期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：11
页码：3541-3546
DOI：10.1073/pnas.1413798112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceAn efficient way to form a new declarative memory is to repeat a short-term training many times with a rest between the training sessions, because the learned memory is consolidated after training. This suggests that the brain still keeps actively working even after training, but the synaptic dynamics during posttraining periods has been studied rarely. The posttraining memory consolidation is also observed in cerebellar motor learning. To investigate the mechanism, we formulated a simple theoretical model of the cerebellum with a minimal number of elements and learning-related changes in synaptic efficacy at multiple locations. Computer simulations with this model closely reproduced learning behavior for oculomotor reflexes in wild-type mice and explained peculiar learning behavior in genetically manipulated mice. Long-term depression (LTD) at parallel fiber-Purkinje cell (PF-PC) synapses is thought to underlie memory formation in cerebellar motor learning. Recent experimental results, however, suggest that multiple plasticity mechanisms in the cerebellar cortex and cerebellar/vestibular nuclei participate in memory formation. To examine this possibility, we formulated a simple model of the cerebellum with a minimal number of components based on its known anatomy and physiology, implementing both LTD and long-term potentiation (LTP) at PF-PC synapses and mossy fiber-vestibular nuclear neuron (MF-VN) synapses. With this model, we conducted a simulation study of the gain adaptation of optokinetic response (OKR) eye movement. Our model reproduced several important aspects of previously reported experimental results in wild-type and cerebellum-related gene-manipulated mice. First, each 1-h training led to the formation of short-term memory of learned OKR gain at PF-PC synapses, which diminished throughout the day. Second, daily repetition of the training gradually formed long-term memory that was maintained for days at MF-VN synapses. We reproduced such memory formation under various learning conditions. Third, long-term memory formation occurred after training but not during training, indicating that the memory consolidation occurred during posttraining periods. Fourth, spaced training outperformed massed training in long-term memory formation. Finally, we reproduced OKR gain changes consistent with the changes in the vestibuloocular reflex (VOR) previously reported in some gene-manipulated mice.
关键词：cerebellum ; plasticity ; memory consolidation ; posttraining period ; Marr–Albus–Ito theory
