Sounding out cell diversity in the auditory system


March 2, 2021 - 12:00pm - 1:00pm
About the Speaker
Lisa Goodrich

Animals use their sense of hearing to detect danger, find food, and communicate with each other, often against a complicated and noisy backdrop of competing sounds. Sound information is initially encoded by the activity of a heterogeneous population of spiral ganglion neurons (SGNs) housed in the cochlea. Collectively, these functionally diverse SGNs capture the full dynamic range of sounds and improve detection of sounds when the environment is noisy. We study the origins and nature of this heterogeneity. Using single cell RNA-sequencing, we showed that there are three molecularly distinct populations of SGNs and that diversification is disrupted by the absence of hair cell-evoked activity. One key player is the transcription factor Runx1, which is expressed in a subset of SGNs in an activity-dependent manner. In Runx1 mutant mice, SGN composition is altered, though the total number of neurons is unchanged, offering a unique opportunity to learn how neuronal diversity contributes to the sense of hearing in vivo. We found that neuronal responses to sound are dramatically changed in these animals. Moreover, the observed changes fit well with predictions from computational models of activity in a cochlea comprised of only one SGN subtype. These studies establish Runx1 as an important mediator of activity-dependent consolidation of neuronal identity and provide new biological evidence that SGN diversity determines how sounds are encoded and communicated to the central nervous system.