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

GABA能神经元是大脑中神经元群体的一个重要子集，它有力地控制着大脑回路的动力学。到目前为止，大脑回路的复杂性和GABA能细胞群的非均质性使得研究这些神经元如何发育和形成突触连接变得非常困难。我们最近开发了标记和操作小白蛋白阳性GABA能细胞(PV细胞)的技术，这些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树枝状分支，支配数百个靶神经元，每个神经元在其胞体和近端树突上有多个簇状突触。光伏细胞突触的这种精确的亚细胞定位，加上它们以极高的频率发射持续的短暂动作电位序列的打击能力，使它们能够有力地控制目标细胞的输出，并影响大脑中的大型网络活动。特别是，光伏细胞的活动可以调节个体如何感知和解释来自其环境的感觉信息(感官知觉)。我的长期目标是了解皮质光伏细胞形成和功能的潜在机制，以及光伏细胞如何反过来调节大脑功能。哺乳动物的感官知觉受性腺激素的调节。例如，在女性的月经周期中，感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细胞的活动，进而调节感官知觉，目前尚不清楚。这个问题将是这个研究项目的重点。这项研究的结果将阐明性别和激素依赖的感官知觉差异背后的细胞机制。拟议方法的多学科核心将为总部基地人员在研究生和本科生层面提供极好的培训机会。

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.