Motor Learning and Synaptic Plasticity: BBS Call for Commentators

Below are the abstracts for 8 forthcoming target articles on MOTOR LEARNING AND SYNAPTIC PLASTICITY to appear in BBS's Special Issue: Controversies in Neurosciences IV [commentators may comment on one, several, or all 8 target articles] (1) bbs.crepel: CELLULAR MECHANISMS OF LONG-TERM DEPRESSION IN THE CEREBELLUM (2) bbs.houk: MODELS OF THE CEREBELLUM AND MOTOR LEARNING (3) bbs.kano: POTENTIATION OF GABAERGIC INHIBITORY TRANSMISSION PURKINJE CELLS (4) bbs.linden: CEREBELLAR LONG-TERM DEPRESSION IN CELL CULTURE (5) bbs.simpson: ON CLIMBING FIBER SIGNALS AND THEIR CONSEQUENCE(S) (6) bbs.smith: CEREBELLAR LEARNING AND OPTIMAL JOINT STIFFNESS CONTROL (7) bbs.hach: CEREBELLUM, MOTOR LEARNING AND THINKING IN MAN: PET STUDIES (8) bbs.vincent: NITRIC OXIDE AND SYNAPTIC PLASTICITY: NO NEWS FROM CEREBELLUM These 8 articles have been accepted for co-publication in Behavioral and Brain Sciences (BBS), an international, interdisciplinary journal providing Open Peer Commentary on important and controversial current research in the biobehavioral and cognitive sciences. Commentators must be current BBS Associates or nominated by a current BBS Associate. To be considered as a commentator for this article, to suggest other appropriate commentators, or for information about how to become a BBS Associate, please send email to: bbs(a)ecs.soton.ac.uk or write to: Behavioral and Brain Sciences Department of Psychology University of Southampton Highfield, Southampton SO17 1BJ UNITED KINGDOM http://cogsci.ecs.soton.ac.uk/~harnad/bbs.html gopher://gopher.princeton.edu:70/11/.libraries/.pujournals ftp://ftp.princeton.edu/pub/harnad/BBS To help us put together a balanced list of commentators, please give some indication of the aspects of the topic on which you would bring your areas of expertise to bear if you were selected as a commentator. Electronic draft of the full texts of all 8 are available for inspection by anonymous ftp (or gopher or [best method] WorldWide Web) according to the instructions that follow after the 8 abstracts. Commentators may comment on one, several, or all 8 target articles. Commentary length is 1000 words for a commentary on one target article, to a maximum of 2000 words for a commentary on all 8 (i.e. about 140 additional words for each additional target article). (1) CELLULAR MECHANISMS OF LONG-TERM DEPRESSION IN THE CEREBELLUM F. Crepel, N. Hemart, D. Jaillard and H. Daniel Laboratoire de Neurobiologie et Neuropharmacologie du Dveloppement, CNRS URA 1121, Bat. 440, Universit Paris-Sud, 91405 Orsay, France FILENAME: bbs.neur4.crepel KEYWORDS: rat, slice, synaptic-plasticity, cerebellum, excitatory amino-acid receptors, protein kinases, nitric oxide, cGMP, desensitization. ABSTRACT: Summary Long-term depression (LTD) of synaptic transmission at parallel fibre-Purkinje cell synapses is thought to be a cellular substrate of motor learning in the cerebellum. This use-dependent change in synaptic efficacy is induced by conjunctive stimulation of parallel fibres and climbing fibres. Researchers agree that the induction of LTD requires, as a initial step, a calcium influx via voltage-gated Ca 2+ channels into Purkinje cell, together with activation of ionotropic (AMPA) and probably metabotropic subtypes of glutamate receptors of this cell. Indeed, due to the lack of specific antagonist, the final demonstration of the contribution of metabotropic receptors in the LTD induction process, under founctional conditions, remains unanswered. The debate is now focused on the second-messenger processes leading to LTD of synaptic transmission at parallel fibre-Purkinje cell synapses, after the calcium influx into the cell. All researchers agree that a calcium-dependent cascade of events, including activation of protein kinase C, is necessary for LTD induction. However, the recruitment in the LTD induction, of another cascade also triggered by Ca 2+ through synthesis of nitric oxide and cyclic GMP, remains controversial. On the other hand, growing evidences suggest that these chains of reaction underlying LTD migh ultimately lead to a genuine change in the functional characteristics of AMPA recepotors at the parallel fibre-Purkinje cell synapses. ============================================================================ (2) MODELS OF THE CEREBELLUM AND MOTOR LEARNING James C. Houk, Jay T. Buckingham and Andrew G. Barto Department of Physiology Northwestern University Medical School Chicago, Illinois 60611 houk(a)casbah.acns.nwu.edu Department of Computer Science University of Massachusetts Amherst, Massachusetts 01003 buckingham(a)cs.umass.edu Barto(a)cs.umass.edu FILENAME: bbs.neur4.houk ABSTRACT: This article reviews models of the cerebellum and motor learning starting with the landmark papers by Marr and Albus and going through present times. The unique architecture of the cerebellar cortex is ideally suited for pattern recognition, but how is pattern recognition incorporated into motor control and learning systems? The present analysis