Distinct cerebellar engrams in short-term and long-term motor learning

Wang, Wen, Nakadate, Kazuhiko, Masugi-Tokita, Miwako, Shutoh, Fumihiro, Aziz, Wajeeha, Tarusawa, Etsuko, Lorincz, Andrea, Molnár, Elek, Kesaf, Sebnem, Li, Yun-Qing, Fukazawa, Yugo, Nagao, Soichi and Shigemoto, Ryuichi (2014) Distinct cerebellar engrams in short-term and long-term motor learning. Proceedings of the National Academy of Sciences, 111 (1). E188-93. ISSN 1091-6490

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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.

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Neuroscience
Research Centres and Groups: Sussex Neuroscience
Depositing User: Wajeeha Aziz
Date Deposited: 23 Oct 2017 14:58
Last Modified: 23 Oct 2017 14:58
URI: http://sro.sussex.ac.uk/id/eprint/70611
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