Structure of Long-Range Direct and Indirect Spinocerebellar Pathways as Well as Local Spinal Circuits Mediating Proprioception.

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 Atoh1-lineage neurons, whereas thoracolumbar Atoh1-lineage neurons project mostly locally within the spinal cord. Notably, while cervical and thoracolumbar Atoh1-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.SIGNIFICANCE STATEMENT 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 Atoh1-lineage neurons form mainly the indirect spino-lateral reticular nucleus and spino-olivary tracts and thoracolumbar Atoh1-lineage neurons project locally within the spinal cord, whereas only a few Atoh1-lineage neurons form a direct spinocerebellar tract.

Are paragriseal cells in the avian lumbosacral spinal cord displaced ventral spinocerebellar tract neurons?

In lumbosacral segments the spinal cord of birds contains numerous paragriseal neurons lying in the white matter of lateral and ventral funiculus. These paragriseal cells project to the cerebellum. Neurons of the dorsal horn (mainly Clarke's column) make up a dorsal spinocerebellar tract and neurons of the ventral horn (mainly spinal border cells) are at the origin of a ventral spinocerebellar tract. It was the aim of this investigation to look for the distribution of spinocerebellar ventral horn neurons and paragriseal cells in the thoracolumbosacral spinal cord of pigeons and to compare this distribution with that of the cervical enlargement. Neuroanatomical tracers were injected into the anterior cerebellum of pigeons and labeled spinal neurons were counted throughout the length of the spinal cord. In the cervical enlargement the number of spinocerebellar ventral horn neurons increases more rostral than that of dorsal horn neurons but the number of both groups of neurons decreases simultaneously at the caudal end of the enlargement. In the ventral horn of thoracolumbosacral segments the number of spinocerebellar ventral horn neurons and paragriseal cells increases again more rostrally than that of dorsal horn cells. However, the number of ventral horn cells decreases whereas that of paragriseal cells and of dorsal horn cells is maintained. This shows that the number of ventral horn cells decreases in favor of paragriseal cells, which supports the suggestion that paragriseal cells are displaced ventral horn spinocerebellar neurons. It is discussed whether the paragriseal neurons migrate toward their input.

Course of spinocerebellar axons in the ventral and lateral funiculi of the spinal cord with projections to the posterior cerebellar termination area: an experimental anatomical study in the cat, using a retrograde tracing technique.

The course of retrogradely labeled spinocerebellar fibers in the ventral and lateral funiculi of the spinal cord was studied following injections of wheat germ agglutinin-conjugated horseradish peroxidase into the posterior spinocerebellar termination area in the cat. Fibers labeled from unilateral injections into the paramedian lobule were found on the same side in the dorsal part of the lateral funiculus (DLF), corresponding to the dorsal spinocerebellar tract (DSCT), but contralaterally in the ventral part of the lateral funiculus (VLF) and in the ventral funiculus (VF), corresponding to the ventral spinocerebellar tract (VSCT). Following injections into the posterior vermis, labeled fibers were less numerous. Most of them were found in the DSCT and only very few in the VSCT. Previously identified cells of origin of these spinocerebellar tracts were labeled in these experiments and counted. They correlated well with the extents and the locations of the injections that had been made into the two termination sites. These results represent novel detailed information on the location of axons projecting to the two main posterior spinocerebellar termination sites in the spinal white matter in the cat.