Motor feedback control of layer six circuits

项目摘要 新皮层对于运动、感觉和高级认知功能至关重要。一个关键的组织特征 是它包括几个不同的区域，这些区域通过长距离皮质皮层相互连接， 途径。这些直接的皮质连接通常被认为是介导认知过程， 注意力、预测和意识。皮质连接功能障碍与某些 神经系统疾病，如自闭症、癫痫和精神分裂症。长距离皮质连接 等级组织的皮层区域。例如，低级皮层区域，如感觉皮层 通过前馈通路（FF）将感觉感受野信息传递到高阶区域。在 相反，高阶皮层区域向低阶区域发送反馈投射（FB），并被认为是 调节其靶细胞的反应性。最近的研究表明，局部GABA能中间神经元发挥作用， 在皮层反馈调制中起着关键作用。虽然我们对FB募集抑制因子的作用已经有了很多了解， 浅层（第2/3层）中的回路，深层中涉及FB调制的潜在抑制回路 （第5/6层）未知。事实上，以前的解剖学和生理学研究强烈表明，IN 群体在皮层的表层和深层之间是不同的，这表明不同的抑制性 大脑皮层的反馈回路也可能参与其中。本论文将研究抑制性网络 介导的小鼠体感皮层第6层中的运动整合。其中有三个具体目标 建议：1）表征由vM 1输入招募的第6层抑制性细胞类型; 2）确定 L 6兴奋性细胞的亚型被vM 1输入激活; 3）确定vM 1诱发的FFI的功能， L 6的兴奋细胞。为了实现这些目标，我将使用一系列体外电生理技术， 结合各种光遗传学方法、转基因小鼠品系和组织学方法来鉴定 在躯体感觉皮层的L 6中调节运动整合的抑制回路。最终，这些发现 将推进我们对皮质连接的基本理解，以及运动皮质如何影响 在感觉皮层中进行处理。这些信息对于理解某些神经精神疾病是必要的。 涉及皮质皮质通讯的疾病。

PROJECT SUMMARY The neocortex is essential for movement, sensation, and higher cognitive functions. A key organization feature of the cortex is that it comprises several distinct areas that are interconnected by long-range corticocortical pathways. These direct corticocortical connections are generally thought to mediate cognitive processes like attention, prediction, and awareness. Dysfunction in corticocortical connectivity has been associated with certain neurological disorders like autism, epilepsy, and schizophrenia. Long-range corticocortical connections link hierarchically organized cortical areas. For example, lower-order cortical areas such as sensory cortices communicate sensory receptive field information to higher-order areas via feedforward pathways (FF). In contrast, higher-order cortical areas send feedback projections (FB) to lower-order areas and are thought to modulate the responsiveness of their target cells. Recent work suggests that local GABAergic interneurons play a critical role in cortical feedback modulation. Although much is known about the FB recruitment of inhibitory circuits in superficial layers (layer 2/3), the underlying inhibitory circuits involved in FB modulation in deep layers (layer 5/6) are unknown. Indeed, previous anatomical and physiological studies strongly suggest that IN populations are distinct between superficial and deep layers of the cortex, suggesting that different inhibitory circuits could be involved in cortical feedback circuits. This proposal will investigate the inhibitory networks mediated motor integration in layer 6 of the mouse somatosensory cortex. There are three specific aims in this proposal: 1) Characterize layer 6 inhibitory cell types recruited by vM1 input; 2) Determine what different subtypes of L6 excitatory cells are activated by vM1 input; 3) Determine the functions of vM1 evoked FFI to excitatory cells in L6. To address these aims, I will use an array of in vitro electrophysiological techniques combined with various optogenetics approaches, transgenic mouse lines, and histological methods to identify the inhibitory circuits mediating motor integration in L6 of the somatosensory cortex. Ultimately, these findings will advance our fundamental understanding of corticocortical connectivity and how the motor cortex influences processing in the sensory cortex. Such information will be necessary for understanding certain neuropsychiatric disorders involving corticocortical communication.