Long-term depression as a model of cerebellar plasticity.

Long-term depression (LTD) here concerned is persistent attenuation of transmission efficiency from a bundle of parallel fibers to a Purkinje cell. Uniquely, LTD is induced by conjunctive activation of the parallel fibers and the climbing fiber that innervates that Purkinje cell. Cellular and molecular processes underlying LTD occur postsynaptically. In the 1960s, LTD was conceived as a theoretical possibility and in the 1980s, substantiated experimentally. Through further investigations using various pharmacological or genetic manipulations of LTD, a concept was formed that LTD plays a major role in learning capability of the cerebellum (referred to as "Marr-Albus-Ito hypothesis"). In this chapter, following a historical overview, recent intensive investigations of LTD are reviewed. Complex signal transduction and receptor recycling processes underlying LTD are analyzed, and roles of LTD in reflexes and voluntary movements are defined. The significance of LTD is considered from viewpoints of neural network modeling. Finally, the controversy arising from the recent finding in a few studies that whereas LTD is blocked pharmacologically or genetically, motor learning in awake behaving animals remains seemingly unchanged is examined. We conjecture how this mismatch arises, either from a methodological problem or from a network nature, and how it might be resolved.