The Structure and Function of Ipsilateral Corticospinal Projections

同侧皮质脊髓投射的结构和功能

基本信息

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
项目类别：
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

项目摘要

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.

项目概要大多数皮质脊髓纤维穿过中线形成对侧皮质脊髓束（cCST）。其中约 10% 投射至同侧，形成同侧皮质脊髓束 (iCST)。通过允许未受损的皮质恢复，在单侧中风或其他形式的运动皮质损伤中恢复中发挥作用尽管 iCST 具有临床重要性，但它是自然的。从单侧半球损伤中恢复的个体的功能和详细解剖结构尚不清楚。错误的双侧对称运动被恰当地称为“经颅镜像运动障碍”。磁刺激研究将 iCST 的相对强度与这些镜子的严重程度联系起来此外，具有更强大 iCST 的突变动物表现出双边适应性运动行为这一证据导致了 iCST 参与协调的假设。双边行为。该项目结合了病毒追踪方法、化学遗传学行为实验、单核技术测序和基于测序的神经重建来测试 iCST 协调的假设在初步数据中，开发了一种结合单突触顺行的新策略。追踪和单核测序以绘制 iCST 和 cCST 的突触后靶点图谱。从这种方法中可以看出，两个区域的架构存在自上而下的差异，iCST 预测对于涉及运动控制和 cCST 的中间神经元更是如此，对于那些涉及感觉的神经元更是如此这导致了 iCST 包含双边投射的皮质脊髓神经元的假设。这种分叉的神经元将为 iCST 和双侧运动之间的联系提供结构上的合理性行为：双侧神经元自然处于有利的位置以促进双侧行为，MAPSeq 是一种方法。使用分子条形码的顺行病毒追踪以及双荧光逆行追踪，初步数据表明，除了确保这些之外，iCST 主要由双边投射神经元组成。研究结果是可靠的，该项目将通过使用直接研究 iCST 在运动行为中的作用 iCST 的化学遗传学沉默和完善的行为范式中的无标记姿势估计自适应双边运动。