Department of Neuroscience, UT Southwestern Medical Center, Dallas, Texas 75390.
Mathematical Biosciences Institute, Ohio State University, Columbus, Ohio 43210.
J Neurosci. 2022 Jan 26;42(4):581-600. doi: 10.1523/JNEUROSCI.2157-20.2021. Epub 2021 Dec 2.
Proprioception, the sense of limb and body position, generates a map of the body that is essential for proper motor control, yet we know little about precisely how neurons in proprioceptive pathways are wired. Defining the anatomy of secondary neurons in the spinal cord that integrate and relay proprioceptive and potentially cutaneous information from the periphery to the cerebellum is fundamental to understanding how proprioceptive circuits function. Here, we define the unique anatomic trajectories of long-range direct and indirect spinocerebellar pathways as well as local intersegmental spinal circuits using genetic tools in both male and female mice. We find that Clarke's column neurons, a major contributor to the direct spinocerebellar pathway, has mossy fiber terminals that diversify extensively in the cerebellar cortex with axons terminating bilaterally, but with no significant axon collaterals within the spinal cord, medulla, or cerebellar nuclei. By contrast, we find that two of the indirect pathways, the spino-lateral reticular nucleus and spino-olivary pathways, are in part, derived from cervical -lineage neurons, whereas thoracolumbar -lineage neurons project mostly locally within the spinal cord. Notably, while cervical and thoracolumbar -lineage neurons connect locally with motor neurons, no Clarke's column to motor neuron connections were detected. Together, we define anatomic differences between long-range direct, indirect, and local proprioceptive subcircuits that likely mediate different components of proprioceptive-motor behaviors. We define the anatomy of long-range direct and indirect spinocerebellar pathways as well as local spinal proprioceptive circuits. We observe that mossy fiber axon terminals of Clarke's column neurons diversify proprioceptive information across granule cells in multiple lobules on both ipsilateral and contralateral sides, sending no significant collaterals within the spinal cord, medulla, or cerebellar nuclei. Strikingly, we find that cervical spinal cord -lineage neurons form mainly the indirect spino-lateral reticular nucleus and spino-olivary tracts and thoracolumbar -lineage neurons project locally within the spinal cord, whereas only a few -lineage neurons form a direct spinocerebellar tract.
本体感觉，即肢体和身体位置的感觉，生成了一个身体地图，对于正确的运动控制至关重要，但我们对本体感觉通路中的神经元是如何连接的知之甚少。定义整合来自外周的本体感觉和潜在皮肤感觉信息并将其中继到小脑的脊髓中次级神经元的解剖结构，是理解本体感觉回路如何发挥功能的基础。在这里，我们使用雄性和雌性小鼠中的遗传工具定义了长程直接和间接脊髓小脑途径以及局部节段间脊髓回路的独特解剖轨迹。我们发现，Clarke 柱神经元是直接脊髓小脑途径的主要贡献者，其苔藓纤维终末在小脑皮质中广泛多样化，轴突双侧终止，但在脊髓、延髓或小脑核内没有明显的轴突侧支。相比之下，我们发现间接途径中的两个，即脊髓-侧网状核和脊髓-橄榄核途径，部分来源于颈系神经元，而胸腰系神经元主要在脊髓内局部投射。值得注意的是，虽然颈系和胸腰系神经元与运动神经元局部连接，但未检测到 Clarke 柱到运动神经元的连接。总之，我们定义了长程直接、间接和局部本体感觉亚回路之间的解剖差异，这些差异可能介导了本体感觉-运动行为的不同成分。我们定义了长程直接和间接脊髓小脑途径以及局部脊髓本体感觉回路的解剖结构。我们观察到，Clarke 柱神经元的苔藓纤维轴突终末在同侧和对侧的多个小叶中的颗粒细胞中多样化本体感觉信息，在脊髓、延髓或小脑核内没有明显的侧支。引人注目的是，我们发现颈脊髓系神经元主要形成间接的脊髓-侧网状核和脊髓-橄榄核束，而胸腰脊髓系神经元在脊髓内局部投射，而只有少数神经元形成直接的脊髓小脑束。
