Sex- and hormone-dependent recruitment of inhibitory neurons in rodent sensory cortex

啮齿动物感觉皮层抑制性神经元的性别和激素依赖性募集

• 批准号: RGPIN-2022-04444
• 负责人: DiCristo, Graziella
• 金额: $ 2.48万
• 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: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=761464
• 关键词: Sex; hormone; dependent; recruitment; inhibitory

GABAergic neurons form an important subset of the neuronal population in the brain, which powerfully control the dynamics of brain circuits. 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. In particular, PV cell activity can modulate how an individual perceives and interprets the sensory information coming from their environment (sensory perception). My long-term goal is to understand the mechanisms underlying the formation and function of cortical PV cells and how, in turn, PV cells regulate brain functions. Sensory perception is modulated by gonadal hormones in mammals. For example, sensory perception is altered in subtle ways during the menstrual cycle in women. Whether and how gonadal hormones regulate PV cell activity, and in turn, sensory perception, is unclear. This question will be the focus of this research program. The results of this research will shed light on the cellular mechanisms underlying sex- and hormones-dependent differences in sensory perception. The multidisciplinary core of the proposed approaches will provide excellent training opportunities for HQPs at both the graduate and undergraduate levels.

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。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与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相结合，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。特别是，PV细胞活动可以调节个体如何感知和解释来自其环境的感官信息（感官感知）。我的长期目标是了解皮层PV细胞形成和功能的机制，以及PV细胞如何调节大脑功能。 哺乳动物的感觉知觉受性腺激素的调节。例如，在女性月经周期中，感官知觉会以微妙的方式发生变化。性腺激素是否以及如何调节PV细胞活性，进而调节感觉知觉，目前尚不清楚。这个问题将是本研究计划的重点。这项研究的结果将阐明细胞机制的性别和性别依赖性差异的感官知觉。拟议方法的多学科核心将为研究生和本科生层次的HQP提供极好的培训机会。