Principles of operation of a cerebellar learning circuit.

David J Herzfeld,Stephen G Lisberger,Marios Tringides,Nathan J Hall

doi:10.7554/elife.55217

Abstract

We provide behavioral evidence using monkey smooth pursuit eye movements for four principles of cerebellar learning. Using a circuit-level model of the cerebellum, we link behavioral data to learning's neural implementation. The four principles are: (1) early, fast, acquisition driven by climbing fiber inputs to the cerebellar cortex, with poor retention; (2) learned responses of Purkinje cells guide transfer of learning from the cerebellar cortex to the deep cerebellar nucleus, with excellent retention; (3) functionally different neural signals are subject to learning in the cerebellar cortex versus the deep cerebellar nuclei; and (4) negative feedback from the cerebellum to the inferior olive reduces the magnitude of the teaching signal in climbing fibers and limits learning. Our circuit-level model, based on these four principles, explains behavioral data obtained by strategically manipulating the signals responsible for acquisition and recall of direction learning in smooth pursuit eye movements across multiple timescales.

Highlights

A hallmark of brain function is the ability to learn and remember
The four principles of operation are: (1) early learning that occurs through a fast-learning process with poor retention, which likely employs climbing fiber mediated depression of the parallel fiber to Purkinje cell synapse; (2) over many trials, the motor memory transfers from the fast-learning process to a slow-learning process, with excellent retention, possibly in the deep cerebellar nucleus; (3) the inputs that are learned in fast- versus slowlearning processes have specific and different relationships between firing rate and eye velocity in the pursuit direction; and (4) recurrent feedback to the inferior olive from the output of the learning system modulates acquisition of learning via the fast-learning process in the cerebellar cortex
Even though our model is for cerebellar learning in pursuit eye movements, we suggest that the principles of operation are likely to generalize broadly, both to other cerebellum-dependent motor learning paradigms and to learning and memory systems elsewhere in the brain

Summary

Introduction

A hallmark of brain function is the ability to learn and remember. We can learn and successfully recall faces, events, language, concepts, places, facts, things that were frightening or rewarding, and the motor commands required to skillfully move our motor effectors. The basic currency of learning and memory is ‘plasticity’, changes in either the strength of synapses or the intrinsic excitability of a neuron’s membrane. While decades of research have identified the basic rules that govern plasticity and, for some memory systems, have even defined the neural sites that undergo plasticity, behavioral learning is not solely a property of synapses, neurons, or individual brain sites. Rather, it is the emergent property of a complete learning neural circuit in which the sites and plasticity mechanisms of learning are embedded. When we incorporate our current knowledge about the specific sites of learning and the rules of plasticity with an understanding of circuit-level interactions can we truly understand learning and memory

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