Peripheral basis of sound-exposure induced tinnitus

Université de Montpellier, Institut des Neurosciences de Montpellier, Inserm UMR 1051,
Hôpital Saint Eloi, 80 rue Augustin Fliche, 34095 Montpellier, France

To determine the neural basis of sound-exposure-induced tinnitus in the cochlea. Animals experiencing tinnitus will be selected using behavioural tasks (avoidance paradigm task, gap-detection). Next step will consist of investigating the electrical properties of the inner hair cells (IHCs) (patch-clamp, calcium imaging) and of the auditory nerve fibres (patch-clamp, single-unit, neural noise recording from the round window). Functional data will then be correlated to morphological investigations (confocal and 3D-electron microscopy). Altogether, the degree of tinnitus will be correlated to the functional and/or anatomical changes. Finally, defects in neural excitability and/or neural loss will be rescued using inner ear drug delivery.

From previous work we expect non-exclusive changes in connectivity and excitability of neurons in the cochlea. Indeed, following sound trauma, the efferent olivocochlear neurons that normally innervate afferent neurons instead connect to IHCs. Such synaptic plasticity could lead to a change in IHC activity via efferent neurotransmitters (Dopamine, GABA, Acetylcholine) that then might convey an aberrant message to the afferent neurons. This hypothesis will be probed at INM and UMG-GOE by IHC physiology. Additionally, we expect a drastic change of the excitability of afferent neurons through the loss of the efferent innervation and/or through the recruitment of NMDA receptors and this will be tested at the single neuron level. Finally, sound-trauma elicits a massive release of glutamate onto the auditory nerve fibres (ANFs), leading to excitotoxic injury. Such event can result into ANF loss and modify the whole transfer information from the cochlea to the brain. This hypothesis includes a detailed account of the innervation along the cochlea using immunohistochemistry. If true, changes in sensory input processing in higher auditory centres can be altered. Such assumption will be probed in collaboration with UMG-GOE, EMC and ULEIC. Finally, a rescue experiment will be performed: antagonist of ionic channels/GPCR and growth factor will be of prime interest to correct any defect in excitability and neuronal loss.


Prof. Jean-Luc Puel