Beyond neural coding? Lessons from perceptual control theory

Pointing to similarities between challenges encountered in today's neural coding and twentieth-century behaviorism, we draw attention to lessons learned from resolving the latter. In particular, Perceptual Control Theory posits behavior as a closed-loop control process with immediate and teleological causes. With two examples, we illustrate how these ideas may also address challenges facing current neural coding paradigms

Modeling the Cerebellar Microcircuit: New Strategies for a Long-Standing Issue

The cerebellar microcircuit has been the work bench for theoretical and computational modeling since the beginning of neuroscientific research. The regular neural architecture of the cerebellum inspired different solutions to the long-standing issue of how its circuitry could control motor learning and coordination. Originally, the cerebellar network was modeled using a statistical-topological approach that was later extended by considering the geometrical organization of local microcircuits. However, with the advancement in anatomical and physiological investigations, new discoveries have revealed an unexpected richness of connections, neuronal dynamics and plasticity, calling for a change in modeling strategies, so as to include the multitude of elementary aspects of the network into an integrated and easily updatable computational framework. Recently, biophysically accurate realistic models using a bottom-up strategy accounted for both detailed connectivity and neuronal non-linear membrane dynamics. In this perspective review, we will consider the state of the art and discuss how these initial efforts could be further improved. Moreover, we will consider how embodied neurorobotic models including spiking cerebellar networks could help explaining the role and interplay of distributed forms of plasticity. We envisage that realistic modeling, combined with closed-loop simulations, will help to capture the essence of cerebellar computations and could eventually be applied to neurological diseases and neurorobotic control systems

Attentive Learning of Sequential Handwriting Movements: A Neural Network Model

Defense Advanced research Projects Agency and the Office of Naval Research (N00014-95-1-0409, N00014-92-J-1309); National Science Foundation (IRI-97-20333); National Institutes of Health (I-R29-DC02952-01)

The perceptual shaping of anticipatory actions

Humans display anticipatory motor responses to minimize the adverse effects of predictable perturbations. A widely accepted explanation for this behaviour relies on the notion of an inverse model that, learning from motor errors, anticipates corrective responses. Here, we propose and validate the alternative hypothesis that anticipatory control can be realized through a cascade of purely sensory predictions that drive the motor system, reflecting the causal sequence of the perceptual events preceding the error. We compare both hypotheses in a simulated anticipatory postural adjustment task. We observe that adaptation in the sensory domain, but not in the motor one, supports the robust and generalizable anticipatory control characteristic of biological systems. Our proposal unites the neurobiology of the cerebellum with the theory of active inference and provides a concrete implementation of its core tenets with great relevance both to our understanding of biological control systems and, possibly, to their emulation in complex artefacts

