Inhibitory Circuits Underlying Long-range Sensorimotor Integration

描述（由申请人提供）：在啮齿动物触须系统中，感觉处理高度活跃，涉及桶皮质和触须运动皮质之间的主动通信。在体内任务依赖性搅拌行为中，GABA能中间神经元更活跃。主动触摸期间中间神经元的激活负责稀疏编码。招募的中间神经元，特别是第4层的快速尖峰细胞的TC输入，已在体外和体内有很好的记录。然而，还没有相当的测量报告的长距离M1输入内的感觉皮层。因此，我们对皮质计算的关键组成部分缺乏了解。我们的总体目标是构建一个详细的电路图，在特定的抑制性神经元和长程突触的水平上提供详细的信息，以帮助理解S1和M1内相互感觉运动关联的电路基础。在目标1中，我们将系统地比较性质M1  5-HT 3R、PV和SST表达S1中间神经元中的S1投射。在目标2中，我们将系统地比较性质S1 表达M1中间神经元的5-HT 3R、PV和SST中的M1投射。目标3将补充目标1和2，并检查突触强度（映射数据，目标1和2）和放电（数量和概率）之间是否存在任何相关性。本研究旨在揭示运动皮层感觉加工和感觉运动整合的抑制性情境运动调制的网络机制。这将使我们能够更好地了解成年神经元中兴奋-抑制平衡的性质以及感觉和运动处理的长程调制的细胞机制。本研究的成功完成将提供一个全面的了解途径，层和细胞类型的特定性质的运动到感觉的投射，反之亦然。这一提议可能会产生新的数据和假设，以了解感觉和运动回路和神经系统疾病与感觉运动整合。皮层神经元中的异常电路布线是癫痫、自闭症和精神分裂症等社会和认知功能障碍的关键特征。因此，揭示皮层神经元间回路组织也将有助于为未来解剖特定的神经元间类型，突触和神经回路改变精神疾病奠定基础。

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.