Functions of naturally diverse inhibitory networks in neocortex

描述（由申请人提供）：抑制性神经元在新皮层的正常信息处理中起关键作用。此外，它们的功能障碍可能有助于某些疾病的病理生理基础。迄今为止，我们对抑制性神经元及其突触的各种功能的了解大多是通过对感觉皮层的研究揭示出来的。我的长期目标是确定局部抑制网络的巨大区域差异是否会导致新皮层中不同的抑制和网络机制。我的工作将特别集中在内侧前额叶皮层（mPFC）和腹侧鼻后皮层（vPOR），与感觉皮层相比，表达小白蛋白（PV）的中间神经元非常少的大脑区域。PFC和POR分别对认知控制和视觉空间注意至关重要，它们缺乏PV-中间神经元可能在这些区域如何正常处理信息中起关键作用。本提案有三个具体目标：1)表征和比较mPFC和vPOR内的局部抑制网络；2)探讨丘脑皮质前馈抑制在mPFC和vPOR中的细胞机制；3)确定mPFC和vPOR中伽马振荡的细胞机制。我所有的数据将与我从初级体感皮层（SI）获得的数据进行比较，SI是研究新皮层回路结构和生理学的领先模型。为了实现这些目标，我将结合使用体外膜片钳技术、各种光遗传学方法、定量组织学方法和多种转基因小鼠系来识别、选择和操纵特定神经元的活动。我的研究将阐明新皮层中神经回路的基本生理学和多样性。它还可能阐明某些抑制能力受损的神经精神疾病。

DESCRIPTION (provided by applicant): Inhibitory neurons play a critical role in normal information processing in the neocortex. Moreover, their dysfunction may contribute to the pathophysiology underlying certain disorders. To date, most of our understanding of the diverse functions of inhibitory neurons and their synapses has been revealed through studies of sensory cortices. My long range goal is to determine if dramatic regional differences in local inhibitory networks result in distinct inhibitory and network mechanisms in the neocortex. My work will specifically focus on the medial prefrontal cortex (mPFC) and ventral postrhinal cortex (vPOR), brain areas with remarkably few parvalbumin- (PV) expressing interneurons compared to sensory cortices. The PFC and POR are essential in cognitive control and visuospatial attention, respectively, and their lack of PV- interneurons could play a pivotal role in how these areas normally process information. There are three specific aims in this proposal: 1) To characterize and compare the local inhibitory networks within the mPFC and vPOR; 2) To dissect the cellular mechanisms underlying thalamocortical feedforward inhibition in the mPFC and vPOR ; 3) To determine the cellular mechanisms underlying gamma oscillations in the mPFC and vPOR. All my data will be compared to data I obtain from the primary somatosensory cortex (SI), a leading model for studying the structure and physiology of neocortical circuits. To address these aims I will use a combination of in vitro patch clamp techniques, various optogenetic approaches, quantitative histological methods, and multiple transgenic lines of mice to identify, select, and manipulate activity of specific neurons. My research will illuminate the basic physiology and diversity of neural circuits in the neocortex. It also may shed light on certain neuropsychiatric conditions in which inhibition is compromised.