Activity of dopaminergic neurons during skilled reaching in head-fixed rats

septembre 2023

Directeur(s) de thèse : Nicolas Mallet

Résumé de thèse

Midbrain dopaminergic neurons (DANs) are essential for associative learning and goal-directed movements. Several studies have recorded their activity during motor tasks and most have observed an increase of dopaminergic activity during movement or around its initiation. However, the functional role played by DANs during instrumental tasks is still unclear. It has been hypothesized that dopamine could modulate movement vigor in an online manner instead of only encoding reward prediction error, but causal experiments have yielded conflicting results. Other theories argue for a role of movement-related dopamine in habit formation or retrospective causal learning, but the extent of dopaminergic contribution to sensory-motor behaviors in physiological conditions is unknown. In this study, we sought to investigate the functional heterogeneity of DANs in the SNc and characterize their activity during a reach-and-grab motor task in TH-Cre rats. We recorded DANs electrical activity and GCamP calcium signal in head-fixed rats performing the operant task using high-density silicon probes and fiber photometry, respectively. We observed that DANs increased their activity, as measured through global calcium signal, both after the auditory cue and during movement execution. Interestingly, the movement-evoked responses were highly lateralized depending on the limb used. We further dissected the neuronal mechanism causing these increases in calcium transients using in vivo electrophysiological recordings. We found that the activity of DANs neurons recorded in the SNc was functionally heterogeneous during the task with individual neurons responding to task events in the specialized-manner. Finally, we observed a correlation between dopaminergic activity and movement vigor, as well as an inhibition of dopaminergic activity during movement repression. Our results reveal the functional diversity present in DANs during a fine operant motor task, and highlight the close relationship between dopamine and motor execution.