title: HCN1 channels in cerebellar Purkinje cells promote late stages of learning and constrain synaptic inhibition.
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.
authors.affiliation: M. F. Nolan: Centre for Integrative Physiology, University of Edinburgh, Hugh Robson Building, Edinburgh EH8 9XD, UK. mattnolan@ed.ac.uk.
authors.forename: Arianna
authors.initials: A
authors.lastname: Rinaldi
authors.forename: Cagla
authors.initials: C
authors.lastname: Defterali
authors.forename: Antoine
authors.initials: A
authors.lastname: Mialot
authors.forename: Derek L F
authors.initials: DL
authors.lastname: Garden
authors.forename: Mathieu
authors.initials: M
authors.lastname: Beraneck
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Nolan
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002531:Cerebellum / Q000378:metabolism / Q000502:physiology*; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000378:metabolism*; D007858:Learning / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000502:physiology; D015221:Potassium Channels / Q000378:metabolism*; D011689:Purkinje Cells / Q000378:metabolism / Q000502:physiology*; D012027:Reflex, Vestibulo-Ocular / Q000502:physiology; D013569:Synapses / Q000378:metabolism*
chemical_list: C578666:Hcn1 protein, mouse; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D015221:Potassium Channels