Laboratorio de Plasticidad Neuronal, Fundación Instituto Leloir-Instituto de Investigaciones Bioquímicas de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Av. Patricias Argentinas 435, Buenos Aires C1405BWE, Argentina.
Science. 2016 Oct 28;354(6311):459-465. doi: 10.1126/science.aaf2156. Epub 2016 Oct 27.
Experience shapes the development and connectivity of adult-born granule cells (GCs) through mechanisms that are poorly understood. We examined the remodeling of dentate gyrus microcircuits in mice in an enriched environment (EE). Short exposure to EE during early development of new GCs accelerated their functional integration. This effect was mimicked by in vivo chemogenetic activation of a limited population of mature GCs. Slice recordings showed that mature GCs recruit parvalbumin γ-aminobutyric acid-releasing interneurons (PV-INs) that feed back onto developing GCs. Accordingly, chemogenetic stimulation of PV-INs or direct depolarization of developing GCs accelerated GC integration, whereas inactivation of PV-INs prevented the effects of EE. Our results reveal a mechanism for dynamic remodeling in which experience activates dentate networks that "prime" young GCs through a disynaptic feedback loop mediated by PV-INs.
经验通过尚未完全了解的机制塑造成年产生的颗粒细胞 (GCs) 的发育和连接。我们研究了丰富环境 (EE) 中小鼠齿状回微电路的重塑。在新 GCs 的早期发育过程中短暂暴露于 EE 会加速它们的功能整合。体内化学遗传激活有限数量的成熟 GCs 可以模拟这种效果。切片记录显示,成熟 GCs 招募具有反馈作用的囊泡蛋白γ-氨基丁酸释放中间神经元 (PV-INs) 作用于发育中的 GCs。因此,化学遗传刺激 PV-INs 或直接去极化发育中的 GCs 会加速 GCs 的整合,而抑制 PV-INs 会阻止 EE 的作用。我们的研究结果揭示了一种动态重塑的机制,其中经验激活齿状回网络,通过 PV-INs 介导的二突触反馈回路“启动”年轻的 GCs。