title: Long-term potentiation of inhibitory synaptic transmission onto cerebellar Purkinje neurons contributes to adaptation of vestibulo-ocular reflex.
abstract: Synaptic plasticity in the cerebellum is thought to contribute to motor learning. In particular, long-term depression (LTD) at parallel fiber (PF) to Purkinje neuron (PN) excitatory synapses has attracted much attention of neuroscientists as a primary cellular mechanism for motor learning. In contrast, roles of plasticity at cerebellar inhibitory synapses in vivo remain unknown. Here, we have investigated the roles of long-lasting enhancement of transmission at GABAergic synapses on a PN that is known as rebound potentiation (RP). Previous studies demonstrated that binding of GABAA receptor with GABAA receptor-associated protein (GABARAP) is required for RP, and that a peptide that blocks this binding suppresses RP induction. To address the functional roles of RP, we generated transgenic mice that express this peptide fused to a fluorescent protein selectively in PNs using the PN-specific L7 promoter. These mice failed to show RP, although they showed no changes in the basal amplitude or frequency of miniature IPSCs. The transgenic mice also showed no abnormality in gross cerebellar morphology, LTD, or other excitatory synaptic properties, or intrinsic excitability of PNs. Next, we attempted to evaluate their motor control and learning ability by examining reflex eye movements. The basal dynamic properties of the vestibulo-ocular reflex and optokinetic response, and adaptation of the latter, were normal in the transgenic mice. In contrast, the transgenic mice showed defects in the adaptation of vestibulo-ocular reflex, a model paradigm of cerebellum-dependent motor learning. These results together suggest that RP contributes to a certain type of motor learning.
authors.affiliation: Department of Biophysics, Graduate School of Science, Kyoto University, Kyoto 606-8502, Japan, Graduate School of Brain Science, Doshisha University, Kyoto 619-0225, Japan, and Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Tanaka
authors.forename: Shin-Ya
authors.initials: SY
authors.lastname: Kawaguchi
authors.forename: Go
authors.initials: G
authors.lastname: Shioi
authors.forename: Tomoo
authors.initials: T
authors.lastname: Hirano
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D053444:Inhibitory Postsynaptic Potentials; D017774:Long-Term Potentiation; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins; D055369:Miniature Postsynaptic Potentials; D011689:Purkinje Cells / Q000378:metabolism / Q000502:physiology*; D012027:Reflex, Vestibulo-Ocular; D013569:Synapses / Q000378:metabolism / Q000502:physiology
chemical_list: D051017:Apoptosis Regulatory Proteins; D003598:Cytoskeletal Proteins; C480861:GABARAP protein, mouse; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins