title: Burst-Dependent Bidirectional Plasticity in the Cerebellum Is Driven by Presynaptic NMDA Receptors.
abstract: Numerous studies have shown that cerebellar function is related to the plasticity at the synapses between parallel fibers and Purkinje cells. How specific input patterns determine plasticity outcomes, as well as the biophysics underlying plasticity of these synapses, remain unclear. Here, we characterize the patterns of activity that lead to postsynaptically expressed LTP using both in vivo and in vitro experiments. Similar to the requirements of LTD, we find that high-frequency bursts are necessary to trigger LTP and that this burst-dependent plasticity depends on presynaptic NMDA receptors and nitric oxide (NO) signaling. We provide direct evidence for calcium entry through presynaptic NMDA receptors in a subpopulation of parallel fiber varicosities. Finally, we develop and experimentally verify a mechanistic plasticity model based on NO and calcium signaling. The model reproduces plasticity outcomes from data and predicts the effect of arbitrary patterns of synaptic inputs on Purkinje cells, thereby providing a unified description of plasticity.
authors.affiliation: Ecole Normale Supérieure, Institut de Biologie de l'ENS (IBENS), Inserm U1024, CNRS UMR 8197, Paris 75005, France.
authors.forename: Guy
authors.initials: G
authors.lastname: Bouvier
authors.affiliation: Ecole Normale Supérieure, Institut de Biologie de l'ENS (IBENS), Inserm U1024, CNRS UMR 8197, Paris 75005, France; Departments of Statistics and Neurobiology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: David
authors.initials: D
authors.lastname: Higgins
authors.affiliation: Ecole Normale Supérieure, Institut de Biologie de l'ENS (IBENS), Inserm U1024, CNRS UMR 8197, Paris 75005, France.
authors.forename: Maria
authors.initials: M
authors.lastname: Spolidoro
authors.affiliation: Ecole Normale Supérieure, Institut de Biologie de l'ENS (IBENS), Inserm U1024, CNRS UMR 8197, Paris 75005, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Carrel
authors.affiliation: Ecole Normale Supérieure, Institut de Biologie de l'ENS (IBENS), Inserm U1024, CNRS UMR 8197, Paris 75005, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Mathieu
authors.affiliation: Ecole Normale Supérieure, Institut de Biologie de l'ENS (IBENS), Inserm U1024, CNRS UMR 8197, Paris 75005, France.
authors.forename: Clément
authors.initials: C
authors.lastname: Léna
authors.affiliation: Ecole Normale Supérieure, Institut de Biologie de l'ENS (IBENS), Inserm U1024, CNRS UMR 8197, Paris 75005, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Dieudonné
authors.affiliation: Ecole Normale Supérieure, Institut de Biologie de l'ENS (IBENS), Inserm U1024, CNRS UMR 8197, Paris 75005, France.
authors.forename: Boris
authors.initials: B
authors.lastname: Barbour
authors.affiliation: Departments of Statistics and Neurobiology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Brunel
authors.affiliation: Ecole Normale Supérieure, Institut de Biologie de l'ENS (IBENS), Inserm U1024, CNRS UMR 8197, Paris 75005, France. Electronic address: casado@biologie.ens.fr.
authors.forename: Mariano
authors.initials: M
authors.lastname: Casado
mesh_terms: D000200:Action Potentials; D000818:Animals; D020013:Calcium Signaling; D019706:Excitatory Postsynaptic Potentials; D017774:Long-Term Potentiation; D051379:Mice; D008810:Mice, Inbred C57BL; D008959:Models, Neurological; D009569:Nitric Oxide / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000502:physiology; D011689:Purkinje Cells / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide