Functions of naturally diverse inhibitory networks in neocortex

新皮质中自然多样化的抑制网络的功能

• 批准号: 8594774
• 负责人: Shane R Crandall
• 金额: $ 4.92万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8594774
• 关键词: Address; Architecture; Area; Arousal; Attention; Autistic Disorder; Brain; Brain region; Calcium-Binding Proteins; Categories; Communication; Data; Disease; Dorsal; Epilepsy; Foundations; Frequencies; Functional disorder; Generations; Goals; Histological Techniques; In Vitro; Interneuron function; Interneurons; Lead; Light; Medial; Mediating; Memory; Mental disorders; Methods; Morphology; Motor; Mus; Mutation; Neocortex; Neurons; Neuropeptides; Parvalbumins; Patch-Clamp Techniques; Pattern; Physiology; Play; Population; Prefrontal Cortex; Process; Property; Proteins; Reaction Time; Relative (related person); Research; Rodent; Role; Schizophrenia; Sensory; Shapes; Somatosensory Cortex; Somatostatin; Structure; Structure-Activity Relationship; Study models; Synapses; Techniques; Testing; Thalamic structure; Transgenic Mice; Transgenic Organisms; Variant; Visuospatial; Work; base; cell type; cognitive control; density; design; excitatory neuron; falls; gamma-Aminobutyric Acid; hippocampal pyramidal neuron; information processing; inhibitory neuron; insight; language perception; neocortical; nervous system disorder; neural circuit; neuropsychiatry; optogenetics; public health relevance; regional difference; research study; response; sensory cortex; serotonin receptor

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.

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导致某些疾病的病理生理学基础。迄今为止，我们对抑制性神经元及其突触的各种功能的理解大多是通过对感觉皮层的研究来揭示的。我的长期目标是确定局部抑制网络的显著区域差异是否会导致新皮层中不同的抑制和网络机制。我的工作将特别关注内侧前额叶皮层（mPFC）和腹后嗅皮层（vPOR），与感觉皮层相比，这些大脑区域具有非常少的小白蛋白（PV）表达中间神经元。PFC和POR分别在认知控制和视觉空间注意中是必不可少的，它们缺乏PV-中间神经元可能在这些区域正常处理信息的方式中发挥关键作用。本研究有三个具体目的：1）表征和比较mPFC和vPOR中的局部抑制网络; 2）剖析mPFC和vPOR中丘脑皮层前馈抑制的细胞机制; 3）确定mPFC和vPOR中γ振荡的细胞机制。我的所有数据将与我从初级躯体感觉皮层（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主要模型。为了实现这些目标，我将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个转基因小鼠系的组合来识别，选择和操纵特定神经元的活性。我的研究将阐明新皮层神经回路的基本生理学和多样性。它也可能揭示某些神经精神疾病，其中抑制是妥协。