Role of LTD in Cerebellar Motor Learning: The 75th FUJIHARA Seminar “The Cerebellum as a CNS Hub”

Synaptic plasticity provides a mechanism for learning and memory. For cerebellar motor learning, long-term depression (LTD) of synaptic transmissions from parallel fibers (PFs) to Purkinje cells (PCs) is considered the basis for motor learning, and deficiencies of both LTD and motor learning are observed in various gene-manipulated animals. Common motor learning sets, such as adaptation of the optokinetic reflex (OKR), vestibulo-ocular reflex (VOR), and rotarod test, were used for evaluation of motor learning ability. However, results obtained from the GluA2-carboxy terminus-modified knock-in mice demonstrated normal adaptation of the VOR and the OKR, despite lacking PF LTD. In that report, induction of LTD was only attempted using one type of stimulation protocol at room temperature. Thus, conditions to induce cerebellar LTD were explored in the same knock-in mutants using various protocols at near physiological temperature. Finally, we found stimulation protocols, by which LTD could be induced in these gene-manipulated mice. In this study, a set of protocols are proposed to evaluate LTD induction, which will more accurately allow examination of the causal relationship between LTD and motor learning. In conclusion, experimental conditions are crucial when evaluating LTD in gene-manipulated mice. Significance of LTD in human disease is discussed.