title: Memory trace of motor learning shifts transsynaptically from cerebellar cortex to nuclei for consolidation.
abstract: Adaptation of ocular reflexes is a prototype of motor learning. While the cerebellum is acknowledged as the critical site for motor learning, the functional differences between the cerebellar cortex and nuclei in motor memory formation are not precisely known. Two different views are proposed: one that the memory is formed within the cerebellar flocculus, and the other that the memory is formed within vestibular nuclei. Here we developed a new paradigm of long-term adaptation of mouse horizontal optokinetic response eye movements and examined the location of its memory trace. We also tested the role of flocculus and inferior olive in long-term adaptation by chronic lesion experiments. Reversible bilateral flocculus shutdown with local application of 0.5 microl-5% lidocaine extinguished the memory trace of day-long adaptation, while it very little affected the memory trace of week-long adaptation. The responsiveness of vestibular nuclei after week-long adaptation was examined by measuring the extracellular field responses to the electrical stimulation of vestibular nerve under trichloroacetaldehyde anesthesia. The amplitudes and slopes of evoked monosynaptic field response (N1) of week-long adapted mice were enhanced around the medial vestibular nucleus compared with those of control mice. Chronic flocculus or inferior olive lesions abolished both day and week-long adaptations. These results suggest that the functional memory trace of short-term adaptation is formed initially within the cerebellar cortex, and later transferred to vestibular nuclei to be consolidated to a long-term memory. Both day and week-long adaptations were markedly depressed when neural nitric oxide was pharmacologically blocked locally and when neuronal nitric oxide synthase was ablated by gene knockout, suggesting that cerebellar long-term depression underlies both acquisition and consolidation of motor memory.
authors.affiliation: Laboratory for Motor Learning Control, RIKEN Brain Science Institute, Hirosawa 2-1, Wako, Saitama 351-0198, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Shutoh
authors.forename: M
authors.initials: M
authors.lastname: Ohki
authors.forename: H
authors.initials: H
authors.lastname: Kitazawa
authors.forename: S
authors.initials: S
authors.lastname: Itohara
authors.forename: S
authors.initials: S
authors.lastname: Nagao
mesh_terms: D000222:Adaptation, Physiological; D000779:Anesthetics, Local; D000818:Animals; D001522:Behavior, Animal; D002525:Cerebellar Cortex / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005133:Eye Movements / Q000502:physiology*; D005427:Flocculation; D007858:Learning / Q000502:physiology*; D008012:Lidocaine / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D052248:Nitric Oxide Synthase Type I / Q000172:deficiency; D017120:Nystagmus, Optokinetic / Q000502:physiology; D009847:Olivary Nucleus / Q000293:injuries / Q000502:physiology; D012027:Reflex, Vestibulo-Ocular / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D013997:Time Factors; D014726:Vestibular Nuclei / Q000187:drug effects / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D000779:Anesthetics, Local; D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D008012:Lidocaine; D052248:Nitric Oxide Synthase Type I