MetaTOC stay on top of your field, easily

HCN1 channels in cerebellar Purkinje cells promote late stages of learning and constrain synaptic inhibition

, , , , ,

The Journal of Physiology

Published online on

Abstract

•  Purkinje cells in the cerebellum are important for motor learning and have electrical signalling properties determined by several different types of ion channel. •  Using a restricted genetic deletion, we investigate the roles of HCN1 ion channels expressed by cerebellar Purkinje cells. •  This deletion causes specific learning impairments in a subset of behaviours to which Purkinje cells contribute. •  At a cellular level this specificity of function is mirrored by increases in the duration of responses to inhibitory synaptic input, without changes in responses to excitatory synaptic input activated in the absence of inhibition. •  The results help us to understand how behaviours are influenced by ion channels important for aspects of computation in a defined neuronal cell type. Abstract  Neural computations rely on ion channels that modify neuronal responses to synaptic inputs. While single cell recordings suggest diverse and neurone type‐specific computational functions for HCN1 channels, their behavioural roles in any single neurone type are not clear. Using a battery of behavioural assays, including analysis of motor learning in vestibulo‐ocular reflex and rotarod tests, we find that deletion of HCN1 channels from cerebellar Purkinje cells selectively impairs late stages of motor learning. Because deletion of HCN1 modifies only a subset of behaviours involving Purkinje cells, we asked whether the channel also has functional specificity at a cellular level. We find that HCN1 channels in cerebellar Purkinje cells reduce the duration of inhibitory synaptic responses but, in the absence of membrane hyperpolarization, do not affect responses to excitatory inputs. Our results indicate that manipulation of subthreshold computation in a single neurone type causes specific modifications to behaviour.