Abstract

High-fidelity regulation of information transmission among cerebellar layers is mainly provided by synaptic plasticity. Therefore, determining the regulatory foundations of synaptic plasticity in the cerebellum and translating them to behavioral output are of great importance. To date, many experimental studies have been carried out in order to clarify the effect of synaptic defects, while targeting a specific signaling pathway in the cerebellar function. However, the contradictory results of these studies at the behavioral level further add to the ambiguity of the problem. Information transmission through firing rate changes in populations of interconnected neurons is one of the most widely accepted principles of neural coding. In this study, while considering the efficacy of synaptic interactions among the cerebellar layers, we propose a firing rate model to realize the concept of transmission coefficient. Thereafter, using a computational approach, we test the effect of different values of transmission coefficient on the gain adaptation of a cerebellar-dependent motor learning task. In conformity with the behavioral data, the proposed model can accurately predict that disruption in different forms of synaptic plasticity does not have the same effect on motor learning. Specifically, impairment in training mechanisms, like in the train-induced LTD in parallel fiber-Purkinje cell synapses, has a significant negative impact on all aspects of learning, including memory formation, transfer, and consolidation, although it does not disrupt basic motor performance. In this regard, the overinduction of parallel fiber-molecular layer interneuron LTP could not prevent motor learning impairment, despite its vital role in preserving the robustness of basic motor performance. In contrast, impairment in plasticity induced by interneurons and background activity of climbing fibers is partly compensable through overinduction of train-induced parallel fiber-Purkinje cell LTD. Additionally, blockade of climbing fiber signaling to the cerebellar cortex, referred to as olivary system lesion, shows the most destructive effect on both motor learning and basic motor performance. Overall, the obtained results from the proposed computational framework are used to provide a map from procedural motor memory formation in the cerebellum. Certainly, the generalization of this concept to other multi-layered networks of the brain requires more physiological and computational researches.

Highlights

  • The cytoarchitecture of the cerebellar cortex has a uniform character and is roughly divided into three parallel circuit elements (Marzban et al, 2015), which, from the inner to the outer layer, are called the granular, the Purkinje, and the molecular layers (Figure 1A)

  • Each panel consists of the learning curve(s) of optokinetic reflex (OKR) gain at the top and its corresponding time-dependent changes in weights of PFPC (W{parallel fibers (PFs)−Purkinje cells (PCs)}), PF-molecular layer interneurons (MLIs) (W{PF−MLI}), and mossy fibers’ (MFs)-deep nuclei (DN) (W{MF−DN}) synapses at the bottom view

  • The rapid changes are related to the fast dynamic (W{PF−PC}) and the gradual low changes at the end of each day relative to the start of the same day are attributed to slow dynamic (W{MF−DN})

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Summary

Introduction

The cytoarchitecture of the cerebellar cortex has a uniform character and is roughly divided into three parallel circuit elements (Marzban et al, 2015), which, from the inner to the outer layer, are called the granular, the Purkinje, and the molecular layers (Figure 1A). Effective communication between these layers is mainly regulated by synapses (Evans, 2007). An individual type of plasticity alone cannot account for wide dynamic ranges of cerebellar learning (Boyden et al, 2004; Solouki and Pooyan, 2016)

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