Feedback control in the olivo-cerebellar loop

Abstract

About 40 years ago, a subpopulation of small neurons in the deep cerebellar nuclei were shown to project to the inferior olive, the source of the climbing fiber input to the cerebellum. This nucleo-olivary projection follows the zonal and probably also microzonal arrangement of the cerebellum so that closed loops are formed between the neurons in the olive, the cerebellar cortex, and the deep nuclei. Although it was first thought to be excitatory, it was independently shown that the cells were GABAergic and that activity in the nucleo-olivary pathway inhibits olivary activity. A number of functions have been suggested for this inhibition: (a) feedback control of learning, (b) gating of olivary input in general, and (c) feedback control of background activity in Purkinje cells. Evidence is consistent with (a) and (c). Activity in the nucleo-olivary pathway suppresses both synaptic transmission and background activity in the olive. When conditioned blink responses develop, the blink-related part of the olive is inhibited. When the nucleo-olivary pathway is interrupted, there is a corresponding increase in complex spike discharge in Purkinje cells followed by a strong suppression of simple spike firing. Stimulation of the pathway has the opposite results. It is concluded that the nucleo-olivary fibers are inhibitory and that they form a number of independent feedback loops, each one specific for a microcomplex, in a system that regulates cerebellar learning as well as spontaneous activity in the cerebello-olivocerebellar circuit. Besides these inhibitory effects, it has been argued that the nucleo-olivary pathway regulates electrotonic coupling between olivary cells.