title: Distinct cerebellar engrams in short-term and long-term motor learning.
abstract: Cerebellar motor learning is suggested to be caused by long-term plasticity of excitatory parallel fiber-Purkinje cell (PF-PC) synapses associated with changes in the number of synaptic AMPA-type glutamate receptors (AMPARs). However, whether the AMPARs decrease or increase in individual PF-PC synapses occurs in physiological motor learning and accounts for memory that lasts over days remains elusive. We combined quantitative SDS-digested freeze-fracture replica labeling for AMPAR and physical dissector electron microscopy with a simple model of cerebellar motor learning, adaptation of horizontal optokinetic response (HOKR) in mouse. After 1-h training of HOKR, short-term adaptation (STA) was accompanied with transient decrease in AMPARs by 28% in target PF-PC synapses. STA was well correlated with AMPAR decrease in individual animals and both STA and AMPAR decrease recovered to basal levels within 24 h. Surprisingly, long-term adaptation (LTA) after five consecutive daily trainings of 1-h HOKR did not alter the number of AMPARs in PF-PC synapses but caused gradual and persistent synapse elimination by 45%, with corresponding PC spine loss by the fifth training day. Furthermore, recovery of LTA after 2 wk was well correlated with increase of PF-PC synapses to the control level. Our findings indicate that the AMPARs decrease in PF-PC synapses and the elimination of these synapses are in vivo engrams in short- and long-term motor learning, respectively, showing a unique type of synaptic plasticity that may contribute to memory consolidation.
authors.affiliation: Division of Cerebral Structure, National Institute for Physiological Sciences, Okazaki 444-8787, Japan.
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakadate
authors.forename: Miwako
authors.initials: M
authors.lastname: Masugi-Tokita
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Shutoh
authors.forename: Wajeeha
authors.initials: W
authors.lastname: Aziz
authors.forename: Etsuko
authors.initials: E
authors.lastname: Tarusawa
authors.forename: Andrea
authors.initials: A
authors.lastname: Lorincz
authors.forename: Elek
authors.initials: E
authors.lastname: Molnár
authors.forename: Sebnem
authors.initials: S
authors.lastname: Kesaf
authors.forename: Yun-Qing
authors.initials: YQ
authors.lastname: Li
authors.forename: Yugo
authors.initials: Y
authors.lastname: Fukazawa
authors.forename: Soichi
authors.initials: S
authors.lastname: Nagao
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Shigemoto
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D002531:Cerebellum / Q000378:metabolism*; D005614:Freeze Fracturing; D007858:Learning / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000502:physiology; D008297:Male; D008568:Memory; D008570:Memory, Short-Term / Q000502:physiology; D051379:Mice; D009046:Motor Neurons / Q000502:physiology*; D009412:Nerve Fibers / Q000473:pathology; D009473:Neuronal Plasticity; D011689:Purkinje Cells / Q000166:cytology; D018091:Receptors, AMPA / Q000378:metabolism; D013569:Synapses / Q000378:metabolism / Q000502:physiology; D009435:Synaptic Transmission; D013997:Time Factors
chemical_list: D018091:Receptors, AMPA
keywords: Golgi staining; high-voltage electron microscope; long-term depression