begins with a discussion of what the cerebellar cortex needs to regulate through its anatomically defined projections to premotor networks. Next we examine various models of how the microcircuitry in the cerebellar cortex may be used to achieve its regulatory functions. Having thus defined what it is that Purkinje cells in the cerebellar cortex must learn, we then evaluate theories of motor learning. We examine current models of synaptic plasticity, credit assignment and the generation of training information, indicating how they could function cooperatively to guide the processes of motor learning. ============================================================================ (3) LONG-LASTING POTENTIATION OF GABAERGIC INHIBITORY SYNAPTIC TRANSMISSION IN CEREBELLAR PURKINJE CELLS: ITS PROPERTIES AND POSSIBLE MECHANISMS Masanobu Kano Department of Physiology Jichi Medical School Minamikawachi-machi Tochigi 329-04, Japan H00851(a)sinet.ad.jp FILENAME: bbs.neur4.kano KEYWORDS: cerebellum, Purkinje cell, inhibitory synapse, GABAA receptor, long-lasting potentiation, Ca2+, protein kinase ABSTRACT: The cellular basis of motor learning in the cerebellum has been attributed mostly to long-term depression (LTD) at excitatory parallel fiber (PF)-Purkinje cell (PC) synapses. LTD is induced when PFs are activated in conjunction with a climbing fiber (CF), the other excitatory input to PCs. Recently, by using whole- cell patch-clamp recording from PCs in cerebellar slices, a new form of synaptic plasticity was discovered. Stimulation of excitatory CFs induced a long-lasting (usually longer than 30 min) 'rebound potentiation (RP)' of g-amino-butyric acid A (GABAA)-receptor mediated inhibitory postsynaptic currents (IPSCs). Similar to LTD, induction of RP requires transient elevation of intracellular calcium concentration ([Ca2+]i) due to activation of voltage-gated Ca2+ channels. Besides, activity of inhibitory synapses seems to be necessary for RP to occur. RP is mainly due to up-regulation of postsynaptic GABAA receptor function, since PC response to bath-applied exogenous GABA is also potentiated with a time course similar to RP. The difference in the time scale between the Ca2+ transients (10-30 sec) and the durations of RP (>30 min) strongly suggests that some intracellular biochemical machinery is involved. Besides the well-described LTD, RP could be a cellular mechanism that plays an important role in motor learning. ============================================================================ (4) CEREBELLAR LONG-TERM DEPRESSION AS INVESTIGATED IN A CELL CULTURE PREPARATION David J. Linden Department of Neuroscience Johns Hopkins University School of Medicine 725 North Wolfe Street Baltimore, MD 21205, USA david.linden(a)qmail.bs.jhu.edu FILENAME: bbs.neur4.linden KEYWORDS: Purkinje Neuron, Glutamate, Motor Learning, Synaptic Plasticity, Climbing Fiber, Parallel Fiber. ABSTRACT: Cerebellar long-term depression (LTD) is a form of synaptic plasticity, first described by Ito and co-workers, in which simultaneous activation of two excitatory inputs to a Purkinje neuron, the parallel fibers (PF) and the climbing fibers (CF), results in a sustained depression of PF synaptic drive. The purpose of this target article is not to assess the possible role of this synaptic alteration in motor learning, an issue which is addressed by other authors in this volume, nor is it to provide a detailed summary of the work on cerebellar LTD to this point (see Linden and Connor, 1993; Crepel et al., 1993 for review) or to place cerebellar LTD within the context of other forms of persistent synaptic depression that occur within the mammalian brain (see Linden, 1994b). Rather, it is to discuss results obtained using a very reduced preparation for the study of LTD, embryonic Purkinje neurons grown in culture and stimulated with exogenous excitatory amino acids, and to consider some advantages and limitations of this approach. Recent work using this preparation has suggested that three processes are necessary for the induction of cerebellar LTD, Ca influx through voltage-gated channels, Na influx through AMPA receptor-associated channels or voltage- gated Na channels, and protein kinase C activation which is dependent upon activation of the metabotropic glutamate receptor mGLUR1. In addition, input-specific induction of LTD has been demonstrated in this preparation under conditions where both spontaneous and evoked neurotransmitter release are reduced or eliminated, indicating that postsynaptic alterations are sufficient to confer this important computational property. ============================================================================ (5) ON CLIMBING FIBER SIGNALS AND THEIR CONSEQUENCE(S) J.I. Simpson, D.R. Wylie, and C.I. De Zeeuw Dept. of Physiology and Neuroscience New York University Medical Center 550 First Avenue New York, NY 10016 simpsj01(a)popmail.med.nyu.edu Dept. of Psychology, University of Alberta, Edmonton, Alberta, Canada, T6G 2E1. Dept. of Anatomy, Erasmus University Rotterdam, 3000 DR Rotterdam, Postbus 