Dynamic properties of neural circuits in the forebrain

前脑神经回路的动态特性

• 批准号: 10597109
• 负责人: Shane R Crandall
• 金额: $ 38.42万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10597109
• 关键词: Address; Anatomy; Area; Attention; Awareness; Brain; Cells; Characteristics; Color; Communication; Consensus; Cre driver; Data; Electrophysiology (science); Epilepsy; Equilibrium; Esthesia; Exhibits; Feedback; Feeds; Genetic; Glutamates; Goals; In Vitro; Investigation; Kinetics; Knowledge; Mediating; Motor; Motor Cortex; Mus; Neocortex; Neurons; Optics; Output; Pathway interactions; Pattern; Peripheral; Physiological; Play; Population; Preparation; Property; Prosencephalon; Pyramidal Cells; Role; Schizophrenia; Sensory; Shapes; Signal Transduction; Somatosensory Cortex; Source; Study models; Synapses; Synaptic Transmission; System; Techniques; Testing; Thalamic structure; autism spectrum disorder; burden of illness; cognitive process; expectation; in vivo; information processing; inhibitory neuron; insight; motor behavior; motor control; neglect; neocortical; nervous system disorder; neural circuit; neuronal excitability; neuropsychiatric disorder; optogenetics; recruit; sensorimotor system; sensory cortex; sensory system; tool

PROJECT SUMMARY Nearly all sensory signals enter the neocortex by way of the thalamus, and the sensory cortex, in turn, distributes this information to several downstream cortical and subcortical areas. A prominent but often neglected feature of the sensory cortex is numerous feedback projections from other cortical areas. This key organizational feature of the brain implies that the ongoing activities in other cortical regions may influence local information processing and the outputs of the sensory cortex. Indeed, corticocortical communication is thought to mediate cognitive processes such as attention, prediction, expectation, and awareness. Communication problems between cortical areas are also associated with certain neuropsychiatric disorders, including epilepsy, autism, and schizophrenia. Despite its obvious importance, a thorough understanding of how cortical feedback activity influences sensory processing has been elusive. The central goal of this investigation is to determine how long-range cortical feedback projections influence cortical sensory processing at the level of cellular, synaptic, and circuit mechanisms. We address this goal in three specific aims using the mouse sensorimotor system, a leading model for studying forebrain circuits and active sensation. Aim 1 will focus on the connections between the motor cortex and layer 2/3 of the somatosensory cortex. Using specific Cre-expressing mouse lines and optogenetics, we will test the hypothesis that motor feedback engages two parallel but dynamically distinct systems of inhibition in layer 2/3 of the somatosensory cortex. Aim 2 will focus on infragranular layers, which contained a mixed population of excitatory projection neurons. Using both isolated and intact brain preparations, we will test the hypothesis that the dynamic balance of excitation and inhibition caused by motor cortex activity is dramatically different across deep-layer projection neurons depending on their cortical and subcortical projection target. Aim 3 will use optogenetics to unravel the inhibitory circuits mediating motor integration in layer 5/6 of the somatosensory cortex. This project will provide much-needed insight into how cortical feedback systems influence sensory processing. Such information will be essential for understanding neuropsychiatric disorders involving feedback communication.

项目概要 几乎所有的感觉信号都通过丘脑进入新皮层，感觉皮层依次分配 该信息传递给几个下游皮质和皮质下区域。一个突出但经常被忽视的功能 感觉皮层的大量反馈投射来自其他皮层区域。这一关键的组织特征 大脑的变化意味着其他皮质区域正在进行的活动可能会影响局部信息处理 以及感觉皮层的输出。事实上，皮质沟通被认为可以调节认知 注意力、预测、期望和意识等过程。皮质间的沟通问题 这些区域还与某些神经精神疾病有关，包括癫痫、自闭症和精神分裂症。 尽管其重要性显而易见，但全面了解皮层反馈活动如何影响感觉 处理一直难以捉摸。这项研究的中心目标是确定远程皮质如何 反馈投射影响细胞、突触和电路层面的皮质感觉处理 机制。我们使用小鼠感觉运动系统（一种领先的模型）在三个具体目标中实现这一目标 用于研究前脑回路和主动感觉。目标 1 将重点关注运动皮层之间的连接 和体感皮层的2/3层。使用特定的 Cre 表达小鼠品系和光遗传学，我们将 检验以下假设：运动反馈涉及两个平行但动态不同的抑制系统 体感皮层的2/3层。目标 2 将重点关注粒下层，其中包含混合的 兴奋性投射神经元群。使用分离的和完整的大脑制剂，我们将测试 假设运动皮层活动引起的兴奋和抑制的动态平衡是显着的 深层投射神经元的不同取决于其皮质和皮质下投射目标。目的 3 将利用光遗传学来解开介导大脑 5/6 层运动整合的抑制电路 体感皮层。该项目将为皮层反馈系统如何提供急需的见解 影响感觉加工。这些信息对于理解神经精神疾病至关重要 涉及反馈沟通。