Elucidating the logic of proprioceptive networks

项目概要/摘要： 我们使用精确和受控的运动与我们的世界互动。运动控制模型 结合身体必须有其内部状态的表示来生成所需的 轨迹（前馈）或与完成的轨迹（反馈）进行比较。这张人体地图 内部状态是使用本体感觉，肢体和身体位置的感觉产生的，但它并不好 理解这种感觉是如何产生的，或者其他感觉输入，如皮肤（触摸）信息， 进入本体感觉初级本体感觉神经元的丧失导致严重的运动神经元损伤。 缺陷，表明本体感觉是必不可少的运动功能，和研究的损失，皮肤 感觉神经输入表明复杂的运动行为需要触摸信息。 早期对猫的研究表明，至少有一些本体感受和皮肤的整合， 信息发生在脊髓中小脑投射神经元（脊髓小脑神经元）的水平。 这些研究描述了背侧皮层的"本体感受性"和"外感受性"（皮肤/触觉）细分， 脊髓小脑束（DSCT），其中该束内的神经元子集响应本体感受或 本体感受和皮肤刺激。然而，在当时，很难区分不同的 DSCT神经元的子集。目前的小鼠分子谱系追踪技术现在能够区分 不同分子亚型之间的差异 本提案的目标是了解本体感受和皮肤信息是如何组织的 在脊髓中的DSCT神经元水平。我们假设DSCT的离散分子亚群 具有独特的微电路连接，对于它们产生本体感觉的功能很重要， 我们将通过以下目标来检验这一假设。目的1将研究分子和 使用mRNA转录物的深度测序技术的DSCT神经元的电生理多样性 不同的子集和记录特定的神经元亚群在急性脊髓切片。目标2将测试 DSCT的不同亚组是否使用逆行接收皮肤和/或本体感受信息 跨突触病毒追踪技术。目标3将检查是否有不同的空间轴突轨迹， DSCT神经元亚群进入小脑，以了解其终止的空间逻辑， 组织成像技术。总而言之，这项建议使用分子，解剖学和电生理学 方法来阐明DSCT神经元的连接。这项研究将成为我们长期的基础- 理解身体内部模型是如何构建的长期目标。基础知识 从这项研究中获得的信息将影响躯体感觉、运动控制和机器人技术领域， 了解什么样的神经回路需要在脊髓损伤或神经变性后再生 疾病状态，如弗里德里希共济失调。

Project Summary/Abstract: We interact with our world using precise and controlled movements. Models of motor control incorporate the idea that the body must have a representation of its internal state to generate either a desired trajectory (feedforward) or to compare with for the completed trajectory (feedback). This body map of the internal state is produced using proprioception, the sense of limb and body position, yet it is not well understood how this sense is generated or how other sensory inputs such as cutaneous (touch) information feed into the proprioceptive sense. Loss of primary proprioceptive sensory neurons leads to severe motor defects, indicating that proprioception is essential for motor function, and studies of the loss of cutaneous sensory nerve inputs shows that touch information is needed for complex motor behaviors. Early studies in cats suggest that at least some of the integration of proprioceptive and cutaneous information happens at the level of cerebellar-projecting neurons in the spinal cord (spinocerebellar neurons). These studies describe “proprioceptive” and “exteroceptive” (cutaneous/touch) subdivisions of the dorsal spinocerebellar tract (DSCT) whereby subsets of neurons within this tract respond to either proprioceptive or proprioceptive and cutaneous stimulation. However, at the time, it was difficult to differentiate between different subsets of DSCT neurons. Current molecular lineage tracing technologies in mice are now able to differentiate between different molecular subsets of the DSCT. The goal of this proposal is to understand how proprioceptive and cutaneous information is organized at the level of DSCT neurons in the spinal cord. We hypothesize that discrete molecular subsets of the DSCT have distinct microcircuit connectivity important for their function in generating the proprioceptive sense and we will test this hypothesis through the following Aims. Aim 1 will investigate the molecular and electrophysiological diversity of DSCT neurons using deep sequencing technologies for the mRNA transcripts of different subsets and recordings of specific neuronal subsets in acute spinal cord slices. Aim 2 will test whether different subsets of the DSCT receive cutaneous and/or proprioceptive information using retrograde transsynaptic viral tracing techniques. Aim 3 will examine if there are different spatial axonal trajectories of DSCT neuronal subsets into the cerebellum to understand the spatial logic of their terminations using whole tissue imaging technologies. Altogether, this proposal uses molecular, anatomical, and electrophysiological approaches to elucidate the connectivity of DSCT neurons. This study will form the foundation for our long- term goal of understanding how internal models of the body are constructed. The fundamental knowledge gained from this study will impact the fields of somatosensation, motor control, and robotics as well as provide insights into what kinds of neural circuits need to be regenerated upon spinal cord injury or neurodegenerative disease states, such as Friedrich's ataxia.