Light on a sensory interface linking the cerebrospinal fluid to motor circuits in vertebrates

The cerebrospinal fluid (CSF) is circulating around the entire central nervous system (CNS). The main function of the CSF has been thought to insure the global homeostasis of the CNS. Recent evidence indicates that the CSF also dynamically conveys signals modulating the development and the activity of the nervous system. The later observation implies that cues from the CSF could act on neurons in the brain and the spinal cord via bordering receptor cells. Candidate neurons to enable such modulation are the cerebrospinal fluid-contacting neurons (CSF-cNs) that are located precisely at the interface between the CSF and neuronal circuits. The atypical apical extension of CSF-cNs bears a cluster of microvilli bathing in the CSF indicating putative sensory or secretory roles in relation with the CSF. In the brainstem and spinal cord, CSF-cNs have been described in over two hundred species by Kolmer and Agduhr, suggesting an important function within the spinal cord. However, the lack of specific markers and the difficulty to access CSF-cNs hampered their physiological investigation. The transient receptor potential channel PKD2L1 is a specific marker of spinal CSF-cNs in vertebrate species. The transparency of zebrafish at early stages eases the functional characterization of pkd2l1⁺ CSF-cNs. Recent studies demonstrate that spinal CSF-cNs detect spinal curvature via the channel PKD2L1 and modulate locomotion and posture by projecting onto spinal interneurons and motor neurons in vivo. In vitro recordings demonstrated that spinal CSF-cNs are sensing pH variations mainly through ASIC channels, in combination with PKD2L1. Altogether, neurons contacting the CSF appear as a novel sensory modality enabling the detection of mechanical and chemical stimuli from the CSF and modulating the excitability of spinal circuits underlying locomotion and posture.