Modeling memory consolidation during posttraining periods in cerebellovestibular learning

Abstract

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.