Motor feedback control of layer six circuits

项目总结 新皮质是运动、感觉和高级认知功能所必需的。一个关键的组织特征 皮质的特点是它由几个不同的区域组成，这些区域通过远程皮质相互连接 小路。这些直接的皮质连接通常被认为调节认知过程，如 注意、预测和觉察。皮质连接功能障碍与某些 神经疾病，如自闭症、癫痫和精神分裂症。远程皮质连接链接 按层次组织的皮质区域。例如，低阶皮质区域，如感觉皮质 通过前馈通路(FF)将感觉接受场信息传递到更高阶区。在……里面 相比之下，高阶皮质区域向低阶区域发送反馈投影(FB)，并被认为 调节他们的目标细胞的反应能力。最近的研究表明，局部GABA能中间神经元在 在大脑皮层反馈调节中起着关键作用。尽管关于FB的抑制性募集已知很多 浅层(层2/3)的电路，深层参与FB调制的潜在抑制电路 (第5/6层)未知。事实上，之前的解剖学和生理学研究有力地表明，在 皮层浅层和深层的种群是不同的，这表明不同的抑制 大脑皮层反馈回路中可能有回路参与。这项提案将研究抑制网络 介导小鼠体感皮质第6层的运动整合。这其中有三个具体目标 建议：1)表征由VM1输入招募的第6层抑制细胞类型；2)确定有什么不同 L6兴奋性细胞亚型由VM1传入激活；3)测定VM1诱发FFI的功能 L6的兴奋性细胞。为了达到这些目标，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 调节躯体感觉皮层L6运动整合的抑制回路。最终，这些发现 将促进我们对皮质连接和运动皮质如何影响的基本理解 在感觉皮层中进行处理。这些信息对于理解某些神经精神病学是必要的。 涉及皮质沟通的障碍。

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.