Neural instructive signals for associative cerebellar learning

Abstract

Supervised learning depends on instructive signals that shape the output of neural circuits to support learned changes in behavior. Climbing fiber inputs to the cerebellar cortex represent one of the strongest candidates in the vertebrate brain for conveying neural instructive signals. However, recent studies have shown that Purkinje cell stimulation can also drive cerebellar learning, and the relative importance of these two neuron types in providing instructive signals for cerebellum-dependent behaviors remains unresolved. Here we used cell-type specific perturbations of climbing fibers, Purkinje cells, and other cerebellar circuit elements to systematically evaluate their contributions to delay eyeblink conditioning. Our findings reveal that while optogenetic stimulation of either climbing fibers or Purkinje cells are capable of driving learning under some conditions, even subtle reductions in climbing fiber signaling completely block learning to natural conditioning stimuli. We conclude that climbing fibers and corresponding Purkinje cell complex-spike events provide essential instructive signals for associative cerebellar learning.