Learning Related Regulation of a Voltage-Gated Ion Channel in the Cerebellum

The neural mechanisms that support learning and memory are still poorly understood. Much work has focused on changes in neurotransmitter receptor expression, while changes in voltage-gated ion channel expression have been largely unexplored, despite the fact that voltage-gated ion channels govern neuronal excitability. Here we used eyeblink conditioning (EBC) in rats, a model of learning and memory with a well-understood neural circuit, to examine regulation of voltage-gated ion channels as a consequence of learning. EBC is a form of classical conditioning that involves pairings of a behaviorally neutral conditioned stimulus (CS) and an eyeblink eliciting unconditioned stimulus (US) over many trials to produce an eyeblink conditioned response (CR) to the CS in anticipation of the US. The acquisition and generation of the eyeblink CR is governed by plasticity at various sites in the cerebellum, both in the cerebellar cortex and the interpositus nucleus (IPN). Purkinje cells (PCs) are the primary neuron in the cerebellar cortex and these cells represent the sole output of the cerebellar cortex. PCs tonically inhibit the neurons of the IPN; the IPN is the start of the eyeblink pathway. In order for a CR to be generated, the inhibition of the IPN by PCs must be lifted. Basket cells (BCs) are small inhibitory interneurons that form synapses near the PC soma. These neurons are strategically located to strongly regulate PC output through inhibitory input near the axon hillock. BC axon terminals have the highest expression of Kv1.2, an alpha subunit of the Kv1 (Shaker) family of voltage-gated potassium channels, in the cerebellum. In addition, significant Kv1.2 expression is found on PC dendrites. Blocking Kv1.2 leads to increased GABAergic input to PCs and facilitates EBC. In the current work, we addressed the question of whether EBC itself regulates surface expression of Kv1.2 in cerebellar cortex. Rats received three days of either EBC, explicitly unpaired stimulus presentations, or no stimuli, and cerebellar tissue was harvested and analyzed via biotinylation/western blot (WB) and multiphoton microscopy (MP) techniques. In the first experiment, the Unpaired group showed significantly reduced surface Kv1.2 expression at BC axon terminals as measured by MP, but no changes observed with the WB measure, which measures expression at both BC axon terminals and PC dendrites. The second experiment used the same procedures but examined cerebellar tissue following a shorter training procedure. We hypothesized that the Paired and Unpaired groups would show similar Kv1.2 surface expression earlier in training. The Unpaired group showed increased surface Kv1.2 compared to the other two groups in the WB measures, but no differences were observed in the MP measure. Paired group rats that did not exhibit CRs showed the same pattern as the Unpaired group. Overall, we observed training and location specific changes in surface Kv1.2 expression, suggesting that learning does appear to regulate voltage-gated ion channel expression in the mammalian brain. Increased surface Kv1.2 early in training before CR expression emerges may set the stage for other mechanisms to govern the expression of the learned response. Prolonged stimulus input that is unmodulated by expression of a learned response, such as in the Unpaired group in the first experiment, leads to long-term changes in surface Kv1.2 expression exclusively at BC axon terminals

Spinocerebellar Ataxia

This book is about spinocerebellar ataxia (SCA), which is among the most challenging pathologies in the neurological landscape. It covers basic concepts, functional classification, and new approaches to medical and non-medical treatment including rehabilitation/palliative care approaches. The volume also describes a wide spectrum of generalities and particularities about various forms of clinical and genetic presentations of ACS that have life-threatening characteristics and long-standing presentation with tremendous variability in presentation and clinical severity. In addition, the book presents important aspects of cerebellar anatomy, nutrition impact, genetic subtypes, and functional classification of medical and non-medical interventions related to stem cells, rehabilitation, and palliative care

Spatio-Temporal and Multisensory Integration: the relationship between sleep and the cerebellum

Does the cerebellum sleep? If so, does sleep contribute to cerebellar cognition? In this thesis, the sleep contribution to the consolidation process of spatial-temporal and multisensory integration was investigated in relation to the human cerebellum. Multiple experimental approaches were used to answer research questions addressed in the various chapters. Summarizing the evidence of the electrophysiology and neuroimaging studies, in Chapter1 we present intriguing evidence that the cerebellum is involved in sleep physiology, and that cerebellar-dependent memory formation can be consolidated during sleep. In Chapter 2, using functional neuroimaging in healthy participants during various forms of the Serial interception sequential learning (SISL) task, i.e., predictive timing, motor coordination, and motor imagination, we assessed the cerebellar involvement in spatio-temporal predictive timing; and possible cerebellar interactions with other regions, most notably the hippocampus. In Chapter 3, we add to the findings of Chapter 2 that indicate the cerebellum and hippocampus are involved in the task, by showing that more than simply activated, the cerebellum is a necessary and responsible region for the establishment of the spatio-temporal prediction. This follows from the deficits in behavioral properties of the predictive and reactive timing in the cerebellar ataxia type 6 patients, using the modified version of the SISL task. In Chapter 4, we assessed the subsequent post-interval behavioral performances on the learning of the fixed and random timing sequences in the SISL task, comparing a sleep group and wake group in healthy participants. Our findings show that sleep consolidates the process of cerebellar-dependent spatio-temporal integration. In Chapter 5, we investigated the establishment of visual-tactile integration during sleep through the examination of tactile motion stimulation during sleep and showed that, subsequent to sleep, directional visual motion discrimination i