Role of histone deacetylases in the development of GABAergic interneuron connectivity and function

组蛋白脱乙酰酶在 GABA 能中间神经元连接和功能发育中的作用

• 批准号: RGPIN-2016-06067
• 负责人: DiCristo, Graziella
• 金额: $ 3.21万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629250
• 关键词: Role; histone; deacetylases; development; GABAergic

GABAergic neurons form an important subset of the neuronal population in the brain, which powerfully control the dynamics of brain circuits. In addition, they strongly regulate brain development by modulating several processes including experience-dependent neuronal wiring. The complexity of brain circuitry and the non-homogeneity of the GABAergic cell population has so far made the study of how these neurons develop and form synaptic connections very difficult. We have recently developed techniques to label and manipulate parvalbumin positive GABAergic cells (PV cells), which constitute the most numerous types of cortical GABAergic neurons. PV cells form dense axonal arborisations that innervate hundreds of target neurons, each with multiple, clustered synapses onto their soma and proximal dendrites. Such precise subcellular location of PV cell synapses, in conjunction with their striking ability to fire sustained trains of brief action potentials at remarkably high frequency, allows them to powerfully control the output of their target cells and influence large network activities in the brain. My long-term goal is to understand the mechanisms underlying the formation of cortical PV cell connectivity and how they modulate experience-dependent cortical plasticity in the young and adult brain.

GABA能神经元是脑内神经元的重要组成部分，对脑回路的动力学起着重要的控制作用。此外，它们通过调节几个过程，包括经验依赖性神经元布线，强烈调节大脑发育。大脑回路的复杂性和GABA能细胞群的非同质性使得迄今为止对这些神经元如何发育和形成突触连接的研究非常困难。我们最近开发了标记和操纵小清蛋白阳性GABA能细胞（PV细胞）的技术，PV细胞构成了最多类型的皮质GABA能神经元。PV细胞形成密集的轴突分支，支配数百个靶神经元，每个靶神经元在其索马和近端树突上具有多个成簇的突触。PV细胞突触的这种精确的亚细胞定位，结合它们以非常高的频率发射持续的短暂动作电位序列的惊人能力，使它们能够有力地控制其靶细胞的输出并影响大脑中的大型网络活动。我的长期目标是了解皮层PV细胞连接形成的机制，以及它们如何调节年轻和成年大脑中依赖于经验的皮层可塑性。