1.1 Molecular determinants of hair cell exocytosis

Inner hair cells transduce sound stimulation into neurotransmitter release onto auditory nerve fiber. However, the synaptic release from hair cells does not recapitulate the secretion from the central nervous system. To identify the molecular synaptic machinery, we are using multi-disciplinary approaches from molecular biology to cellular and system level physiology.

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Each 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 channel 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.

 

Here, top view of the explant organ of Corti across different focal planes. Tectorial membrane is evident by its striated appearance in the upper most plane. Below, outer hair cells and inner hair cells are distinguished by their V- and U-shape hair bundles. In the lower most plane, afferent fibers connecting the inner hair cell soma are conspicuous.



Major publications

Guillet et al., J. Neurosci. 36: 649-654, 2016
Sendin et al., Proc Natl Acad Sci U S A, 111(5):1999-2004, 2014
Nouvian et al., Nature Neuroscience, 14:411-3, 2011
Ruel et al., Am J Hum Genet, 83: 278-92, 2008
Nouvian J. Physiol. (London), 584: 535-542, 2007
Roux et al., Cell, 127: 277-289, 2006
Khimich et al., Nature, 434: 889-9, 2005

Collaborations

  • Marci Lesperance (Mighigan University, USA)
  • Tobias Moser (Goettingen University, Germany)
  • Salah El-Mestikawy (McGill University, Montréal)
  • François Rassendren (IGF, France)

Fundings

ANR 150 par 150

Audisan

 

Contact

Régis Nouvian