title: Silencing the majority of cerebellar granule cells uncovers their essential role in motor learning and consolidation.
abstract: Cerebellar granule cells (GCs) account for more than half of all neurons in the CNS of vertebrates. Theoretical work has suggested that the abundance of GCs is advantageous for sparse coding during memory formation. Here, we minimized the output of the majority of GCs by selectively eliminating their CaV2.1 (P/Q-type) Ca(2+) channels, which mediate the bulk of their neurotransmitter release. This resulted in reduced GC output to Purkinje cells (PCs) and stellate cells (SCs) as well as in impaired long-term plasticity at GC-PC synapses. As a consequence modulation amplitude and regularity of simple spike (SS) output were affected. Surprisingly, the overall motor performance was intact, whereas demanding motor learning and memory consolidation tasks were compromised. Our findings indicate that a minority of functionally intact GCs is sufficient for the maintenance of basic motor performance, whereas acquisition and stabilization of sophisticated memories require higher numbers of normal GCs controlling PC firing.
authors.affiliation: Department of Neuroscience, Erasmus MC Rotterdam, 3015GE Rotterdam, The Netherlands.
authors.forename: Elisa
authors.initials: E
authors.lastname: Galliano
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Gao
authors.forename: Martijn
authors.initials: M
authors.lastname: Schonewille
authors.forename: Boyan
authors.initials: B
authors.lastname: Todorov
authors.forename: Esther
authors.initials: E
authors.lastname: Simons
authors.forename: Andreea S
authors.initials: AS
authors.lastname: Pop
authors.forename: Egidio
authors.initials: E
authors.lastname: D'Angelo
authors.forename: Arn M J M
authors.initials: AM
authors.lastname: van den Maagdenberg
authors.forename: Freek E
authors.initials: FE
authors.lastname: Hoebeek
authors.forename: Chris I
authors.initials: CI
authors.lastname: De Zeeuw
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D020864:Calcium Channels, N-Type / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002531:Cerebellum / Q000502:physiology*; D020868:Gene Silencing; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology*; D009473:Neuronal Plasticity; D009474:Neurons / Q000502:physiology; D011689:Purkinje Cells / Q000502:physiology; D013569:Synapses / Q000502:physiology
chemical_list: D020864:Calcium Channels, N-Type