A postnatal molecular switch drives the activity-dependent maturation of parvalbumin interneurons
A postnatal molecular switch drives the activity-dependent maturation of parvalbumin interneurons
Cortical neurons are specified during embryonic development but often only 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 peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α). Developmental loss of PGC-1α prevents PV+ interneurons from acquiring unique structural, electrophysiological, synaptic, and metabolic features and disrupts their diversification into distinct subtypes. PGC-1α exerts its function as a master regulator of the differentiation of PV+ interneurons by directly controlling gene expression through a transcriptional complex that includes ERRγ and Mef2c. 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.
Mar¨an Oscar、Bernard Cl¨|mence、Dom¨anguez Yaiza、Qin Shenyue、Hamid Fursham、Oozeer Fazal、M¨°dol Laura、Kelly Audrey、Abbasova Leyla、Moissidis Monika、Lavender Paul、Alis Rafael、Flames Nuria
Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King?ˉs College London||Medical Research Council Centre for Neurodevelopmental Disorders, King?ˉs College LondonCentre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King?ˉs College London||Medical Research Council Centre for Neurodevelopmental Disorders, King?ˉs College LondonDevelopmental Neurobiology Unit, Instituto de Biomedicina de Valencia IBV-CSICCentre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King?ˉs College London||Medical Research Council Centre for Neurodevelopmental Disorders, King?ˉs College LondonCentre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King?ˉs College London||Medical Research Council Centre for Neurodevelopmental Disorders, King?ˉs College LondonCentre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King?ˉs College London||Medical Research Council Centre for Neurodevelopmental Disorders, King?ˉs College LondonCentre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King?ˉs College London||Medical Research Council Centre for Neurodevelopmental Disorders, King?ˉs College LondonPeter Gorer Department of Immunobiology, School of Immunology and Microbial Science, King?ˉs College London||King?ˉs Centre for Lung Health, King?ˉs College LondonCentre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King?ˉs College London||Medical Research Council Centre for Neurodevelopmental Disorders, King?ˉs College LondonCentre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King?ˉs College London||Medical Research Council Centre for Neurodevelopmental Disorders, King?ˉs College LondonPeter Gorer Department of Immunobiology, School of Immunology and Microbial Science, King?ˉs College London||King?ˉs Centre for Lung Health, King?ˉs College LondonDevelopmental Neurobiology Unit, Instituto de Biomedicina de Valencia IBV-CSICDevelopmental Neurobiology Unit, Instituto de Biomedicina de Valencia IBV-CSIC
分子生物学生理学细胞生物学
Mar¨an Oscar,Bernard Cl¨|mence,Dom¨anguez Yaiza,Qin Shenyue,Hamid Fursham,Oozeer Fazal,M¨°dol Laura,Kelly Audrey,Abbasova Leyla,Moissidis Monika,Lavender Paul,Alis Rafael,Flames Nuria.A postnatal molecular switch drives the activity-dependent maturation of parvalbumin interneurons[EB/OL].(2025-03-28)[2025-06-03].https://www.biorxiv.org/content/10.1101/2024.04.08.588555.点此复制
评论