Corticotropin Releasing Factor Signaling in the Mammalian Cochlea: An Integrative Niche for Cochlear Homeostatic Balance Against Noise

Beyond hair cells, the cochlea is composed of many cell types, and most of these cells do not directly participate in converting the acoustic signal into neural responses sent onward to the brain. Many of these “support” cells exist in niches that position them to monitor the state of the cochlea, and some are situated to signal such information to systems outside the cochlea. Others occupy positions such that they can invoke cellular responses limited to the cochlea without the need for “outside help”. Inflammatory responses that occur in the inner ear are perhaps one of the best examples of this surveillance/reporting role served by the vast majority of cells in the cochlea. Understanding a complex event such as inflammation will require that we draw on many different aspects of biology. Here we will cover a wide range of topics that are likely to be of significance for understanding cochlear inflammation. These include a cochlear-based CRF signaling system that mirrors the hypothalamic-pituitary-adrenal axis, central Master clocks and peripheral clocks resident in many tissues of the body, and the molecular biology of glucocorticoids and glucocorticoid receptors. While seemingly disparate, as discussion of these topics unfolds, it will become obvious that understanding these signaling systems will be important in generating a model of cochlear inflammatory processes. Here, we seek not to cover the well-worn ground of inflammation biology. Rather, we seek to cover the signaling systems that may be involved in setting up the inflammatory state, its modulation, and its final resolution.