Dissecting Spinal Interneuron Circuits to Control Skilled Movements

解剖脊髓中间神经元回路来控制熟练的运动

• 批准号: 10583550
• 负责人: Yutaka Yoshida
• 金额: $ 56.35万
• 依托单位: WINIFRED MASTERSON BURKE MED RES INST
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10583550
• 关键词: 11 year old; Address; Affect; Anatomy; Axon; Behavior; Brain; Child; Complex; Cre driver; Data; Development; Disease; Electromyography; Exhibits; Food; Forelimb; Goals; Human; Individual; Injury; Interneuron function; Interneurons; Interruption; Intervention; Knowledge; Lesion; Limb structure; Mammals; Maps; Mediating; Molecular; Motor; Motor Cortex; Motor Neurons; Motor Skills; Movement; Mus; Muscle; Neurons; Pattern; Phase; Primates; Rabies virus; Research; Rodent; Role; SLC17A8 gene; Shapes; Signal Transduction; Spinal; Spinal Cord; Spinal cord injury; Spinal cord posterior horn; Stroke; Synapses; Time; Vertebral column; Virus; designer receptors exclusively activated by designer drugs; disability; expectation; grasp; motor behavior; motor disorder; novel; novel therapeutics; optogenetics; patch clamp; presynaptic; sensory cortex; skills; therapy design

The highly orchestrated muscle activation sequences during motor behaviors are achieved directly through the fine-tuned firing of motor neurons in the ventral spinal cord. These motor neurons are mainly regulated by spinal interneurons present in all mammals, which are, in turn, connected to other spinal neurons as well as various types of descending neurons from the brain, such as corticospinal (CS), reticulospinal and rubrospinal neurons. Until recently, the identities and functioning of the interneuron subtypes and descending neurons participating in individual circuits had remained elusive. What remains lacking is knowledge of the arrangement and functional role of the spinal interneuron subtypes in individual circuits. There is, therefore, a critical need to determine the anatomical and functional connectivity of these spinal interneuron subtypes and how they regulate motor behaviors. Our overall objectives in this application are to (i) map anatomical and functional connectivity of different classes of spinal interneurons (Aims 1 & 2), and (ii) elucidate how those interneurons effect motor behaviors (Aim 3). Our central hypothesis is that each interneuron subtype will exhibit preferential connections with distinct descending neurons to control discrete forms of locomotor and skilled movements.

运动行为期间高度协调的肌肉激活序列直接通过 腹侧脊髓中运动神经元的微调放电。这些运动神经元主要受脊髓神经元的调节。 存在于所有哺乳动物中的中间神经元，其反过来连接到其他脊髓神经元以及各种神经元。 来自脑的下行神经元的类型，如皮质脊髓（CS）、网状脊髓和红核脊髓神经元。 直到最近，中间神经元亚型和下行神经元参与的身份和功能， 个别电路仍然难以捉摸。仍然缺乏的是对安排和功能的了解。 脊髓中间神经元亚型在个体回路中的作用。因此，迫切需要确定 这些脊髓中间神经元亚型的解剖和功能连接以及它们如何调节运动 行为。我们在本申请中的总体目标是（i）映射解剖和功能连接， 不同类别的脊髓中间神经元（目的1和2），以及（ii）阐明这些中间神经元如何影响运动 行为（目标3）。我们的中心假设是，每个中间神经元亚型将表现出优先连接 具有不同的下行神经元来控制离散形式的运动和熟练的动作。