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

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          Abstract

          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.

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          Short-term synaptic plasticity.

          Synaptic transmission is a dynamic process. Postsynaptic responses wax and wane as presynaptic activity evolves. This prominent characteristic of chemical synaptic transmission is a crucial determinant of the response properties of synapses and, in turn, of the stimulus properties selected by neural networks and of the patterns of activity generated by those networks. This review focuses on synaptic changes that result from prior activity in the synapse under study, and is restricted to short-term effects that last for at most a few minutes. Forms of synaptic enhancement, such as facilitation, augmentation, and post-tetanic potentiation, are usually attributed to effects of a residual elevation in presynaptic [Ca(2+)]i, acting on one or more molecular targets that appear to be distinct from the secretory trigger responsible for fast exocytosis and phasic release of transmitter to single action potentials. We discuss the evidence for this hypothesis, and the origins of the different kinetic phases of synaptic enhancement, as well as the interpretation of statistical changes in transmitter release and roles played by other factors such as alterations in presynaptic Ca(2+) influx or postsynaptic levels of [Ca(2+)]i. Synaptic depression dominates enhancement at many synapses. Depression is usually attributed to depletion of some pool of readily releasable vesicles, and various forms of the depletion model are discussed. Depression can also arise from feedback activation of presynaptic receptors and from postsynaptic processes such as receptor desensitization. In addition, glial-neuronal interactions can contribute to short-term synaptic plasticity. Finally, we summarize the recent literature on putative molecular players in synaptic plasticity and the effects of genetic manipulations and other modulatory influences.
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            Neural population dynamics during reaching

            Most theories of motor cortex have assumed that neural activity represents movement parameters. This view derives from an analogous approach to primary visual cortex, where neural activity represents patterns of light. Yet it is unclear how well that analogy holds. Single-neuron responses in motor cortex appear strikingly complex, and there is marked disagreement regarding which movement parameters are represented. A better analogy might be with other motor systems, where a common principle is rhythmic neural activity. We found that motor cortex responses during reaching contain a brief but strong oscillatory component, something quite unexpected for a non-periodic behavior. Oscillation amplitude and phase followed naturally from the preparatory state, suggesting a mechanistic role for preparatory neural activity. These results demonstrate unexpected yet surprisingly simple structure in the population response. That underlying structure explains many of the confusing features of individual-neuron responses.
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              General anaesthesia: from molecular targets to neuronal pathways of sleep and arousal.

              The mechanisms through which general anaesthetics, an extremely diverse group of drugs, cause reversible loss of consciousness have been a long-standing mystery. Gradually, a relatively small number of important molecular targets have emerged, and how these drugs act at the molecular level is becoming clearer. Finding the link between these molecular studies and anaesthetic-induced loss of consciousness presents an enormous challenge, but comparisons with the features of natural sleep are helping us to understand how these drugs work and the neuronal pathways that they affect. Recent work suggests that the thalamus and the neuronal networks that regulate its activity are the key to understanding how anaesthetics cause loss of consciousness.
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                Author and article information

                Journal
                Front Comput Neurosci
                Front Comput Neurosci
                Front. Comput. Neurosci.
                Frontiers in Computational Neuroscience
                Frontiers Media S.A.
                1662-5188
                11 November 2013
                2013
                : 7
                : 163
                Affiliations
                [1]1Department of Anatomy, Otago School of Medical Science, University of Otago Dunedin, New Zealand
                [2]2Brain Health Research Centre, Otago School of Medical Science, University of Otago Dunedin, New Zealand
                [3]3Department of Physiology, Otago School of Medical Science, University of Otago Dunedin, New Zealand
                Author notes

                Edited by: Hagai Bergman, The Hebrew University of Jerusalem, Israel

                Reviewed by: Robert S. Turner, University of Pittsburgh, USA; Rea Mitelman, The Hebrew University of Jerusalem, Israel; Jesse Goldberg, Cornell University, USA

                *Correspondence: Louise C. Parr-Brownlie, Department of Anatomy, University of Otago, Lindo Ferguson Building, PO Box 913, 270 Great King Street, Dunedin 9054, New Zealand e-mail: louise.parr-brownlie@ 123456otago.ac.nz

                This article was submitted to the journal Frontiers in Computational Neuroscience.

                Article
                10.3389/fncom.2013.00163
                3822295
                24273509
                3bde50d6-70b8-400b-940b-3861446c3b7b
                Copyright © 2013 Bosch-Bouju, Hyland and Parr-Brownlie.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 30 July 2013
                : 24 October 2013
                Page count
                Figures: 4, Tables: 0, Equations: 0, References: 278, Pages: 21, Words: 21317
                Categories
                Neuroscience
                Review Article

                Neurosciences
                motor thalamus,basal ganglia,motor cortex,cerebellum,parkinson’s disease,lts burst
                Neurosciences
                motor thalamus, basal ganglia, motor cortex, cerebellum, parkinson’s disease, lts burst

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