Cerebrospinal fluid-contacting neurons in the regenerating spinal cord of lizards and amphibians are likely mechanoreceptors

During spinal cord (SC) regeneration in the tail of amphibians and lizards, small neurons in contact with the central canal and cerebrospinal fluid (CSF) are formed. The present review summarizes previous and recent studies that have characterized most of these neurons as cerebrospinal fluid-contacting neurons (CSFCNs), especially in the regenerating caudal SC of lizards. CSFCNs form tufts of stereocilia immersed in the CSF, secrete exosomes, and are often in contact with a secreted protein-rod indicated as Reissner fiber. Ultrastructural, autoradiographic, immunohistochemical, and behavioral studies strongly indicate that most of these cells are mechanoreceptors that differentiate from ependymal cells within 20–30 days after SC amputation. Numerous CSFCNs are gamma amino-butyric acid (GABA)-ergic, uptake amino acids, receive few synaptic boutons, and contain neurofilaments, fibroblast growth factor (FGFs), and other signaling proteins, the latter likely secreted into the central canal. Similar neurons are formed in the SC of the tuatara (Sphenodon puctatus), anurans, and urodeles during tail regeneration. In lizard, most of their projection remains in the SC close to the regenerated tail, but they form synapses with neurons that receive descending nerves from the brainstem, including vestibular nuclei. CSFCNs, aside a possible neurosecretory activity, might sense liquor movements for maintenance of balance, a role that is supported from recent studies on other caudate vertebrates. The regeneration of these cells also in the nervous system of other vertebrates remains unknown.