Fig. 2: A schematic representation of the potential role of mGlu5 receptors in the pathophysiology and treatment of PD.

In dendritic spines of striatal medium spiny neurons (MSN) of the indirect pathway, mGlu5, NMDA, and A2A receptors counteract the inhibitory activity of D2 receptors. Glial (EAAT1/2) and neuronal (EAAT3) glutamate transporters are also shown. Formation of the heteromeric complex between mGlu5 and D1 receptors in MSN of the direct pathway in response to dopaminergic denervation is shown in box. Within the heteromeric complex, D1 receptors share with mGlu5 receptors the ability to stimulate a PLCβ/ERK pathway underlying L-DOPA-induced dyskinesias (LIDs)86. For simplicity mGlu5 receptors are illustrated as monomers.