A postnatal molecular switch drives activity-dependent maturation of parvalbumin interneurons.
Por:
Moissidis M, Abbasova L, Selten M, Alis R, Bernard C, Domínguez-Canterla Y, Oozeer F, Qin S, Kelly A, Mòdol L, Vasistha NA, Jones B, Dhami P, Khodosevich K, Hamid F, Lavender P, Flames N and Marín O
Publicada:
2 oct 2025
Ahead of Print:
1 oct 2025
Resumen:
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 peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (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 ERR? 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.
Filiaciones:
Moissidis M:
Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE1 1UL, UK
Medical Research Council Centre for Neurodevelopmental Disorders, King's College London, London SE1 1UL, UK
Abbasova L:
Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE1 1UL, UK
Medical Research Council Centre for Neurodevelopmental Disorders, King's College London, London SE1 1UL, UK
Selten M:
Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE1 1UL, UK
Medical Research Council Centre for Neurodevelopmental Disorders, King's College London, London SE1 1UL, UK
Alis R:
Developmental Neurobiology Unit, Instituto de Biomedicina de Valencia IBV-CSIC, Valencia 46012, Spain
Valencia Biomedical Research Foundation, Centro de Investigación Príncipe Felipe (CIPF), Associated Unit to the Instituto de Biomedicina de Valencia (IBV), Valencia 46012, Spain
Bernard C:
Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE1 1UL, UK
Medical Research Council Centre for Neurodevelopmental Disorders, King's College London, London SE1 1UL, UK
:
Developmental Neurobiology Unit, Instituto de Biomedicina de Valencia IBV-CSIC, Valencia 46012, Spain
Valencia Biomedical Research Foundation, Centro de Investigación Príncipe Felipe (CIPF), Associated Unit to the Instituto de Biomedicina de Valencia (IBV), Valencia 46012, Spain
Oozeer F:
Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE1 1UL, UK
Medical Research Council Centre for Neurodevelopmental Disorders, King's College London, London SE1 1UL, UK
Qin S:
Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE1 1UL, UK
Medical Research Council Centre for Neurodevelopmental Disorders, King's College London, London SE1 1UL, UK
Kelly A:
Peter Gorer Department of Immunobiology, School of Immunology and Microbial Science, King's College London, London SE1 9RT, UK
King's Centre for Lung Health, King's College London, London SE1 9RT, UK
Mòdol L:
Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE1 1UL, UK
Medical Research Council Centre for Neurodevelopmental Disorders, King's College London, London SE1 1UL, UK
Vasistha NA:
Biotech Research and Innovation Center (BRIC), Copenhagen Biocenter, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark
Jones B:
Genomics Research Platform and Single Cell Laboratory, Guy's Hospital, London SE1 9RT, UK
Dhami P:
Genomics Research Platform and Single Cell Laboratory, Guy's Hospital, London SE1 9RT, UK
Khodosevich K:
Biotech Research and Innovation Center (BRIC), Copenhagen Biocenter, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark
Hamid F:
Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE1 1UL, UK
Medical Research Council Centre for Neurodevelopmental Disorders, King's College London, London SE1 1UL, UK
Lavender P:
Peter Gorer Department of Immunobiology, School of Immunology and Microbial Science, King's College London, London SE1 9RT, UK
King's Centre for Lung Health, King's College London, London SE1 9RT, UK
Flames N:
Developmental Neurobiology Unit, Instituto de Biomedicina de Valencia IBV-CSIC, Valencia 46012, Spain
Valencia Biomedical Research Foundation, Centro de Investigación Príncipe Felipe (CIPF), Associated Unit to the Instituto de Biomedicina de Valencia (IBV), Valencia 46012, Spain
Marín O:
Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE1 1UL, UK
Medical Research Council Centre for Neurodevelopmental Disorders, King's College London, London SE1 1UL, UK
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