Hair cell exocytosis

Auditory sensory hair cells release glutamate onto the afferent nerve fibers to refine the ascending auditory pathways during development and to transduce incoming sound-stimulation in adulthood. Here, we examine the mechanism underlying the autonomous and evoked synaptic release before and after the onset of hearing, respectively.

molecular determinants of hair cell exocytosis c s

 

Synaptic release in the hair cells. Inner hair cell synapse harbors a synaptic ribbon, a large organelle, which tethers a halo of glutamate-filled synaptic vesicles. In response to sound stimulation, hair cell depolarizes. The calcium influx through the voltage-gated calcium channels triggers the fusion of synaptic vesicles to the plasma membrane. Glutamate, released into the synaptic cleft, activates the postsynaptic glutamate receptors from the afferent auditory nerve fibers.

 
 
 
 
 

Wiring and activity of the auditory nerve fibers

To achieve a sound-coding over a large range of frequencies and intensities, the auditory nerve fibers differ in their activation threshold and in their distribution along the cochlear tonotopic axis. Here, we combine electrophysiology and computational modeling to determine the wiring and the weight of the fibers in the auditory nerve. This will enable to develop electrophysiological probes to map the distribution of the fibers in the auditory nerve and hence to detect hidden auditory loss.

.1 2 illustration 02

 
 
 
 

Computational simulation of the auditory nerve firing. Computational modeling of the sound-evoked firing of 807 fibers distributed along the tonotopic axis. At low-level of stimulation, basilar membrane response is sharply frequency-tuned and activates ANFs of a narrow band corresponding to sound probe frequency. In contrast, responses to intense stimuli are poorly tuned and recruit additional ANFs from broadband region with predominance toward the basal region of the cochlea.

 
 
 
 
 
 
 
 

Major publications

Harrus AG et al., Cell. Neurosci. 2018
Huet A et al., J Neurosci. 38(25):5727-5738, 2018
Guillet M et al., J Neurosci. 36(3):649-54, 2016
Surel C et al., eNeuro. 3(6), 2016
Sendin G et al., Proc Natl Acad Sci U S A.111(5):1999-2004, 2014

 

Collaborations

  • Sharon Kujawa, Harvard University, USA
  • Marci Lesperance, Michigan University, USA
  • Ruben Vidal, Indianapolis University, USA
  • Peter Heil, Würzburg University, Germany
  • Michèle Studer, Nice Sophia Antipolis University, France

 

Fundings

 

2.1 listen2.1 navyEpigenmed h110

ANR 150 par 150umontpellierfondation pour laudition 110x110

 

Contact

Nouvian Régis