ePoster

Effects of progressive dopamine loss on movement cessation and initiation: Insights into basal ganglia network dynamics from a genetic model of Parkinson’s disease

Selena Gonzalez, Ziyang Xiao, Scott Kooiman, Li Yuan, Li Yao, Byung Kook Lim, Jill Leutgeb, Stefan Leutgeb
FENS Forum 2024(2024)
Messe Wien Exhibition & Congress Center, Vienna, Austria

Conference

FENS Forum 2024

Messe Wien Exhibition & Congress Center, Vienna, Austria

Resources

Authors & Affiliations

Selena Gonzalez, Ziyang Xiao, Scott Kooiman, Li Yuan, Li Yao, Byung Kook Lim, Jill Leutgeb, Stefan Leutgeb

Abstract

Understanding the basal ganglia's role in initiating and executing action sequences is crucial for treating Parkinson's disease (PD). Recent experimental data challenge the classical model attributing pro- and anti-kinetic functions to direct and indirect pathways of the basal ganglia. To better understand movement-related neuronal activity in the basal ganglia, we performed large-scale electrophysiological recordings with Neuropixels probes in awake, behaving mice in the dorsomedial and dorsolateral striatum (DMS and DLS, respectively). We used the MitoPark mouse, a genetic model of PD, to investigate precisely-timed neuronal activity patterns during movement sequences and their changes with progressive dopamine neuron loss. We trained control and MitoPark mice in a virtual reality task that required cue-guided stopping and then initiation of running. Despite a minor decrease of striatal dopaminergic fibers in 8-week-old MitoPark mice, there were no differences to controls in cue-guided movement cessation and initiation at this stage. Analysis of the firing of single DMS and DLS cells revealed responses to movement, licking and/or reward. By extending the recordings to older MitoPark mice, characterized by significant dopamine depletion, we anticipate disruptions in movement-related and reward-related firing patterns within the DMS, associated with early visuomotor learning, and the DLS, responsible for sensorimotor function. Our study aims to advance our understanding of basal ganglia function, specifically by clarifying dopamine’s role in striatal firing patterns and by identifying compensatory neuronal activity during the gradual loss of dopamine. These insights could pave the way for discovering novel treatment strategies during progressive loss of dopamine in PD.

Unique ID: fens-24/effects-progressive-dopamine-loss-movement-4deefa52