Abstract
<jats:p>Higher order association cortices like the prefrontal cortex (PFC) mature over a longer developmental window than sensory cortices, but whether genetically defined interneuron populations follow this region-wide delayed trajectory remains unclear. We compared the postnatal development of somatostatin-expressing interneurons in a higher-order cortical region (prelimbic cortex; PLC) and a sensory cortical region (somatosensory barrel cortex; S1BF) across adolescence using complementary structural, electrophysiological, and circuit analyses. We found that the maturation of SST neurons within these two cortical regions differs across time. S1BF SST neurons exhibited relatively linear maturation, whereas PLC SST neurons underwent continued dendritic remodeling, nonlinear intrinsic maturation, and age-dependent refinement of inhibitory output onto pyramidal neurons. Multivariate analyses likewise supported a more linear developmental trajectory in S1BF and a more prolonged, heterogeneous trajectory in PLC. This suggests divergent maturation of the PLC and S1BF and supports a broader, longer window of critical cellular plasticity in the PLC than in sensory cortices. Together, this reflects an extended developmental program at the level of a genetically defined inhibitory cell type. Because SST neurons are positioned to regulate pyramidal neuron output via control of dendritic integration, their delayed maturation is a crucial reflection of overall circuit function. These findings provide a cellular framework for the prolonged plasticity and developmental vulnerability known to be characteristic of adolescent prelimbic cortex.</jats:p>