RIM4 deficiency leads to reduced somato-dendritic excitability of cerebellar Purkinje cells

Abstract

Synaptic function is determined by the release machinery at the active zone which is composed of a large number of synaptic proteins including RIMs. The large RIMs are key components of the presynaptic active zone that ubiquitously modulate both excitatory and inhibitory neurotransmitter release. In contrast, the function of smaller RIMs in the central nervous system is not much known. In this study, a novel function of RIM4 is demonstrated. RIM4 is dispensable for neurotransmitter release but plays a postsynaptic and cell-type specific role in cerebellar Purkinje cells that is essential for normal motor function. Mice lacking RIM4 display a disturbed Purkinje cell intrinsic firing properties, a megascopic alteration in the cerebellar morphology, and aberrant calcium signaling in Purkinje cells. Also, the specific alterations in Purkinje cell signaling which are demonstrated in this study might provide new insights that could elucidate the physiological mechanism of ataxia phenotype in mice.