Inhibitory Circuits Underlying Long-range Sensorimotor Integration

描述（由申请人提供）：在啮齿动物的振动系统中，感觉加工是高度活跃的，涉及到桶状皮层和振动运动皮层之间的主动交流。在体内任务依赖的瞬变行为中，gaba能中间神经元更加活跃。在主动触摸过程中，中间神经元的激活负责稀疏编码。中间神经元的募集，特别是第4层快速尖峰细胞通过TC输入，已经在体外和体内得到了很好的记录。然而，对于感觉皮层内的远程M1输入，还没有相应的测量报告。因此，我们对皮质计算的关键组成部分缺乏了解。我们的首要目标是构建一个详细的电路图，在特定的抑制性神经元和远程突触的水平上提供详细的信息，以帮助理解S1和M1内互惠感觉运动关联的电路基础。在Aim 1中，我们将系统地比较M1 在5-HT3R、PV和SST表达S1中间神经元中的S1投射。在Aim 2中，我们将系统地比较S1 M1在5-HT3R、PV和SST表达M1中间神经元中的投射。目的3将补充目的1和2，并检查突触强度（映射数据，目的1和2）和放电（数字和概率）之间是否存在任何相关性。该建议将揭示在运动皮层抑制情境运动调制的感觉加工和感觉运动整合的网络机制。这将使我们更好地了解成人神经元兴奋-抑制平衡的本质，以及感觉和运动加工远程调节的细胞机制。这项研究的成功完成将提供对运动到感觉投射的通路、层和细胞类型特异性的全面理解，反之亦然。这一建议可能会产生新的数据和假设，以理解感觉和运动电路和神经系统疾病的感觉-运动整合。皮层神经元的异常电路连接是社交和认知功能障碍（如癫痫、自闭症和精神分裂症）的关键特征。因此，揭示皮层神经元间回路的组织也将有助于为未来解剖特定的神经元类型、突触和由精神疾病改变的回路奠定基础。

DESCRIPTION (provided by applicant): In the rodent vibrissal system, sensory processing is highly active and involves active communication between the barrel cortex and the vibrissal motor cortex. During task-dependent whisking behavior in vivo, GABAergic interneurons are more active. The activation of interneurons during active touch is responsible for sparse coding. Recruitment of interneurons, particularly layer 4 fast-spiking cells by TC inputs, has been well documented both in vitro and in vivo. However, no equivalent measurements have yet been reported for long-range M1 inputs within the sensory cortex. We therefore lack understanding of critical components of cortical computation. Our overarching goal is to construct a detailed circuit diagram, with detailed information at the level of specific inhibitory neurons and long-range synapses, to help understand the circuit basis underlying reciprocal sensorimotor associations within the S1 and M1. In Aim 1, we will systematically compare properties M1  S1 projections in 5-HT3R, PV and SST expressing S1 interneurons. In Aim 2, we will systematically compare properties S1 M1 projections in 5-HT3R, PV and SST expressing M1 interneurons. Aim 3 will supplement Aims 1& 2 and examine if there are any correlation between synaptic strength (mapping data, Aim 1& 2) and firing (numbers and probabilities). The proposal will uncover network mechanisms underlying inhibitory contextual motor modulation of sensory processing and sensorimotor integration at motor cortex. This will allow us to gain better understanding about the nature of the excitation-inhibition balance in adult neurons and cellular mechanisms underlying long-range modulation of sensory and motor processing. Successful completion of this study will provide a comprehensive understanding of pathway, layer and cell-type specific nature of motor to sensory projections, and vice versa. This proposal will likely generate novel data and hypotheses for understanding sensory and motor circuit and neurological disorders with sensory-motor integration. Abnormal circuit wiring in cortical neurons is the key features of social and cognitive dysfunction such as epilepsy, autism and schizophrenia. Therefore, unveiling the cortical interneuronal circuit organization will also help o build the groundwork for future dissection of specific interneuronal types, synapses and circuits altered by mental diseases.