MAPPING VARIABILITY IN CONTEXTUAL REPRESENTATIONS IN THE PREFRONTAL CORTEX DURING GOAL-ORIENTED LEARNING

The medial prefrontal cortex (mPFC) is a key brain area that enables high-order cognitive functions as well as behavioral flexibility by integrating information from various brain regions to guide behavior based on prior experience. Cognitive flexibility depends on the individuals’ capability to memorize previous experiences and to update behavioral strategies in relation to current demands. However, how population activity dynamics in the mPFC relate to context-related task changes remains unclear. Here, we examine what contextual information is represented by prefrontal principal cell assemblies in mice performing a goal-oriented learning (GOL) task during context-dependent rule changes. Using 2-Photon calcium imaging, we recorded neuronal population activity in the mPFC of mice performing a spatial and a non-spatial GOL task in virtual realities during daily task performance for subsequent weeks. We observed marked inter-individual and context-related differences in the speed of goal learning and maximal performance levels. Inter-individual variability in task learning appeared context-dependent. In the spatial task, in which a fixed goal location had to be memorized, a larger fraction of spatially tuned principal cells emerged representing the entire track with their enrichment at goal locations. In contrast, in the non-spatial task in which mice needed to focus on a randomly applied tone to obtain a reward after proactive licking, tone-tuned principal cells predicting the expected reward site dominated, whereas spatially tuned cells appeared more sparsely. Thus, our data suggest that the nature of the task and its complexity play a key role in shaping prefrontal population activity representing the task space.