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.
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.).
E188 - E193
Wang W, Nakadate K, Masugi Tokita M, et al. Distinct cerebellar engrams in short-term and long-term motor learning. PNAS. 2014;111(1):E188-E193. doi:10.1073/pnas.1315541111
Wang, W., Nakadate, K., Masugi Tokita, M., Shutoh, F., Aziz, W., Tarusawa, E., … Shigemoto, R. (2014). Distinct cerebellar engrams in short-term and long-term motor learning. PNAS. National Academy of Sciences. https://doi.org/10.1073/pnas.1315541111
Wang, Wen, Kazuhiko Nakadate, Miwako Masugi Tokita, Fumihiro Shutoh, Wajeeha Aziz, Etsuko Tarusawa, Andrea Lörincz, et al. “Distinct Cerebellar Engrams in Short-Term and Long-Term Motor Learning.” PNAS. National Academy of Sciences, 2014. https://doi.org/10.1073/pnas.1315541111.
W. Wang et al., “Distinct cerebellar engrams in short-term and long-term motor learning,” PNAS, vol. 111, no. 1. National Academy of Sciences, pp. E188–E193, 2014.
Wang W, Nakadate K, Masugi Tokita M, Shutoh F, Aziz W, Tarusawa E, Lörincz A, Molnár E, Kesaf S, Li Y, Fukazawa Y, Nagao S, Shigemoto R. 2014. Distinct cerebellar engrams in short-term and long-term motor learning. PNAS. 111(1), E188–E193.
Wang, Wen, et al. “Distinct Cerebellar Engrams in Short-Term and Long-Term Motor Learning.” PNAS, vol. 111, no. 1, National Academy of Sciences, 2014, pp. E188–93, doi:10.1073/pnas.1315541111.
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