NON-LINEAR CIRCUIT REWIRING IN THE MOUSE PREFRONTAL CORTEX SHAPES THE MATURATION OF WORKING MEMORY ABILITIES

Cognitive flexibility allows individuals to continuously adapt and modify their strategies in response to changing environmental conditions. Within the spectrum of cognitive flexibility, working memory (WM) plays a central role. While multiple brain regions contribute and interact in the execution of WM, the prefrontal cortex (PFC) is widely recognized as a key hub. Mature WM abilities typically emerge towards adult age, coinciding with the non-linear structural and functional reorganization of the PFC. However, little is known about how the maturing PFC facilitates the development of adult-like WM capacities. Here, we investigated mouse WM abilities across different developmental stages - pre-juvenile (postnatal day (P) 20-25), early adolescent (P30-35), late adolescent (P40-45), and adult (P55-60) - using a delayed non-match to sample task. Simultaneously, we recorded local field potentials and single-unit activity from the medial PFC or the hippocampus (HP). We identified two distinct developmental dynamics. First, despite adult-like task performance at pre-juvenile age, recordings from the PFC revealed minimal task-dependent functional recruitment and outcome encoding. In contrast, pre-juvenile hippocampal activity conveyed task-related information comparable to that observed in the adult PFC, suggesting a developmental shift in the brain regions supporting WM computations. Second, we observed a transient decline in WM performance during late adolescence, which was associated with reduced theta-band dynamics and a surge in circulating sex hormone levels. Together, these findings provide novel insights into how age-dependent circuit dynamics within the PFC and HP shape the developmental trajectory of working memory abilities.