Browsing by Subject "Basal Ganglia"

The mechanisms by which the nervous system generates action are subjects of ongoing debate. A large body of research supports a role for the striatal direct and indirect pathways in regulating actions. On the one hand, these pathways are critical for discrete decision-making, action initiation, and coordinating sequences of actions. These findings have led to the development of action selection models of striatal circuits. On the other hand, they also play a role in steering motion direction, are related to the kinematics of individual body parts, and coordinated movements. These insights have led to competing hypotheses about their control over bodily kinematics. These divergent hypotheses may have arisen from the functional diversity of subpopulations within striatal neurons. However, prior work supporting these hypotheses of striatal function has not measured both the discrete and continuous features of actions while recording and manipulating striatal pathways. To address this limitation, we designed a novel lever press count task that allows for this combined measurement. Our results show that mice accurately estimate press count and use it to decide when to approach a food port. Optogenetic manipulations reveal that the direct and indirect pathways oppositely control mice’s proximity to task-relevant landmarks and to the press count goal. In-vivo calcium imaging reveals distinct population activities that are correlated with mice’s displacement from task-relevant landmarks and completion of the press count. A striatal push-pull circuit is described that computes the mouse’s proximity to task-relevant landmarks and the press count through subtraction of population activity over time. This work sheds light on a potentially general function of striatal neurons in regulating action during goal pursuit, with implications for understanding action dysregulation in many conditions.