title: T-type channel blockade impairs long-term potentiation at the parallel fiber-Purkinje cell synapse and cerebellar learning.
abstract: CaV3.1 T-type channels are abundant at the cerebellar synapse between parallel fibers and Purkinje cells where they contribute to synaptic depolarization. So far, no specific physiological function has been attributed to these channels neither as charge carriers nor more specifically as Ca(2+) carriers. Here we analyze their incidence on synaptic plasticity, motor behavior, and cerebellar motor learning, comparing WT animals and mice where T-type channel function has been abolished either by gene deletion or by acute pharmacological blockade. At the cellular level, we show that CaV3.1 channels are required for long-term potentiation at parallel fiber-Purkinje cell synapses. Moreover, basal simple spike discharge of the Purkinje cell in KO mice is modified. Acute or chronic T-type current blockade results in impaired motor performance in particular when a good body balance is required. Because motor behavior integrates reflexes and past memories of learned behavior, this suggests impaired learning. Indeed, subjecting the KO mice to a vestibulo-ocular reflex phase reversal test reveals impaired cerebellum-dependent motor learning. These data identify a role of low-voltage activated calcium channels in synaptic plasticity and establish a role for CaV3.1 channels in cerebellar learning.
authors.affiliation: Institut de Biologie de l'Ecole Normale Supérieure, IBENS, F-75005 Paris, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Ly
authors.forename: Guy
authors.initials: G
authors.lastname: Bouvier
authors.forename: Martijn
authors.initials: M
authors.lastname: Schonewille
authors.forename: Arnaud
authors.initials: A
authors.lastname: Arabo
authors.forename: Laure
authors.initials: L
authors.lastname: Rondi-Reig
authors.forename: Clément
authors.initials: C
authors.lastname: Léna
authors.forename: Mariano
authors.initials: M
authors.lastname: Casado
authors.forename: Chris I
authors.initials: CI
authors.lastname: De Zeeuw
authors.forename: Anne
authors.initials: A
authors.lastname: Feltz
mesh_terms: D000818:Animals; D001549:Benzamides; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020747:Calcium Channels, T-Type / Q000235:genetics / Q000378:metabolism*; D002531:Cerebellum / Q000502:physiology*; D005133:Eye Movements / Q000502:physiology; D007858:Learning / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects*; D051379:Mice; D018345:Mice, Knockout; D018408:Patch-Clamp Techniques; D010880:Piperidines; D011689:Purkinje Cells / Q000378:metabolism*; D045442:Rotarod Performance Test / Q000009:adverse effects; D013569:Synapses / Q000378:metabolism*
chemical_list: C570743:3,5-dichloro-N-(1-(2,2-dimethyltetrahydropyran-4-ylmethyl)-4-fluoropiperidin-4-ylmethyl)benzamide; D001549:Benzamides; C498197:Cacna1g protein, mouse; D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D010880:Piperidines