近日，英国伦敦国王学院教授Oscar Marín小组的研究开发出了出生后的分子开关驱动小白蛋白中间神经元的活动依赖性成熟。2025年7月15日出版的《细胞》杂志发表了这项成果。
课题组发现PV+中间神经元的成熟是由神经元活性触发的，并由转录辅助因子过氧化物酶体增殖体激活受体- γ辅助激活因子1- α (PGC-1α)介导。PGC-1α的发育缺失阻止了PV+中间神经元获得独特的结构、电生理、突触和代谢特征，并破坏了它们向不同亚型的多样化。PGC-1α通过包括ERRγ和Mef2c转录因子在内的转录复合体直接控制基因表达，是PV+中间神经元分化的主要调控因子。他们的研究结果揭示了一个分子开关，将神经活动转化为特定的转录程序，促进PV+中间神经元在适当的发育阶段成熟。
据了解，皮层神经元在胚胎发育期间被指定，但通常在出生后发育的相对较晚阶段获得其成熟特性。这种终末分化的延迟在快速尖峰小蛋白表达（PV+）中间神经元中尤为突出，它们在调节大脑皮层的功能中起着关键作用。
附：英文原文
Title: A postnatal molecular switch drives activity-dependent maturation of parvalbumin interneurons
Author: Monika Moissidis, Leyla Abbasova, Martijn Selten, Rafael Alis, Clémence Bernard, Yaiza Domínguez-Canterla, Fazal Oozeer, Shenyue Qin, Audrey Kelly, Laura Mòdol, Navneet A. Vasistha, Benjamin Jones, Pawan Dhami, Konstantin Khodosevich, Fursham Hamid, Paul Lavender, Nuria Flames, Oscar Marín
Issue&Volume: 2025-07-15
Abstract: 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-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 functions as a master regulator of the differentiation of PV+ interneurons by directly controlling gene expression through a transcriptional complex that includes ERRγ 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.
DOI: 10.1016/j.cell.2025.06.029
Source: https://www.cell.com/cell/abstract/S0092-8674(25)00731-7