L-Dopa induced dyskinesias require Cholinergic Interneuron expression of Dopamine 2 receptor.

Background: Striatal Cholinergic Interneurons (CIN) are drivers of L-Dopa induced Dyskinesias (LID). However, what signaling pathways elicit aberrant CIN activity remains unclear. CIN express D2 and D5 receptors suggesting repeated activation of these receptors in response to L-Dopa could promote LID.

Dopaminergic co-transmission with sonic hedgehog inhibits abnormal involuntary movements in models of Parkinson's disease and L-Dopa induced dyskinesia.

L-Dopa induced dyskinesia (LID) is a debilitating side effect of dopamine replacement therapy for Parkinson's Disease. The mechanistic underpinnings of LID remain obscure. Here we report that diminished sonic hedgehog (Shh) signaling in the basal ganglia caused by the degeneration of midbrain dopamine neurons facilitates the formation and expression of LID.