Investigating Cognitive Control and Search in the Prefrontal-Hippocampal Network

PROJECT SUMMARY/ABSTRACT Multi-step planning is a fundamental basis of human cognition and its impairment in disorders like schizophrenia disrupts goal-directed behavior in everyday situations. Essential to planning is the evaluation of alternative actions based on an internal model of the environment, but the exact neural implementation of this process is poorly understood. Several lines of evidence have implicated the retrosplenial cortex (RSC) in memory, prospection, and action evaluation, which makes the RSC the candidate region where model-based evaluation is most likely performed to support planning. However, the role of RSC in multi-step planning has never directly been tested. This project will address this gap by integrating cellular-resolution calcium imaging and chemogenetic perturbation to monitor and silence the activity of RSC neurons in rats performing a two-step task that elicits planning. By using this strategy, we will directly assess whether the activity of neurons in the RSC (1) encodes the model-based value of future actions and (2) causally contributes to planning behavior during the two-step task - two key evidence that can directly determine RSC’s role in multi-step planning. The identification of neuronal responses supporting multi-step planning will advance our basic understanding of the neurocomputational processes underlying cognition and inform direct translational research on the disruption of flexible behavior among psychiatric patients. The aims of this project resonate with the mission of the BRAIN Initiative in integrating innovative experimental and computational technologies to understand the neural mechanisms of multi-step planning and goal-directed behavior, with potentials for guiding the diagnosis and therapeutic intervention of related psychiatric disorders.