mGluR1 in Cerebellar Purkinje Cells Essential for Long-Term Depression, Synapse Elimination, and Motor Coordination

TLDR

Deletion of mGluR1 disrupts cerebellar development and function. The study aims to determine whether mGluR1 in Purkinje cells is essential for synapse formation, plasticity, and motor control. A Purkinje‑cell–specific mGluR1α transgene was expressed in mGluR1‑knockout mice. Rescue of mGluR1 restored long‑term depression, climbing‑fiber regression, and dose‑dependent motor coordination in knockout mice.

Abstract

Targeted deletion of metabotropic glutamate receptor–subtype 1 (mGluR1) gene can cause defects in development and function in the cerebellum. We introduced the mGluR1α transgene into mGluR1-null mutant [mGluR1 (–/–)] mice with a Purkinje cell (PC)–specific promoter. mGluR1-rescue mice showed normal cerebellar long-term depression and regression of multiple climbing fiber innervation, events significantly impaired in mGluR1 (–/–) mice. The impaired motor coordination was rescued by this transgene, in a dose-dependent manner. We propose that mGluR1 in PCs is a key molecule for normal synapse formation, synaptic plasticity, and motor control in the cerebellum.