Cerebellar molecular layer interneurons are dispensable for cued and contextual fear conditioning

Funding Information: We were supported by the Biotechnology and Biological Sciences Research Council grant BB/H001123/1 (P.W.), the Medical Research Council grants G1100546/2 and G0800399 (P.W.) and the University of Aberdeen (K.L.H.M.-P., M.W.-F., G.R. and P.W.). M.W.F. is currently supported by the Intramural Research Programme at the National Institute of Health, USA. Open Access funding enabled and organized by Projekt DEAL.Peer reviewedPublisher PD

Neuronal activity disrupts myelinated axon integrity in the absence of NKCC1b

Through a genetic screen in zebrafish, we identified a mutant with disruption to myelin in both the CNS and PNS caused by a mutation in a previously uncharacterized gene, slc12a2b, predicted to encode a Na+, K+, and Cl− (NKCC) cotransporter, NKCC1b. slc12a2b/NKCC1b mutants exhibited a severe and progressive pathology in the PNS, characterized by dysmyelination and swelling of the periaxonal space at the axon–myelin interface. Cell-type–specific loss of slc12a2b/NKCC1b in either neurons or myelinating Schwann cells recapitulated these pathologies. Given that NKCC1 is critical for ion homeostasis, we asked whether the disruption to myelinated axons in slc12a2b/NKCC1b mutants is affected by neuronal activity. Strikingly, we found that blocking neuronal activity completely prevented and could even rescue the pathology in slc12a2b/NKCC1b mutants. Together, our data indicate that NKCC1b is required to maintain neuronal activity–related solute homeostasis at the axon–myelin interface, and the integrity of myelinated axons