1738, The Netherlands. FILENAME: bbs.neur4.simpson KEYWORDS: cerebellum, Purkinje cells, mossy fibers, synchrony, complex spikes, simple spikes, movement, posture, inferior olive, eye movements, flocculus, nodulus ABSTRACT: The persistence of many contrasting notions of climbing fiber function after years of investigation testifies that the issue of climbing fiber contributions to cerebellar transactions is still unresolved. The proposed capabilities of the climbing fibers cover an impressive spectrum. For many researchers, the climbing fibers signal errors in motor performance, either in the conventional manner of frequency modulation or as a single announcement of an "unexpected event". More controversial is the effect of these signals on the simple spike modulation of Purkinje cells. In some hands, they lead to a long-term depression of the strength of parallel fiber synapses, while in other hands they lead to a short-lasting enhancement of the responsiveness of Purkinje cells to mossy fiber inputs, or contribute to the often seen reciprocal relation between complex and simple spike modulation. For yet other investigators, the climbing fibers serve internal timing functions through their capacity for synchronous and rhythmic firing. The above viewpoints are presented in the spirit of trying to reach some consensus about climbing fiber function. Each point of view is introduced by summarizing the key observations made by the respective proponents and then the issues of short-lasting enhancement, reciprocity between complex and simple spikes, and synchrony and rhythmicity are addressed in the context of the visual climbing fiber system of the vestibulocerebellum. ============================================================================ (6) DOES THE CEREBELLUM LEARN STRATEGIES FOR THE OPTIMAL TIME-VARYING CONTROL OF JOINT STIFFNESS? Allan M. Smith Centre de recherche en sciences neurologiques Departement de physiologie Universite de Montreal C.P. 6128, Succ. A Montreal (Quebec) H3C 3J7 smitha(a)ere.umontreal.ca FILENAME: bbs.neur4.smith KEYWORDS: muscle synergies, agonist-antagonist co-contraction, joint stiffness, muscle activation strategies, multjoint limb control, cerebellum, motor learning ABSTRACT: Although there is increasing agreement that the cerebellum plays an important role in motor learning, the basic substance of what constitutes motor learning has been difficult to define. Unless motor learning is somehow radically different from other forms of learning, it must involve relatively simple stimulus-stimulus and stimulus-response associations. All forms of learning, including purely sensory associations and cognitive learning as well as motor learning effect changes in behavior generally. However, a singular characteristic of motor learning is that it adjusts joint and limb mechanics by altering the neural input to muscles through practice and mental rehearsal. The hypothesis proposed here is that the cerebellum plays an important role in motor learning by forming and storing associated muscle activation patterns for the time-varying control of limb mechanics. By modulating the co-contraction of agonist-antagonist muscles through adjustments in the timing and amplitude of muscle activity, the viscoelastic properties of joints can be appropriately regulated throughout movement and adapted for transitions between postures and movements. Optimal control of joint viscoelastic properties cannot be totally achieved by on-line corrections initiated by reflex feedback, because of the delays and consequent instabilities incurred. Instead, strategies for optimizing muscle activation patterns or synergies must be learned from the temporal association of proprioceptive stimuli signaling muscle lengths and forces and the rates of changes in these parameters with the reinforcement occurring when the movement achieves its objective. Such strategies would involve varying degrees of co-contraction or reciprocal inhibition of agonist-antagonist muscles which ultimately contribute to the joint and limb stiffness. Evidence from neural recordings and clinical and experimental lesion studies are presented suggesting that the cerebellum uses teleceptive and proprioceptive feedback as feedforward conditioned stimuli for specific muscle activation patterns contributing to joint stiffness (i.e. agonist-antagonist muscle synergies) for particular tasks and postures. A wide variety of observations are thought to be consistent with such a role for the cerebellum, but ultimately additional experiments could prove or disprove this hypothesis. ============================================================================ (7) ON THE SPECIFIC ROLE OF THE CEREBELLUM IN MOTOR LEARNING AND COGNITION: CLUES FROM PET ACTIVATION AND LESION STUDIES IN MAN W. T. Thach Department of Anatomy and Neurobiology Washington University School of Medicine 660 South Euclid Avenue St. Louis, MO 63110 thachw(a)thalamus.wustl.edu FILENAME: bbs.neur4.thach KEYWORDS: cerebellum, motor learning, mental movement