Lukas Rüttiger and Marlies Knipper: Does corticosterone affect auditory sound processing at the inner hair cell synapse?

Whenever the balance of physiological processes in our body is disturbed, a stress response can be triggered to restore homeostasis and to facilitate adaptation. Physiological challenge by environmental demands, positive stress and also traumatizing, damaging stress are known to influence acuity of sound perception in humans as well as acuity of cortical processing of auditory signals in animals. These influences are considered to originate in central brain regions. We recently observed beneficial and deteriorating effects of corticosterone on hearing that may result from directly affecting the inner hair cell (IHC) synapse. In the present application we address the question to the nature and function of such stress influences on auditory processing. We aim to identify the role of corticosteroid hormone receptor types, mineralocorticoid (MR) and glucocorticoid receptor (GR), at the inner hair cell level (1) through cell-specific deletion of MR and GR in conditional mouse models with deletions in either cochlea or brain, (2) through investigating the effect of MR/GR agonists/antagonists on hearing and sound processing in the mature organ, and (3) through testing presumptive acute MR/GR effects on single auditory fiber responses on cortical processing. A presumptive stress-induced effect on IHC synapse integrity or vulnerability would help to answer a long-standing open question of the localization of primary sites responsible for current clinical symptoms requiring therapies and provide possible novel tools for therapeutic intervention.

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