Dynamic properties of neural circuits in the forebrain

项目摘要 几乎所有的感觉信号都是通过丘脑进入新皮层的，而感觉皮层又依次分配给大脑。 将此信息传递到几个下游皮质和皮质下区域。一个突出但常被忽视的特征 是来自其他皮层区域的大量反馈投射。这一关键的组织特征 这意味着其他皮层区域正在进行的活动可能会影响局部信息处理 和感觉皮层的输出。事实上，人们认为皮质皮质的交流 注意力、预测、期望和意识等过程。大脑皮层之间的通讯问题 区域也与某些神经精神疾病有关，包括癫痫、自闭症和精神分裂症。 尽管其明显的重要性，彻底了解皮层反馈活动如何影响感官， 处理是难以捉摸的。这项研究的中心目标是确定长距离皮层 反馈投射在细胞、突触和回路水平上影响皮层感觉加工 机制等我们使用小鼠感觉运动系统，一个领先的模型，在三个具体的目标， 用于研究前脑回路和主动感觉。目标1将集中在运动皮层之间的连接 和躯体感觉皮层的2/3层。使用特定的Cre表达小鼠品系和光遗传学，我们将 测试运动反馈参与两个平行但动态不同的抑制系统的假设， 躯体感觉皮层的2/3层。目标2将集中在颗粒层，其中含有混合 兴奋性投射神经元的群体。使用分离的和完整的大脑标本，我们将测试 运动皮层活动引起的兴奋和抑制的动态平衡的假设是显着的 不同的深层投射神经元取决于他们的皮质和皮质下的投射目标。目的 3将使用光遗传学来解开介导第5/6层运动整合的抑制电路， 躯体感觉皮层这个项目将提供急需的洞察皮层反馈系统如何 影响感官处理。这些信息对于理解神经精神疾病是必不可少的 包括反馈交流。

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.