The role of cGMP signalling in auditory processing in health and disease.

cGMP is generated by the cGMP-forming guanylyl cyclases (GC), the intracellular nitric oxide (NO)-sensitive (soluble) guanylyl cyclase (sGC), and transmembrane GC (e.g. GC-A and GC-B). Summarizing the particular role of cGMP signalling for hearing, we show that GC generally do not interfere significantly with basic hearing function but rather sustain a healthy state for proper temporal coding, fast discrimination, and adjustments during injury. sGC is critical for the integrity of the first synapse in the ascending auditory pathway, the inner hair cell (IHC) synapse. GC-A promotes hair cell stability under stressful conditions such as acoustic trauma or ageing. GC-B plays a role in the development of efferent feed-back and gain control. Regarding the crucial role hearing has for language development, speech discrimination, and cognitive brain functions, differential pharmaceutical targeting of GC offers therapeutic promise for the restoration of hearing.