title: Inhibition promotes long-term potentiation at cerebellar excitatory synapses.
abstract: The ability of the cerebellar cortex to learn from experience ensures the accuracy of movements and reflex adaptation, processes which require long-term plasticity at granule cell (GC) to Purkinje neuron (PN) excitatory synapses. PNs also receive GABAergic inhibitory inputs via GCs activation of interneurons; despite the involvement of inhibition in motor learning, its role in long-term plasticity is poorly characterized. Here we reveal a functional coupling between ionotropic GABAA receptors and low threshold CaV3 calcium channels in PNs that sustains calcium influx and promotes long-term potentiation (LTP) at GC to PN synapses. High frequency stimulation induces LTP at GC to PN synapses and CaV3-mediated calcium influx provided that inhibition is intact; LTP is mGluR1, intracellular calcium store and CaV3 dependent. LTP is impaired in CaV3.1 knockout mice but it is nevertheless recovered by strengthening inhibitory transmission onto PNs; promoting a stronger hyperpolarization via GABAA receptor activation leads to an enhanced availability of an alternative Purkinje-expressed CaV3 isoform compensating for the lack of CaV3.1 and restoring LTP. Accordingly, a stronger hyperpolarization also restores CaV3-mediated calcium influx in PNs from CaV3.1 knockout mice. We conclude that by favoring CaV3 channels availability inhibition promotes LTP at cerebellar excitatory synapses.
authors.affiliation: Institute of Cellular and Integrative Neurosciences, CNRS, 5 Rue Blaise Pascal 67084 Strasbourg, France.
authors.forename: F
authors.initials: F
authors.lastname: Binda
authors.affiliation: Institute of Cellular and Integrative Neurosciences, CNRS, 5 Rue Blaise Pascal 67084 Strasbourg, France.
authors.forename: K
authors.initials: K
authors.lastname: Dorgans
authors.affiliation: Chronobiotron UMS 3415, 5 Rue Blaise Pascal 67084 Strasbourg, France.
authors.forename: S
authors.initials: S
authors.lastname: Reibel
authors.affiliation: Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Sakimura
authors.affiliation: Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kano
authors.affiliation: Institute of Cellular and Integrative Neurosciences, CNRS, 5 Rue Blaise Pascal 67084 Strasbourg, France.
authors.forename: B
authors.initials: B
authors.lastname: Poulain
authors.affiliation: Institute of Cellular and Integrative Neurosciences, CNRS, 5 Rue Blaise Pascal 67084 Strasbourg, France.|University of Strasbourg, 5 Rue Blaise Pascal 67084 Strasbourg, France.
authors.forename: P
authors.initials: P
authors.lastname: Isope
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D002531:Cerebellum / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D011689:Purkinje Cells / Q000502:physiology; D011963:Receptors, GABA-A / Q000378:metabolism; D013569:Synapses / Q000502:physiology*
chemical_list: D015220:Calcium Channels; D011963:Receptors, GABA-A; D002118:Calcium