Rescue of striatal long-term depression by chronic MGLU5 receptor negative allosteric modulation in distinct dystonia models

Abstract

An impairment of long-term synaptic plasticity is a peculiar endophenotype of distinct forms of dystonia. We previously demonstrated a complete loss of corticostriatal long-term synaptic depression (LTD) in rodent models of two distinct isolated dystonias, resulting from mutations in the TOR1A (DYT1), and GNAL (DYT25) genes. Broad-spectrum antimuscarinic drugs are used to counteract abnormal striatal acetylcholine-mediated transmission, which plays a crucial role in dystonia pathophysiology. The aberrant excitability of striatal cholinergic cells can also be modulated by group I metabotropic glutamate receptor subtypes.