NEUROPHYSIOLOGICAL DEVELOPMENT OF LAYER 3 PYRAMIDAL AND PARVALBUMIN NEURONS IN THE MOUSE PREFRONTAL CORTEX ACROSS ADOLESCENCE

Normal development of the medial prefrontal cortex (mPFC) is critical for higher-order cognitive processes, and dysfunction in this region is implicated in numerous developmental and neuropsychiatric disorders. Although the micro- and macro-circuitry of the mPFC are well characterised, comparatively little is known about the cellular-level maturation of mPFC neurons across the adolescent sensitive period.
To address this gap, we performed whole-cell patch-clamp recordings from layer 3 pyramidal (PYR) neurons and fast-spiking parvalbumin-expressing (PV+) interneurons in the prelimbic cortex at three developmental stages: pre-adolescence (P25), adolescence (P40), and early adulthood (P55) in mice. We assessed both intrinsic electrophysiological properties and spontaneous postsynaptic activity in both cell types.
Previous studies in lower-order cortices have described physiological maturation of PYR and PV+ neurons during sensitive periods, and prior work from our group identified a peak in synaptic maturation during adolescence. Consistent with this, we observed significant age-dependent changes in multiple intrinsic and synaptic parameters, providing insight into the cellular mechanisms underlying higher-order cortical development. Ongoing work will extend these analyses to deeper cortical layers and examine the maturation of thalamocortical inputs - particularly onto layer 3 - offering a framework for understanding typical adolescent development, and how it may be disrupted.