The Structure and Function of Ipsilateral Corticospinal Projections

同侧皮质脊髓投射的结构和功能

• 批准号: 10678301
• 负责人: Benjamin Fait
• 金额: $ 4.77万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10678301
• 关键词: Address; Anatomy; Animals; Architecture; Atlases; Axon; Bar Codes; Behavior; Behavioral Genetics; Behavioral Paradigm; Bilateral; Biological Assay; Catalogs; Cell Nucleus; Clinical; Clinical Trials; Compensation; Contralateral; Corticospinal Tracts; Data; Data Analyses; Data Set; Development; Ensure; Fiber; Fluorescence; Genetic; Individual; Injury; Interneurons; Ipsilateral; Lead; Learning; Limb structure; Link; Maps; Methods; Molecular; Motor; Motor Cortex; Movement; Movement Disorders; Multiplexed Analysis of Projections by Sequencing; Mus; Mutant Strains Mice; Neuroanatomy; Neurons; Neurosciences; Pattern; Performance; Play; Population; Positioning Attribute; Process; Recovery; Rehabilitation therapy; Research; Resolution; Rodent; Role; Sensory; Severities; Side; Spinal; Spinal Cord; Stroke; Structure; System; Testing; Tissues; Transcranial magnetic stimulation; Vertebral column; Viral; Work; cell type; examination questions; experience; experimental study; genetic manipulation; hemisphere damage; improved; motor behavior; motor control; motor recovery; mutant; neural circuit; nonhuman primate; novel; novel strategies; postsynaptic; reconstruction; rehabilitation strategy; skills; tool; transcriptomics

PROJECT SUMMARY Most corticospinal fibers cross the midline to form the contralateral corticospinal tract (cCST). However, approximately 10% of them project ipsilaterally to form the ipsilateral corticospinal tract (iCST). The iCST plays a role in recovery from unilateral stroke or other forms of motor cortical injury by allowing the undamaged cortical hemisphere to compensate for the damaged one. Despite the clinical importance of the iCST, its naturalistic function and detailed anatomy are unknown. Individuals recovering from unilateral hemispheric injury experience erroneous bilateral and symmetrical movements aptly termed “mirror movement disorders.” Transcranial magnetic stimulation studies have linked the relative strength of the iCST and the severity of these mirror movements. Furthermore, mutant animals with more robust iCSTs perform bilateral adaptive motor behaviors more than wild-type animals. This evidence led to the hypothesis that the iCST is involved in the coordination of bilateral behaviors. This project uses a combination of viral tracing methods, chemogenetic behavioral experiments, single nucleus sequencing, and sequencing-based neuronal reconstruction to test the hypothesis that the iCST coordinates bilateral behavior. In preliminary data, a novel strategy is developed combining monosynaptic anterograde tracing and single nucleus sequencing to map the postsynaptic targets of the iCST and cCST. Preliminary results from this method suggested top-down differences in the architecture of the two tracts, with the iCST projecting more so to interneurons involved in motor control and the cCST more so toward those involved in sensory modulation. This lead to the hypothesis that the iCST comprises bilaterally-projecting corticospinal neurons. Such bifurcated neurons would provide a structural justification for the link between the iCST and bilateral motor behavior: bilateral neurons are naturally well-situated to facilitate bilateral behavior. With MAPSeq, a method of anterograde viral tracing using molecular barcodes, as well as dual-fluorescence retrograde tracing, preliminary data indicated that the iCST comprises primarily of bilaterally-projecting neurons. In addition to ensuring these findings are robust, this project will directly investigate the role of the iCST in motor behavior by using chemogenetic silencing of the iCST and markerless pose estimation in a well-established behavioral paradigm of adaptive bilateral movement.

项目摘要 大多数皮质脊髓纤维穿过中线，形成对比皮质脊髓束（CCST）。然而， 它们中约有10％的同侧投影以形成同侧皮质脊髓束（ICST）。 ICST播放 通过允许不龄皮层从单侧中风或其他形式的运动皮质损伤中恢复中的作用 半球以补偿受损的半球。尽管ICST的临床重要性，但其自然主义 功能和详细的解剖结构尚不清楚。从单侧半球损伤经历中恢复的个人 错误的双边和对称运动被恰当地称为“镜像运动障碍”。经颅 磁模拟研究已将ICST的相对强度和这些镜子的严重程度联系起来 动作。此外，具有更健壮的ICST的突变动物执行双边自适应运动行为 不仅仅是野生型动物。这一证据导致了以下假设：ICST参与了 双边行为。 该项目结合了病毒追踪方法，化学发生行为实验，单核 测序和基于测序的神经元重建，以检验ICST坐标的假设 双边行为。在初步数据中，开发了一种新型策略，结合了单突触的顺行？ 跟踪和单核测序以绘制ICST和CCST的突触后靶标。初步结果 通过这种方法，建议在这两个区域的体系结构上有自上而下的差异，ICST投影 更重要 调制。这导致了这样的假设，即ICST包含双侧注射皮层神经元。 这种分叉的神经元将为ICST和双侧电动机之间的联系提供结构上的理由 行为：双侧神经元自然良好，以促进双边行为。使用MapSeq，一种方法 使用分子条形码以及双荧光逆行痕迹，初步的逆转录曲线，先进的病毒追踪 数据表明，ICST包括双侧预测神经元的一级。除了确保这些 调查结果很健壮，该项目将通过使用直接调查ICST在运动行为中的作用 ICST和无标记姿势估计的化学生成沉默 自适应双侧运动。