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bioRxiv · 10.1101/2022.08.15.501844

Cerebrospinal fluid-contacting neuron tracing reveals structural and functional connectivity for locomotion in the mouse spinal cord

Nakamura, Y.·Kurabe, M.·Matsumoto, M.·Sato, T.·Miyashita, S.·Hoshina, K.·Kamiya, Y.·Tainaka, K.·Matsuzawa, H.·Ohno, N.·Ueno, M.
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Abstract

Cerebrospinal fluid-contacting neurons (CSF-cNs) are enigmatic mechano- or chemosensory cells lying along the central canal of the spinal cord. Recent studies in zebrafish larvae and lampreys have shown that CSF-cNs control postures and movements via spinal connections. However, the structures, connectivity, and functions in mammals remain largely unknown. Here we developed a method to genetically target mouse CSF-cNs that highlighted structural connections and functions. We first found that intracerebroventricular injection of adeno-associated virus with a neuron-specific promoter and Pkd2l1-Cre mice specifically labeled CSF-cNs. Single-cell labeling of 71 CSF-cNs revealed rostral axon extensions of over 1800 m in unmyelinated bundles in the ventral funiculus and terminated on CSF-cNs to form a recurrent circuitry, which was further determined by serial electron microscopy and electrophysiology. CSF-cNs were also found to connect with axial motor neurons and premotor interneurons around the central canal and within the axon bundles. Chemogenetic CSF-cNs inactivation reduced speed and step frequency during treadmill locomotion. Our data revealed the basic structures and connections of mouse CSF-cNs to control spinal motor circuits for proper locomotion. The versatile methods developed in this study will contribute to further understanding of CSF-cNs functions in mammals.

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Nakamura, Y., Kurabe, M., Matsumoto, M., Sato, T., Miyashita, S., Hoshina, K., Kamiya, Y., Tainaka, K., Matsuzawa, H., Ohno, N., Ueno, M.. 2022-08-15. Cerebrospinal fluid-contacting neuron tracing reveals structural and functional connectivity for locomotion in the mouse spinal cord. https://doi.org/10.1101/2022.08.15.501844

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