The inner hair cell synaptic complex: physiology, pharmacology and new therapeutic strategies.
Within the cochlea, the sensory inner hair cells (IHCs), which transduce mechanical displacement of the basilar membrane into neural activity, release glutamate to act on postsynaptic receptor channels located on dendrites of primary auditory neurons. In turn the activity of the postsynaptic auditory dendrites is modulated by a variety of lateral efferent neurotransmitters. This presentation reviews the most recent findings obtained at the IHC synaptic complex with an original technique, namely coupling auditory nerve single unit recordings with multibarrel intracochlear perfusions. Two types of results are emphasized: (1) in physiological conditions, the activity of auditory nerve fibers involves AMPA, but not kainate or NMDA receptors, and (2) this activity is tonically modulated by dopamine, one of the lateral efferent neurotransmitters. With the increasing knowledge of molecular mechanisms involved at the first synaptic complex in the cochlea, it is now possible to envisage local treatments for spiral ganglion neurons. These treatments, available experimentally, may be used in the near future: either to protect spiral ganglion neurons against excitotoxic injury (traumatic and/or ischemic sudden deafness), or to prevent excitotoxic-induced hyperexcitability (probably the starting point of most posttraumatic tinnitus), or to delay neuronal death (neural presbycusis).
Puel
Jean-Luc
JL
Laboratoire de Neurobiologie de l'Audition-Plasticité synaptique, INSERM UMR-254, Université Montpellier-1, Montpellier, France.
Ruel
Jérôme
J
Guitton
Matthieu
M
Wang
Jing
J
Pujol
Rémy
R
D000818:Animals; D003056:Cochlear Nerve / Q000503:physiopathology*; D004298:Dopamine / Q000502:physiology*; D006199:Hair Cells, Auditory, Inner / Q000503:physiopathology*; D006801:Humans; D009473:Neuronal Plasticity / Q000502:physiology; D018091:Receptors, AMPA / Q000502:physiology*; D013136:Spiral Ganglion / Q000503:physiopathology; D009435:Synaptic Transmission / Q000502:physiology*; D014012:Tinnitus / Q000503:physiopathology
D018091:Receptors, AMPA; D004298:Dopamine