imagery, planning, sequence, timing, cognition. ABSTRACT: Brindley proposed that we initially generate movements "consciously", under higher cerebral control. As the movement is practiced, the cerebellum learns to link within itself the context in which the movement is made to the lower level movement generators. Marr and Albus proposed that the linkage is established by a special input from the inferior olive which plays upon an input-output element within the cerebellum during the period of the learning. When the linkage is complete, the occurrence of the context (represented by a certain input to the cerebellum) will trigger (through the cerebellum) the appropriate motor response. The "learned" movement is distinguished from the "unlearned" conscious movement by its now being automatic, rapid, and stereotyped. The idea is still controversial, but has been supported by a variety of animal studies and, as reviewed here, is consistent with the results of a number of human PET and ablation studies. We add to the idea of context-response linkage what we think is another important variable: novel combinations of downstream elements. With regard to the motor system and the muscles, this could explain how varied combinations of muscles may become active in precise time-amplitude specifications so as to produce coordinated movements appropriate to specific contexts. In this article we further extend this idea to the premotor parts of the brain, and their role in cognition. These areas receive influences from the cerebellum, are active both in planning movements that are to be executed, and in thinking about movements that are not to be executed. From recent evidence, the cerebellar output extends even to what has been characterized as the ultimate frontal planning area, the "prefrontal" cortex, area 46. The cerebellum thus may be involved in context-response linkage, and response combination even at these higher levels. The implication would be that, through practice, an experiential context would automatically evoke a certain mental action plan. The plan would be in the realm of thought, and either could--or need not--lead to execution. The specific cerebellar contribution would be one of the context linkage and the shaping of the response, through trial and error learning. The prefrontal and premotor areas could still plan without the help of the cerebellum, but not so automatically, rapidly, stereotypically, so precisely linked to context, or so free of error. Nor would their activities improve optimally with mental practice. ============================================================================ (8) NITRIC OXIDE AND SYNAPTIC PLASTICITY; NO NEWS FROM THE CEREBELLUM Steven R. Vincent Division of Neurological Sciences Department of Psychiatry University of British Columbia 2255 Wesbrook Mall Vancouver, B.C. V6T 1Z3 Canada steven.r.vincent(a)mtsg.ubc.ca FILENAME: bbs.neur4.vincent KEYWORDS: Nitric oxide, cyclic guanosine monophosphate (cGMP), cerebellar cortex, synaptic plasticity, guanylyl cyclase ABSTRACT: Interest in the role of nitric oxide (NO) in the nervous system began with the demonstration that glutamate receptor activation in cerebellar slices causes the formation of a diffusible messenger with properties similar to those of the endothelial derived relaxing factor. It is now clear that this is due to the Ca2+/calmodulin-dependent activation of the enzyme NO synthase, which forms NO and citrulline from the amino acid L-arginine. The cerebellum has very high levels of NO synthase, and although it has low levels of guanylyl cyclase, cerebellar cGMP levels are an order of magnitude higher than in other brain regions. A transcellular metabolic pathway is also present in the cerebellar cortex to recycle citrulline back to arginine. The NO formed binds to and activates soluble guanylyl cyclase to elevate cGMP levels in target cells. Studies employing NADPH-diaphorase, a selective histochemical marker for NO synthase, together with immunohistochemistry, in situ hybridization and biochemical studies have indicated that NO production occurs in granule and basket cells in the cerebellar cortex, while cGMP formation appears to occur largely in other cells, including Purkinje cells. Given that a long-term depression of AMPA currents can be seen in isolated Purkinje cells, this anatomical localization suggests that NO cannot play an essential role in the induction of this form of synaptic plasticity. ============================================================================ ============================================================================ To help you decide whether you would be an appropriate commentator for these articles, electronic drafts are retrievable by anonymous ftp from ftp.princeton.edu according to the instructions below. The filenames are: bbs.neur4.crepel bbs.neur4.houk bbs.neur4.kano bbs.neur4.linden bbs.neur4.simpson bbs.neur4.smith bbs.neur4.thach bbs.neur4.vincent Please do not prepare a commentary on the electronic crafts. 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