Inhibitory Circuits Underlying Long-range Sensorimotor Integration

描述(申请人提供)：在啮齿动物的触觉系统中，感觉处理是高度活跃的，涉及桶状皮质和触觉运动皮质之间的主动交流。在活体任务依赖的甩动行为中，GABA能中间神经元更为活跃。中间神经元在主动触摸过程中的激活是稀疏编码的原因。TC输入对中间神经元，特别是第4层快速刺激性细胞的募集，在体外和体内都得到了很好的证明。然而，到目前为止，还没有关于感觉皮质内远程M1输入的同等测量结果。因此，我们对大脑皮层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，其中包含特定抑制性神经元和远程突触水平的详细信息，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，我们将系统地比较表达S1中间神经元的5-HT3R、PV和SST中M1 S1投射的性质。在目标2中，我们将系统地比较表达M1中间神经元的5-HT3R、PV和SST中S1 M1投射的性质。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(数字和概率)之间是否存在任何关联。该提案将揭示运动皮质中感觉加工和感觉运动整合的抑制性上下文运动调制潜在的网络机制。这将使我们能够更好地了解成年神经元兴奋-抑制平衡的性质，以及感觉和运动处理的远程调节背后的细胞机制。这项研究的成功完成将提供对运动到感觉投射的路径、层和细胞类型特定性质的全面了解，反之亦然。这项提议可能会产生新的数据和假说，用于理解感觉和运动回路以及感觉-运动整合的神经障碍。大脑皮质神经元的异常电路连接是癫痫、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.