Lateral olivocochlear neurons modulate cochlear responses to noise exposure

The sense of hearing originates in the cochlea, which detects sounds across dynamic sensory environments. Like other peripheral organs, the cochlea is subjected to environmental insults, including loud, damage-inducing sounds. In response to internal and external stimuli, the central nervous system directly modulates cochlear function through olivocochlear neurons (OCNs), which are located in the brainstem and innervate the cochlear sensory epithelium. One population of OCNs, the lateral olivocochlear (LOC) neurons, target spiral ganglion neurons (SGNs), the primary sensory neurons of the ear. LOCs alter their transmitter expression for days to weeks in response to noise exposure (NE), suggesting that they are well-positioned to tune SGN excitability over long time periods in response to auditory experience. To examine how LOCs affect auditory function after NE, we characterized the transcriptional profiles of OCNs and found that LOCs exhibit transient changes in gene expression after NE, including upregulation of multiple neuropeptide-encoding genes. Single nuclei were collected from animals 1 day or 7 days after exposure to a 110 dB, 8–16 kHz octave-band noise or from unexposed littermate controls, which remained in the vivarium. Samples were enriched for cholinergic olivocochlear neurons by dissecting the ventral brainstem of ChatCre{delta}Neo;Rosa26LSL-Sun1-GFP animals and using fluorescence-activated cell sorting to isolate GFP+ cells prior to encapsulation with the 10x Genomics 3’ Single-Cell Kit (v. 3.1). Each round of single-nucleus sequencing included pooled tissue from 3–5 ChatCre{delta}Neo;Rosa26LSL-Sun1-GFP mice of both sexes between 6–10 weeks of age. In each case, tissue from noise-exposed animals and unexposed littermate controls was collected simultaneously and run on parallel lanes of the same 10x Genomics microfluidic chip. Two independent collections for the 1 day post-exposure timepoint included a total of 8 unexposed (5 male, 3 female) and 9 noise-exposed mice (6 male, 3 female). Four collections for the 7 day post-exposure timepoint included 14 unexposed (7 male, 7 female) and 15 noise-exposed mice (8 male, 7 female).