Elucidating the logic of proprioceptive networks

阐明本体感受网络的逻辑

• 批准号: 10343682
• 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/10343682
• 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： 我们使用精确且受控的运动控制模型与世界互动。 纳入这样的想法：身体必须有其内部状态的表示才能生成所需的 轨迹（前馈）或与已完成的轨迹（反馈）进行比较。 内部状态是利用本体感觉（肢体和身体位置的感觉）产生的，但效果并不好 了解这种感觉是如何产生的，或者其他感觉输入（例如皮肤（触摸）信息）是如何产生的 初级本体感觉神经元的丧失会导致严重的运动障碍。 缺陷，表明本体感觉对于运动功能至关重要，以及皮肤感觉丧失的研究 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，至少有一些本体感觉和皮肤感觉的整合 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的“本体感受”和“外感受”（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作出反应 然而，当时很难区分不同的刺激。 目前的分子谱系追踪技术现在能够区分小鼠的 DSCT 神经元子集。 DSCT 的不同分子子集之间。 该提案的目标是了解本体感觉和皮肤信息是如何组织的 我们在脊髓中的 DSCT 神经元水平上与 DSCT 的离散分子子集进行了斗争。 具有独特的微电路连接性，这对于它们产生本体感觉的功能很重要，我们 将通过以下目标检验这一假设 目标 1 将研究分子和 使用 mRNA 转录本深度测序技术研究 DSCT 神经元的电生理多样性 目标 2 将测试急性脊髓切片中不同子集和特定神经子集的记录。 DSCT 的不同子集是否使用逆行接收皮肤和/或本体感觉信息 目标 3 将检查突触病毒追踪技术是否存在不同的空间轴突轨迹。 DSCT 神经子集进入小脑，以使用整体了解其终止的空间逻辑 总而言之，该提案使用了分子、解剖和电生理学技术。 这项研究将为我们的长期研究奠定基础。 术语目标是理解身体的内部模型是如何构建的。 这项研究的成果将影响体感、运动控制和机器人领域，并提供 深入了解脊髓损伤或神经退行性疾病时需要再生哪些类型的神经回路 疾病状态，例如弗里德里希共济失调。

项目成果

An Atoh1 CRE Knock-In Mouse Labels Motor Neurons Involved in Fine Motor Control.

Atoh1 CRE 敲入小鼠标记参与精细运动控制的运动神经元。

• 发表时间: 2021-01
• 影响因子: 3.4
• 作者: Ogujiofor, Osita W;Pop, Iliodora V;Espinosa, Felipe;Durodoye, Razaq O;Viacheslavov, Michael L;Jarvis, Rachel;Landy, Mark A;Gurumurthy, Channabasavaiah B;Lai, Helen C
• 通讯作者: Lai, Helen C

Nociceptor subtypes are born continuously over DRG development.

伤害感受器亚型在 DRG 发育过程中不断产生。

• 发表时间: 2021-11
• 影响因子: 2.7
• 作者: Landy, Mark A;Goyal, Megan;Lai, Helen C
• 通讯作者: Lai, Helen C

PRDM12 Is Required for Initiation of the Nociceptive Neuron Lineage during Neurogenesis.

PRDM12 是神经发生过程中伤害性神经元谱系启动所必需的。

• 发表时间: 2019
• 影响因子: 8.8
• 作者: Bartesaghi, Luca;Wang, Yiqiao;Fontanet, Paula;Wanderoy, Simone;Berger, Finja;Wu, Haohao;Akkuratova, Natalia;Bouçanova, Filipa;Médard, Jean;Petitpré, Charles;Landy, Mark A;Zhang, Ming;Harrer, Philip;Stendel, Claudia;Stucka, Rolf
• 通讯作者: Stucka, Rolf

Single cell RNA sequencing identifies early diversity of sensory neurons forming via bi-potential intermediates.

单细胞 RNA 测序可识别通过双电位中间体形成的感觉神经元的早期多样性。

• 发表时间: 2020-08-21
• 影响因子: 16.6
• 作者: Faure, Louis;Wang, Yiqiao;Kastriti, Maria Eleni;Fontanet, Paula;Cheung, Kylie K Y;Petitpré, Charles;Wu, Haohao;Sun, Lynn Linyu;Runge, Karen;Croci, Laura;Landy, Mark A;Lai, Helen C;Consalez, Gian Giacomo;de Chevigny, Antoine;Lallemend, Franço
• 通讯作者: Lallemend, Franço