Genetic targeting of myelinated primary afferent neurons using a new Nefh

Primary afferent neurons that convey somatosensory modalities comprise two large, heterogeneous populations: small-diameter neurons that give rise to slowly conducting unmyelinated axonal C fibers and medium-to-large diameter neurons with fast myelinated A fibers. Despite these two major groupings, tools to differentiate between unmyelinated and myelinated primary afferent fibers by genetic targeting have not been available; in particular, whereas numerous mouse driver lines exist to target different C fiber populations, genetic tools that target myelinated primary afferent populations are scarce. Here we describe a knock-in mouse line expressing tamoxifen-dependent CreERT2 under control of the Nefh gene, which encodes neurofilament heavy chain (NFH or NF200), a protein that is highly enriched in myelinated fibers. This mouse enables highly selective and efficient recombination of Cre-dependent reporters for functional and anatomical interrogation of myelinated fibers while excluding unmyelinated C fibers. In combination with other recombinase-expressing mouse lines, this genetic tool will be valuable for intersectional targeting of subpopulations of myelinated primary afferent fibers.