@article{1920, 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.}, author = {Wang, Wen and Nakadate, Kazuhiko and Masugi Tokita, Miwako and Shutoh, Fumihiro and Aziz, Wajeeha and Tarusawa, Etsuko and Lörincz, Andrea and Molnár, Elek and Kesaf, Sebnem and Li, Yunqing and Fukazawa, Yugo and Nagao, Soichi and Shigemoto, Ryuichi}, journal = {PNAS}, number = {1}, pages = {E188 -- E193}, publisher = {National Academy of Sciences}, title = {{Distinct cerebellar engrams in short-term and long-term motor learning}}, doi = {10.1073/pnas.1315541111}, volume = {111}, year = {2014}, } @article{1919, abstract = {Long-lasting memories are formed when the stimulus is temporally distributed (spacing effect). However, the synaptic mechanisms underlying this robust phenomenon and the precise time course of the synaptic modifications that occur during learning remain unclear. Here we examined the adaptation of horizontal optokinetic response in mice that underwent 1 h of massed and spaced training at varying intervals. Despite similar acquisition by all training protocols, 1 h of spacing produced the highest memory retention at 24 h, which lasted for 1 mo. The distinct kinetics of memory are strongly correlated with the reduction of floccular parallel fiber-Purkinje cell synapses but not with AMPA receptor (AMPAR) number and synapse size. After the spaced training, we observed 25%, 23%, and 12% reduction in AMPAR density, synapse size, and synapse number, respectively. Four hours after the spaced training, half of the synapses and Purkinje cell spines had been eliminated, whereas AMPAR density and synapse size were recovered in remaining synapses. Surprisingly, massed training also produced long-term memory and halving of synapses; however, this occurred slowly over days, and the memory lasted for only 1 wk. This distinct kinetics of structural plasticity may serve as a basis for unique temporal profiles in the formation and decay of memory with or without intervals.}, author = {Aziz, Wajeeha and Wang, Wen and Kesaf, Sebnem and Mohamed, Alsayed and Fukazawa, Yugo and Shigemoto, Ryuichi}, journal = {PNAS}, number = {1}, pages = {E194 -- E202}, publisher = {National Academy of Sciences}, title = {{Distinct kinetics of synaptic structural plasticity, memory formation, and memory decay in massed and spaced learning}}, doi = {10.1073/pnas.1303317110}, volume = {111}, year = {2014}, }