Simona Agata Maria Bucolo

Locomotion is a universal behavior that enables animals to explore and interact with their environment. It arises from specialized circuits that plan, command, and execute movement. In Parkinson’s disease (PD), degeneration of nigrostriatal dopamine neurons impairs the function of these circuits with a primary affection of the basal ganglia (BG) with devastating consequences on everyday life due to difficulties in initiating movement.  

Although it is known that brainstem locomotor circuits links action planning to spinal motor execution, the mechanisms by which basal ganglia output engages these circuits to relay motor commands to the spinal cord remain unclear. This proposal will delineate the BG-brainstem pathway responsible for movement initiation and evaluate its therapeutic leverage in PD.  

We will use viral tracing and activity recordings using genetically encoded indicators to define the pathway organization and function at movement onset. Finally, we will assess whether selective recruitment of these neurons restores locomotion in a validated PD mouse model. By coupling specific circuit identification to clinically relevant interventions, this proposal aims to deliver targets for promoting movement initiation in PD.

‍