Sensing active movement of the self: reconsidering the cellular basis kinesthesia

感知自我的主动运动：重新考虑细胞基础运动感觉

• 批准号: 10618908
• 负责人: Paul D. Marasco
• 金额: $ 55.2万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-06 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10618908
• 关键词: Ablation; Adult; Amputation; Amputees; Area; Bionics; Brain; Calcium; Caliber; Characteristics; Classification; Clinical; Code; Complex; Disease; Electrophysiology (science); Environment; Esthesia; Evaluation; Exhibits; Feedback; Focal Dystonias; Foundations; Frequencies; Genetic; Golgi Tendon Organs; Histologic; Human; Image; Immunologics; Individual; Infrastructure; Interoception; Intervention; Intramuscular; Kinesthesis; Kinesthetic Illusions; Knowledge; Learning; Link; Liquid substance; Mediating; Modeling; Molecular; Morphology; Motor; Movement; Mus; Muscle; Muscle Contraction; Muscle Fibers; Muscle Spindles; Nature; Neurons; Outcome; Parkinson Disease; Perception; Peripheral; Peripheral Nervous System Diseases; Population; Property; Proprioceptor; Prosthesis; Publishing; Rattus; Reflex action; Role; Sensory; Sensory Receptors; Skeletal Muscle; Stimulus; Stroke; System; Testing; Translating; Translational Research; Translations; United States National Institutes of Health; Visit; Work; calbindin; clinical application; clinical care; cortex mapping; design; frontier; improved; limb movement; motor control; motor deficit; musculoskeletal injury; neural; neural circuit; novel; preservation; prevent; receptor; response; restoration; sensor; sensory stimulus; stroke model; stroke patient; success; theories; tool; transcriptome; translational medicine; vibration

Abstract The sense of movement (kinesthesia) provides an interoceptive internal readout of our physical actions in space and is essential for our ability to move fluidly and effectively through our environment. Despite kinesthesia's importance in motor function and self-reference, our understanding of this sense is plagued by glaring knowledge gaps and inconsistencies. Movement sensations are traditionally believed to be a specialized function of type Ia muscle spindle afferents. Yet, the apparent disconnect between the peripheral coding properties of this receptor and the sensory stimuli known to evoke a sense of movement have raised questions regarding their primary role in kinesthesia. Although proprioceptive interventions provide functional motor improvements for many conditions such as stroke, Parkinson's disease, focal dystonia, peripheral neuropathies, and musculoskeletal injuries, the lack of a clear scientific foundation for kinesthesia impacts our understanding of sensory-motor deficits and prevents important breakthroughs from translating into clinical successes and targeted intervention strategies. From our recent work we have multiple lines of evidence that suggest there may be sensory muscle receptors, outside of the traditional muscle spindles and Golgi tendon organs that exhibit features consistent with a kinesthetic sensor. First, our peripheral electrophysiological recordings in rat demonstrate a population of fast- conducting rapidly-adapting afferents, that are distinct from muscle spindle and Golgi tendon organ afferents, yet are selectively activated in the frequency bandwidth associated with kinesthetic illusions. Second, our immunological analyses in mouse skeletal muscle reveal a new population of large caliber Calbindin28k+ afferents that do not associate with muscle spindle or Golgi tendon organ receptors but instead terminate in free endings that spread out alongside extrafusal muscle fibers. In a movement-perception study with human neural- machine interface amputees, we found that vibration-induce illusory kinesthetic percepts were linked to muscle contraction not elongation. These results were corroborated in a human stroke model where we amplified kinesthetic perception linked to active muscle contraction which resulted in improved reaching trajectories. With these observations we hypothesize that there are candidate muscle sensory afferents, distinct from type Ia afferents, which selectively respond to muscle fiber contraction. The studies in this proposal will explore the relationships between the response properties and physical characteristics of these candidate kinesthetic receptors and the traditionally defined muscle sensory receptors using genetic, histological, and electrophysiological approaches. Additionally, we will examine this systems functionality with respect to contractile features and its ability to serve as a stimulus for active movement sensing. The discovery and evaluation of the cellular basis of kinesthesia will fundamentally transform our understanding of sensory-motor control and, by extension, will impact design strategies for advanced neural-machine interface prosthetic devices for amputees, as well as other disorders with sensory-motor deficiencies such as stroke.

摘要 运动感(动觉)为我们在太空中的身体动作提供了一种内部感官读数。 对于我们在我们的环境中流畅有效地移动是必不可少的。尽管动觉 运动功能和自我参照的重要性，我们对这一意义的理解被耀眼的知识所困扰 差距和不一致。运动感觉传统上被认为是Ia型的一种特殊功能 肌梭传入。然而，这种受体的外周编码特性之间的明显脱节 已知的能唤起运动感的感官刺激已经对它们的主要作用提出了质疑 在动觉方面。尽管本体感觉干预为许多情况提供了功能性运动改善 如中风、帕金森氏症、局灶性肌张力障碍、周围神经疾病和肌肉骨骼损伤， 缺乏明确的运动感觉科学基础影响了我们对感觉-运动缺陷的理解 防止重要突破转化为临床成功和有针对性的干预策略。 从我们最近的工作中，我们有多条证据表明，可能存在感觉肌肉受体， 除了传统的肌梭和高尔基肌腱器官外，这些器官的特征与 动觉传感器。首先，我们的大鼠外周电生理记录显示了一组快速的- 进行快速适应传入，不同于肌梭和高尔基肌腱器官传入， 但在与动觉错觉相关的频率带宽中被选择性地激活。第二，我们的 小鼠骨骼肌的免疫学分析揭示了一个新的大口径Calbindin28K+群体 与肌梭或高尔基肌腱器官感受器无关但以游离方式终止的传入 沿着梭外肌纤维展开的末端。在一项对人类神经的运动感知研究中- 在机械接口截肢者中，我们发现振动诱导的错觉运动知觉与肌肉有关 收缩而不是伸长。这些结果在人类中风模型中得到了证实，在那里我们放大了 运动知觉与主动肌肉收缩有关，这导致了伸展轨迹的改善。使用 这些观察结果我们假设存在与Ia型不同的候选肌肉感觉神经传入 传入神经，选择性地对肌肉纤维收缩做出反应。 本提案中的研究将探索反应特性与物理特性之间的关系 这些候选运动感觉受体和传统定义的肌肉感觉受体的特征 使用遗传学、组织学和电生理学方法。此外，我们还将检查这些系统 关于收缩特征的功能，以及它作为主动运动感觉的刺激的能力。 动觉细胞基础的发现和评价将从根本上改变我们的理解。 感觉-运动控制，进而将影响先进的神经-机器接口的设计策略 截肢者的假肢装置，以及其他有感觉运动障碍的疾病，如中风。