Chemical synaptic transmission in the cochlea.

The last two decades have witnessed major progress in the understanding of cochlear mechanical functioning, and in the emergence of cochlear neurochemistry and neuropharmacology. Recent models describe active processes within the cochlea that amplify and sharpen the mechanical response to sound. Although it is widely accepted that outer hair cells (OHCs) contribute to these processes, the nature of the medial efferent influence on cochlear mechanics needs further clarification. Acetylcholine (ACh) is the major transmitter released onto OHCs during the stimulation of these efferents. The inhibitory influence of this system is mediated by post- and presynaptic nicontinic and muscarinic receptors and the role of other neuroactive substances [gamma-aminobutyric acid (GABA), calcitonin gene-related peptide (CGRP), adenosine 5'-triphosphate (ATP) or nitric oxide (NO)] remains to be determined. The inner hair cells (IHCs) that transduce the mechanical displacements into neural activity, release glutamate on receptor-activated channels of AMPA, kainate, and NMDA types. This synapse is in turn controlled and/or regulated by the lateral efferents containing a cocktail of neuroactive substances (ACh, GABA, dopamine, enkephalins, dynorphin, CGRP). This glutamatergic nature of the IHCs is responsible for the acute destruction of the nerve endings and subsequently for neuronal death, damage usually described in various cochlear diseases (noise-induced hearing losses, neural presbycusis and certain forms of sudden deafness or peripheral tinnitus). These pathologies also include a regrowth of new dendritic processes by surviving neurons up to IHCs. Understanding the subtle molecular mechanisms which underly the control of neuronal excitability, synaptic plasticity and neuronal death in cochlear function and disease is a very important issue for the development of future therapies.