Elucidating the logic of proprioceptive networks

阐明本体感受网络的逻辑

• 批准号: 10083234
• 负责人: Helen Lai
• 金额: $ 35.44万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10083234
• 关键词: 3-Dimensional; Ablation; Acute; Anatomy; Animal Model; Animals; Area; Ataxia; Axon; Biology; Categories; Cell Separation; Cells; Cerebellum; Coffee; Complex; Cutaneous; Data; Defect; Dorsal; Electrophysiology (science); Esthesia; Feedback; Felis catus; Foundations; Future; Genetic; Goals; Heterogeneity; Hindlimb; Human; Imaging technology; Individual; Ipsilateral; Knowledge; Lateral; Limb structure; Logic; Maps; Medial; Messenger RNA; Modeling; Molecular; Molecular Probes; Motor; Motor output; Movement; Mus; Muscle; Natural regeneration; Neurodegenerative Disorders; Neurons; Pathway interactions; Peripheral Nervous System Diseases; Phantom Limb; Physiological; Process; Proprioception; Proprioceptor; Research Personnel; Robotics; Role; Signal Transduction; Slice; Spinal Cord; Spinal cord injury; Spinocerebellar Tracts; Stimulus; Techniques; Technology; Tennis; Testing; Texture; Thoracic spinal cord structure; Time; Tissue imaging; Touch sensation; Transcript; Traumatic injury; Viral; Work; base; body map; body position; cell type; cutaneous sensory nerve; cutaneous sensory neurons; deep sequencing; dorsal horn; grasp; insight; mimicry; molecular subtypes; motor behavior; motor control; motor recovery; neural circuit; neurodevelopment; neuronal cell body; neuronal circuitry; patch clamp; progenitor; recruit; sensory input; somatosensory; transcriptome

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.

项目摘要/摘要： 我们使用精确和可控的动作与我们的世界互动。电机控制模型 结合身体必须具有其内部状态的表示的思想，以生成所需的 轨迹(前馈)或与完整轨迹(反馈)进行比较。这张人体地图显示了 内部状态是通过本体感觉、肢体感觉和身体位置产生的，但它并不是很好 了解这种感觉是如何产生的，或者皮肤(触摸)信息等其他感觉输入是如何产生的 向本体感官进食。初级本体感觉神经元丢失导致严重运动 缺陷，表明本体感觉对运动功能是必不可少的，以及对皮肤丧失的研究 感觉神经输入表明，复杂的运动行为需要触觉信息。 对猫的早期研究表明，至少有一部分本体感觉和皮肤的整合 信息发生在脊髓的小脑投射神经元(脊髓小脑神经元)的水平上。 这些研究描述了背部的“本体感觉”和“外部感觉”(皮肤/触觉)细分。 脊髓小脑束(DSCT)，该束内的神经元亚群对本体感觉或 本体感觉和皮肤刺激。然而，在当时，很难区分不同的 DSCT神经元的亚群。目前小鼠的分子谱系追踪技术现在能够区分 在DSCT的不同分子亚集之间。 这项建议的目标是了解本体感觉和皮肤信息是如何组织的 在脊髓DSCT神经元的水平上。我们假设DSCT的离散分子子集 具有独特的微电路连通性，对于它们在产生本体感觉方面的功能很重要，我们 我将通过以下目标来检验这一假设。目标1将研究分子和 应用mRNA转录本深度测序技术研究DSCT神经元的电生理多样性 急性脊髓切片的不同亚群和特定神经元亚群的记录。AIM 2将测试 DSCT的不同子集是否使用逆行接收皮肤和/或本体感觉信息 跨突触病毒追踪技术。目标3将检查是否存在不同的空间轴突轨迹 DSCT神经元亚群进入小脑以了解其终末的空间逻辑 组织成像技术。总之，这项提议使用了分子、解剖学和电生理学 阐明DSCT神经元连通性的方法。这项研究将为我们长期的- 术语目标是了解身体的内部模型是如何构建的。基础知识 这项研究将对躯体感觉、运动控制和机器人领域产生影响，并提供 关于脊髓损伤或神经退行性变后需要再生哪种神经回路的见解 疾病状态，如弗里德里希共济失调。