Calcium homeostasis in parvalbumin DRG neurons is altered after sciatic nerve crush and sciatic nerve transection...

Reflex abnormalities mediated by proprioceptive sensory neurons after peripheral nerve injury (PNI) can limit functional improvement, leaving patients with disability that affects their quality of life. We examined postinjury calcium transients in a subpopulation of dorsal root ganglion (DRG) neurons consisting primarily of proprioceptors to determine whether alterations in calcium homeostasis are present in proprioceptors, as has been documented in other DRG neurons after PNI. Using transgenic mice, we restricted expression of the calcium indicator GCaMP6s to DRG neurons containing parvalbumin (PV). Mice of both sexes were randomly assigned to sham, sciatic nerve crush, or sciatic nerve transection and resuture conditions. Calcium transients were recorded from ex vivo preparations of animals at one of three postsurgery time points: 1-3 days, 7-11 days, and after 60 days of recovery. Results demonstrated that the post-PNI calcium transients of PV DRG neurons are significantly different than sham. Abnormalities were not present during the acute response to injury (1-3 days), but transients were significantly different than sham at the recovery stage where axon regeneration is thought to be underway (7-11 days). During late-stage recovery (60 days postinjury), disturbances in the decay time course of calcium transients in transection animals persisted, whereas parameters of transients from crush animals returned to normal. These findings identify a deficit in calcium homeostasis in proprioceptive neurons, which may contribute to the failure to fully recover proprioceptive reflexes after PNI. Significant differences in the calcium transients of crush versus transection animals after reinnervation illustrate calcium homeostasis alterations are distinctive to injury type.NEW & NOTEWORTHY This study examines calcium homeostasis after peripheral nerve injury in dorsal root ganglion (DRG) neurons expressing parvalbumin, a group of large-diameter afferents primarily consisting of proprioceptors, using two-photon calcium imaging in the intact DRG. Our findings identify aberrant calcium homeostasis as an additional source of sensory neuron dysfunction following peripheral nerve injury, uncover differences between two injury models, and track how these changes develop and resolve over the course of recovery.