Dynamic properties of neural circuits in the forebrain

前脑神经回路的动态特性

• 批准号: 10443280
• 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/10443280
• 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; Ursidae Family; autism spectrum disorder; base; burden of illness; cognitive process; expectation; in vivo; information processing; inhibitory neuron; insight; motor behavior; motor control; neglect; nervous system disorder; neural circuit; 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.

项目摘要 几乎所有的感觉信号通过丘脑进入新皮层，而感觉皮层则又分发 这些信息给了几个下游皮层和皮层下区域。突出但经常被忽视的功能 感官皮层的含量是来自其他皮质区域的大量反馈预测。这个关键的组织特征 大脑暗示其他皮质区域正在进行的活动可能会影响当地信息处理 以及感觉皮层的输出。实际上，皮质皮质交流被认为可以介导认知 注意力，预测，期望和意识等过程。皮质之间的沟通问题 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。 尽管其重要性很明显，但对皮质反馈活动如何影响感官有深入的了解 处理一直难以捉摸。这项调查的核心目标是确定皮质的距离 反馈预测会影响细胞，突触和电路水平的皮质感觉处理 机制。我们使用鼠标感官系统（一个领先的模型 用于研究前脑电路和主动感觉。 AIM 1将重点放在电动机皮层之间的连接上 和体感皮质的第2/3层。使用表达特定Cre的小鼠系和光遗传学，我们将 测试以下假设，即电机反馈与两个相似但动态不同的抑制系统参与 体感皮质的第2/3层。 AIM 2将重点放在含层的层，其中包含混合 兴奋性投影神经元的种群。使用孤立和完整的大脑制剂，我们将测试 假设运动皮层活性引起的激发和抑制的动态平衡是巨大的 在深层投影神经元中不同，具体取决于其皮质和皮层投射靶标。目的 3将使用光遗传学来阐明介导运动整合的抑制电路 体感皮质。该项目将提供急需的洞察力，了解皮质反馈系统如何 影响感官处理。这些信息对于理解神经精神疾病至关重要 涉及反馈沟通。