A postnatal molecular switch drives activity-dependent maturation of parvalbumin interneurons

<p dir="ltr">Cortical neurons are specified during embryonic development but often acquire their mature properties at relatively late stages of postnatal development. This delay in terminal differentiation is particularly prominent for fast-spiking parvalbumin-expressing (PV⁺) interneurons, which play critical roles in regulating the function of the cerebral cortex. We found that the maturation of PV⁺ interneurons is triggered by neuronal activity and mediated by the transcriptional cofactor PGC-1a. Developmental loss of PGC-1a prevents PV⁺ interneurons from acquiring unique structural, electrophysiological, synaptic, and metabolic features and disrupts their diversification into distinct subtypes. PGC-1a functions as a master regulator of the differentiation of PV⁺ interneurons by directly controlling gene expression through a transcriptional complex that includes ERRg and Mef2c transcription factors. Our results uncover a molecular switch that translates neural activity into a specific transcriptional program promoting the maturation of PV⁺ interneurons at the appropriate developmental stage.</p>