Venue: Centre Broca
Aryn Gittis
Department of Biological sciences
Carnegie Mellon University, Pittsburgh USA
https://www.cmu.edu/bio/people/faculty/gittis.html
Title
Circuit Inspired Strategies to Improve Treatments for Parkinson’s disease
Abstract
Dopamine loss alters the activity of neural circuits in the basal ganglia, contributing to motor symptoms of Parkinson’s disease and catalepsy. Treatments that reduce basal ganglia output alleviate motor symptoms but require constant maintenance. Cell-type specific interventions provide longer-lasting benefits, but a poor understanding of the therapeutic pathways involved limits translation. Here we identify a neural pathway that converges in the medial SNr whose activation restores flexible behavior and counteracts parkinsonian pathophysiology for a prolonged period in dopamine depleted mice. To probe the mechanisms underlying this response, we used an artificial neural network to identify signatures of electrophysiological dysfunction in the SNr and establish the features that most accurately predict long lasting therapeutic effects. Together, these findings define a neural circuit substrate for promoting sustained behavioral recovery and network plasticity under dopamine depleted conditions, providing a conceptual framework for repairing, rather than masking, network dysfunction in disease.