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

Author(s): Wang, Wen; Nakadate, Kazuhiko; Masugi-Tokita, Miwako; Shutoh, Fumihiro; Aziz, Wajeeha; Tarusawa, Etsuko; Lörincz, Andrea; Molnár, Elek; Kesaf, Sebnem; Li, Yunqing; Fukazawa, Yugo; Nagao, Soichi; Shigemoto, Ryuichi
Article Title: Distinct cerebellar engrams in short-term and long-term motor learning
Affiliation IST Austria
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-termadaptation (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.
Keywords: Golgi staining; High-voltage electron microscope; Long-term depression
Journal Title: PNAS
Volume: 111
Issue 1
ISSN: 1091-6490
Publisher: National Academy of Sciences  
Date Published: 2014-01-01
Start Page: E188
End Page: E193
Sponsor: This work was supported by Solution-Oriented Research for Science and Technology from the Japan Science and Technology Agency; Ministry of Education, Culture, Sports, Science and Technology of Japan Grant 16300114 (to R.S.); Natural Science Foundation of
DOI: 10.1073/pnas.1315541111
Open access: yes (repository)