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Olivocochlear and Peptide Signaling

The Vetter lab

The Vetter lab in the Department of Otolaryngology - Head and Neck Surgery is interested in how the cochlea defends itself against external stimuli that can result in noise-induced damage/loss of hearing. Because mammalian hair cells do not regenerate, it is vital to understand how the cochlea protects itself from noise challenges because the mechanisms involved may represent novel drug targets for clinical intervention, both retroactive and proactive, against noise-induced damage.

We are currently investigating two main biological signaling processes that are likely to be involved in protection. One is the olivocochlear system, an efferent system originating from cells located in the brainstem that sends its axonal projections out to the cochlea to innervate hair cells and their associated spiral ganglion cell processes. A second system that may be involved in protection against noise-induced damage is one we recently discovered, and represents a process involving cell signaling wholly localized / organized within the cochlea. This intrinsic signaling system is molecularly identical to the classic hypothalamic-pituitary- adrenal axis (the HPA axis). Briefly, we have discovered that the cochlea should be thought of as an extra-adrenal steroidogenic tissue, one of only a few such examples throughout the body. Thus, cells of the cochlea express all the steroid synthesis enzymes, and release both corticosterone and aldosterone in response to sound challenges. The cochlea expresses all the HPA axis signaling molecules upstream of steroid production, including the corticotropin releasing hormone (CRF), the CRF receptors, pro-opiomelanocortin (POMC), adrenocorticotropic hormone (ACTH), and the ACTH receptor MC2R.

We have begun a collaboration with the Zhou and Zhu labs to investigate the role of the CRF system in vestibular function as well. We have discovered that the CRF signaling system is expressed in the vestibular afferent pathway, but little is currently known of its functional significance.

Most recently, we have begun a collaboration with Dr. Fengwei Bai at the University of Southern Mississippi to examine the effects of Zika virus infection on the cochlea. Reports from Brazil indicate that adults infected with Zika experience bouts of temporary, or possibly even permanent hearing loss, but nothing is known of the cells involved in Zika’s damage to the cochlea.

Our lab maintains approximately 18 different mutant mouse lines we use for our studies. We use anatomical, molecular, and physiological approaches to study the olivocochlear system, the cochlear HPA signaling system, and Zika-associated damage. Examples of techniques used include immunostaining and confocal microscopy to analyze anatomical expression patterns during development and following trauma, ABR/DPOAE and single fiber recording to assess the functional state of both the cochlea and the vestibular systems, ELISA assays to assess protein expression and release from the cochlea, qPCR to quantify gene expression. Both short and long-term studies are possible. More information can be obtained by contacting Dr. Vetter.