The Structure and Function of Ipsilateral Corticospinal Projections

项目摘要 大多数皮质脊髓纤维穿过中线形成对侧皮质脊髓束（cCST）。然而，在这方面， 其中约10%向同侧突出形成同侧皮质脊髓束（iCST）。iCST播放 在单侧中风或其他形式的运动皮层损伤中的恢复作用， 以弥补受损的半球。尽管iCST的临床重要性，其自然 功能和详细解剖结构未知。从单侧半球损伤中恢复的个体经历 错误的双侧和对称运动，恰当地称为“镜像运动障碍”。经颅 磁刺激研究已经将iCST的相对强度与这些镜像的严重程度联系起来， 动作此外，具有更强iCST的突变动物执行双侧适应性运动行为 超过野生动物。这一证据导致了iCST参与协调 双边行为。 本项目采用病毒示踪方法、化学发生行为学实验、单核 测序和基于测序的神经元重建，以检验iCST协调 双边行为。在初步数据中，开发了一种新的策略， 示踪和单核测序以绘制iCST和cCST的突触后靶点。初步结果 从这种方法中可以看出，两个神经束的结构存在自上而下的差异，iCST投影 对参与运动控制的中间神经元更是如此，而cCST对参与感觉控制的中间神经元更是如此。 调变这导致iCST包括双侧投射的皮质脊髓神经元的假设。 这种分叉的神经元将为iCST和双侧运动神经元之间的联系提供结构上的合理性。 行为：双侧神经元自然地处于良好位置以促进双侧行为。使用MAPSeq， 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，iCST主要包括双侧投射神经元。除了确保这些 研究结果是强大的，这个项目将直接调查的作用，iCST在运动行为，通过使用 iCST的化学遗传学沉默和在完善的行为范例中的无标记姿势估计 适应性双侧运动。

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.