ADOLESCENT MATURATION OF FEEDFORWARD AND FEEDBACK INHIBITORY CIRCUITS IN THE MEDIAL PREFRONTAL CORTEX

During cognitive development, it is crucial that the balance of inhibitory and excitatory neurons within the medial prefrontal cortex (mPFC) is maintained and regulated in forming essential circuits and information loop that enables both feedforward and feedback information flow between the cortex and subcortical regions. Adolescence is a particularly critical period for this refinement, as the mPFC undergoes substantial maturation necessary for executive function, decision-making, and behavioural control.
Previous rabies tracing experiments have shown that NDNF+ and VIP+ interneurons undergo distinct developmental refinement of their cortical and thalamic inputs, contributing to pruning, specificity, and stabilizing connectivity. These patterns suggest differential strategies for organizing inhibitory circuits during adolescence, whereby selective strengthening and elimination of inputs fine-tune the mPFC's characteristics in integrating hierarchical information and implementing appropriate cognitive control.
In layer 5 of the mPFC, it is established that pyramidal tract (PT) cells serve as a primary output hub to various subcortical areas, receiving inputs from layer 2/3 interneurons (feedforward: NDNF+ and VIP+) as well as from within-layer 5 interneurons (feedback: CCK+ and SOM+). Using monosynaptic rabies tracing of pyramidal tract (PT) cells in layer 5 of mPFC, this study aims to map the whole-brain inputs onto L5 PT cells, thereby understanding how these inhibitory microcircuits are organized across different thalamic and subcortical regions, and how their developmental refinement during adolescence influences mPFC output circuits.