Basal ganglia output - entopeduncular nucleus - coding of contextual kinematics and reward in the freely moving mouse

The entopeduncular nucleus (EPN) is often termed as one of the output nuclei of the basal ganglia owing to their highly convergent anatomy. The rodent EPN has been implicated in reward and value coding whereas the primate analogue internal Globus Pallidus has been found to be modulated by some movements and in some circumstances. In this study we sought to understand how the rodent EPN might be coding kinematic, reward, and difficulty parameters, particularly during locomotion. Furthermore, we aimed to understand the level of movement representation: whole-body or specific body parts. To this end, mice were trained in a freely moving two-alternative forced choice task with two periods of displacement (return and go trajectories) and performed electrophysiological recordings together with video-based tracking. We found 1) robust reward coding but not difficulty. 2) Spatio-temporal variables better explain EPN activity during movement compared to kinematic variables, while both types of variables were more robustly represented in reward-related movement. 3) Reward sensitive units encode kinematics similarly to reward insensitive ones. 4) Population dynamics that best account for differences between these two periods of movement can be explained by allocentric references like distance to reward port. 5) The representation of paw and licks is not mutually exclusive, discarding a somatotopic muscle-level representation of movement in the EPN. Our data suggest that EPN activity represents movements and reward in a complex way: highly multiplexed, influenced by the objective of the displacement, where trajectories that lead to reward better represent spatial and kinematic variables. Interestingly, there are intertwining representations of whole-body movement kinematics with single paw and licking variables. Further, reward sensitive units encode kinematics similarly to reward insensitive ones, challenging the notion of distinct pathways for reward and movement processing. Significance StatementThe entopeduncular nucleus is one of the main outputs of the basal ganglia whose activity has been hypothesized to be inversely correlated with movement. This study examines motor and reward coding simultaneously, finding that besides the great level of multiplexing of these variables, spatio-temporal coding is better represented than kinematic coding. The level of movement representation seems to be greatly influenced by the goal of a movement, with spatially biased variables influencing the population dynamics of this nucleus. Further, we uncover the coexistence of EPN modulation by movement at different timescales and body parts. The simple overall activity of this output nucleus cannot explain kinematic coding, challenging leading theories of basal ganglia function.