thalamus: changes in firing rate and pattern in the MPTP vervet model of parkinsonism , 2003, The European journal of neuroscience.

[248]  B Hyland,et al.  Cortical cell assemblies: a possible mechanism for motor programs. , 1994, Journal of motor behavior.

[249]  Abbas F. Sadikot,et al.  The impact of ventrolateral thalamotomy on tremor and voluntary motor behavior in patients with Parkinson’s disease , 2006, Experimental Brain Research.

[250]  D. McCormick,et al.  Simulation of the currents involved in rhythmic oscillations in thalamic relay neurons. , 1992, Journal of neurophysiology.

[251]  J. Kalaska,et al.  A comparison of movement direction-related versus load direction- related activity in primate motor cortex, using a two-dimensional reaching task , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[252]  Gilles Bertrand,et al.  Optimal location of thalamotomy lesions for tremor associated with Parkinson disease: a probabilistic analysis based on postoperative magnetic resonance imaging and an integrated digital atlas. , 2002, Journal of neurosurgery.

[253]  J. Deniau,et al.  Effect of substantia nigra stimulation on identified neurons in the VL-VA thalamic complex: Comparison between intact and chronically decorticated cats , 1978, Brain Research.

[254]  J. Dostrovsky,et al.  Neuronal Oscillations in the Basal Ganglia and Movement Disorders: Evidence from Whole Animal and Human Recordings , 2004, The Journal of Neuroscience.

[255]  Thomas Boraud,et al.  Dynamic changes in the cortex-basal ganglia network after dopamine depletion in the rat. , 2008, Journal of neurophysiology.

[256]  P. Dean,et al.  The cerebellar microcircuit as an adaptive filter: experimental and computational evidence , 2010, Nature Reviews Neuroscience.

[257]  P. Strick,et al.  Supplementary Motor Area and Presupplementary Motor Area: Targets of Basal Ganglia and Cerebellar Output , 2007, The Journal of Neuroscience.

[258]  I. Ilinsky,et al.  Fine structure of the ventral lateral nucleus (VL) of the Macaca mulatta thalamus: Cell types and synaptology , 1991, The Journal of comparative neurology.

[259]  A. Aertsen,et al.  Dynamics of neuronal interactions in monkey cortex in relation to behavioural events , 1995, Nature.

[260]  S. Sherman Tonic and burst firing: dual modes of thalamocortical relay , 2001, Trends in Neurosciences.

[261]  Louise C. Parr-Brownlie,et al.  Beta frequency synchronization in basal ganglia output during rest and walk in a hemiparkinsonian rat , 2010, Experimental Neurology.

[262]  I. Grofová,et al.  Cortical and pallidal projections to the nucleus ventralis lateralis thalami , 2004, Anatomy and Embryology.

[263]  J. Deniau,et al.  Relationships between the Prefrontal Cortex and the Basal Ganglia in the Rat: Physiology of the Cortico-Nigral Circuits , 1999, The Journal of Neuroscience.

[264]  A. Parent,et al.  Projections of cholinergic and non-cholinergic neurons of the brainstem core to relay and associational thalamic nuclei in the cat and macaque monkey , 1988, Neuroscience.

[265]  J. Murphy,et al.  Single unit analysis of the human ventral thalamic nuclear group: correlation of thalamic "tremor cells" with the 3-6 Hz component of parkinsonian tremor , 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[266]  Andrea A. Kühn,et al.  Gamma oscillations in the human basal ganglia , 2013, Experimental Neurology.

[267]  Hideki Oshima,et al.  Difference in surgical strategies between thalamotomy and thalamic deep brain stimulation for tremor control , 2005, Journal of Neurology.

[268]  J. Lisman Bursts as a unit of neural information: making unreliable synapses reliable , 1997, Trends in Neurosciences.

[269]  G. Percheron,et al.  The primate motor thalamus , 1996, Brain Research Reviews.

[270]  T. Sawaguchi,et al.  Depth distribution of neuronal activity related to a visual reaction time task in the monkey prefrontal cortex. , 1989, Journal of neurophysiology.

[271]  E. Vaadia,et al.  Spike Synchronization in the Cortex-Basal Ganglia Networks of Parkinsonian Primates Reflects Global Dynamics of the Local Field Potentials , 2004, The Journal of Neuroscience.

[272]  Driss Boussaoud,et al.  Origin of thalamic inputs to the primary, premotor, and supplementary motor cortical areas and to area 46 in macaque monkeys: A multiple retrograde tracing study , 1999, The Journal of comparative neurology.

[273]  O. Lindvall,et al.  The adrenergic innervation of the rat thalamus as revealed by the glyoxylic acid fluorescence method , 1974, The Journal of comparative neurology.

[274]  J. Dostrovsky,et al.  Tremor cells in the human thalamus: differences among neurological disorders. , 2004, Journal of neurosurgery.

[275]  Yosef Yarom,et al.  A model of the olivo-cerebellar system as a temporal pattern generator , 2008, Trends in Neurosciences.

[276]  S. D. Meriney,et al.  Are unreliable release mechanisms conserved from NMJ to CNS? , 2013, Trends in Neurosciences.

[277]  V. Braitenberg,et al.  The detection and generation of sequences as a key to cerebellar function: Experiments and theory , 1997, Behavioral and Brain Sciences.

[278]  Y. Lamarre,et al.  Single cell activity in the ventral lateral thalamus of the unanesthetized monkey. , 1974, Experimental neurology.

[279]  J. Hirsch,et al.  Sleep-related variations of membrane potential in the lateral geniculate body relay neurons of the cat , 1983, Brain Research.