StartAct · Controlling forelimb actions through basal ganglia to brainstem signaling

Controlling forelimb actions through basal ganglia to brainstem signaling

Behavior arises from the combination of different movements and is controlled by neuronal circuits distributed throughout the nervous system. Most work in the past focused on high motor centers and executive circuits in the spinal cord, but how these systems are linked to function is poorly understood. The Substantia Nigra Reticulata (SNR), a basal ganglia output involved in action initiation and control, sends projections to many different structures, including the brainstem. However, how the brainstem processes these inputs to control actions remains unknown. The brainstem contains specialized neuronal populations that control specific actions, including skilled forelimb movements and locomotion. Here, we proposed to investigate the impact of SNR signaling on the activity of specific brainstem neurons when a mouse initiates forelimb movements. Understanding the role of SNR input should disclose the fine-scale machinery for initiating and controlling actions. This level of understanding is critical for designing new therapies to help people impaired in self-initiating actions, as in Parkinson’s disease. This project aims to understand the mechanisms by which the basal ganglia output circuits influence brainstem centers in the initiation, execution, and modulation of specific forms of movement. To this end, we planned to characterize and exploit the functional specialization of both the brainstem and the basal ganglia by focusing on the input to the circuit controlling forelimb-reaching movements in the Lateral Rostral Medulla (LatRM). We found that the SNR sends direct GABAergic input to the LatRM region, where it contacts a variety of neuronal subpopulations. Furthermore, we found that these LatRM neurons also receive direct GABAergic input from a region contiguous to the SNR, yet belonging to a different brain-wide circuit. From these results, we conclude that the SNR-to-LatRM circuit can be exploited to gain a mechanistic understanding of the role of basal ganglia in action initiation and control. However, a higher-than-anticipated molecular and functional specificity level is required to restrict the investigative focus to the specific role of the basal ganglia in a single behavioral module. Finally, preliminary high-density recordings from the SNR-to-LatRM neurons in behaving mice began to unravel the dynamic profile of these neurons under physiological conditions. Such dynamics highlighted a possible role of these neurons in shaping the timing of behavior.

Data: CORDIS, © European Union