Activity-dependent and molecular mechanisms regulating the development of cortical connectivity

摘要

Roles of striatal direct and indirect pathways in value-based decision making The striatum is critically involved in value-based decision making. However, it is unclear how the striatal direct and indi- rect pathways work together to make optimal choices in a dynamic and uncertain environment. To better understand stri- atal neural processes underlying value-based decision making, we compared discharge patterns and inactivation effects of stri- atal direct-pathway and indirect-pathway neurons using D1-Cre and D2-Cre mice. Direct-pathway neurons tended to increase activity while indirect-pathway neurons decrease activity as a function of reward value during a probabilistic classical condition- ing task, suggesting the striatum represents value in the relative activity levels of direct-pathway versus indirect-pathway neurons. We also found that previous reward-related responses are more frequent among indirect-pathway than direct-pathway striatal neurons, suggesting stronger contributions of indirect-pathway neurons to outcome-dependent behavioral adjustment. Selective chemogenetic inactivation of either direct-pathway or indirect- pathway striatal neurons impaired choice behavior in a dynamic two-armed bandit task. However, the pattern of altered choice behavior differed between the two animal groups. A reinforce- ment learning model-based analysis indicated that inactivation of direct-pathway and indirect-pathway neurons selectively impairs value-dependent action selection and value updating, respectively. Our results indicate differential contributions of the striatal direct and indirect pathways to value representation, value updating and value-based action selection.