Dynamic properties of neural circuits in the forebrain

项目总结 几乎所有的感觉信号都通过丘脑进入新大脑皮层，而感觉皮质反过来又分布 这一信息传递到几个下游皮质和皮质下区域。一个突出但经常被忽视的特征 感觉皮层是来自其他皮质区域的大量反馈投射。这一关键的组织功能 大脑的活动表明，其他皮质区域正在进行的活动可能会影响局部信息处理 以及感觉皮质的输出。事实上，皮质通讯被认为是调节认知的媒介。 注意、预测、期望和意识等过程。大脑皮层之间的通信问题 这些区域还与某些神经精神障碍有关，包括癫痫、自闭症和精神分裂症。 尽管其重要性显而易见，但对大脑皮层反馈活动如何影响感觉的透彻理解 处理过程一直难以捉摸。这项调查的中心目标是确定多长距离的皮质 反馈投射在细胞、突触和回路水平上影响大脑皮层感觉加工 机械装置。我们使用鼠标感觉运动系统，一个领先的模型，在三个具体目标中实现了这一目标 用于研究前脑回路和主动感觉。目标1将专注于运动皮质之间的联系 和躯体感觉皮质的2/3层。利用特定的表达Cre的小鼠系和光遗传学，我们将 检验运动反馈涉及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将专注于粒下层，其中包含混合的 兴奋性投射神经元的群体。使用分离的和完整的大脑准备，我们将测试 假设由运动皮质活动引起的兴奋和抑制的动态平衡是显著的 深层投射神经元之间的差异取决于它们的皮质和皮质下投射目标。目标 3将使用光遗传学来解开在5/6层中介导运动整合的抑制电路 躯体感觉皮质。该项目将提供对大脑皮层反馈系统如何 影响感官处理。这些信息对于了解神经精神障碍是必不可少的。 涉及反馈沟通。

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.