Role of Striatal Cholinergic Interneurons in Parkinson’s Disease Dyskinesia

Study Rationale:                   
In pre-clinical models, we identified an important role of cholinergic interneurons — which release the neurotransmitter acetylcholine — from part of the brain called the striatum in levodopa-induced dyskinesia. This small population of striatal neurons has not been well studied and may present a new therapeutic target.

Hypothesis:
We hypothesize that modulating the activities of striatal cholinergic interneurons can alter dyskinesia.

Study Design:
We will test methods to modulate the effect of cholinergic neuronal activity by expressing genetically modified receptors. We will inhibit the neuronal activity and study if dyskinesia can be prevented or reduced.

Impact on Diagnosis/Treatment of Parkinson’s Disease:             
This study will provide a functional evidence for importance of cholinergic interneurons in dyskinesia treatment. Treatment of Parkinson’s disease has been advanced by pharmacological approaches and modulation of specific areas of the brain using lesions or deep brain stimulation. Cell type-specific modulation could provide the next generation of refined therapeutic approaches.

Next Steps for Development:
Once the functional role of cholinergic interneurons is firmly established, we will explore therapeutic targets that are present in this specific cell type.