CV Science

Didier DULON PhD in Neurosciences Director of Research

Course and current status

Education & Qualification

 

• PhD, Neuroscience, University of Bordeaux, Bordeaux, FR 09-1984 - 12-1987 

• Habilitation à Diriger des Recherches - HDR Thesis, Neurosciences, University of Bordeaux, Bordeaux, France 01-1989 - 06-1993 

 

Employment

• Postdoctoral Research, Kresge Hearing Research Institute, The University of Michigan, Ann Arbor, USA 12-1987 - 10-1989 

• Inserm Researcher, Inserm Unit229, Laboratoire Audiologie Expérimentale, Université de Bordeaux, Bordeaux, France 11-1989 - 09-1995 

• Visiting Scientist , School of Medicine, laboratory of otolaryngology, University of California San Diego, UCSD, San Diego, CA, USA 09-1995 - 10-1997 

• Research Director, INSERM EMI9927, University of Bordeaux, Bordeaux, France 10-1997 - 06-2005  

• INSERM Research Director, INSERM U1120, University of Bordeaux, Bordeaux, France 06-2005 - 09-2019 

• Team Leader INSERM Research Director, Institut de l'Audition Paris and University of Bordeaux, Institut Pasteur and Inserm, Paris, France 09-2019 ; Still ongoing

 

 

 

 

Scientific summary

In the last years, my research work addressed several key questions regarding the molecular mechanisms by which auditory hair cells control transmitter release at their ribbon synapses, a specific type of glutamatergic synapse found in the inner ear and retina only. These ribbon synapses are built for their specific ability to sustain the challenge of high rates of stimulation over a broad range of stimulus intensities. We showed that otoferlin (in which mutations lead to nonsyndromic hearing loss DFNB9) act as a key Ca2+-sensor, synaptotagmin-like, for controlling exocytosis of the glutamatergic synaptic vesicles in auditory inner hair cells (IHCs). We established that the sensitivity of otoferlin is similar in vestibular and cochlear hair cells and showed that it is the topographical organization of the Cav1.3 Ca2+ channels that determines the synaptic specificity of these sensory hair cells. We revealed the importance of a synaptic F-actin network in the topographical organization of the Cav1.3 channels at the IHCs active zones and showed a crucial interaction with the usher protein clarin-1. This F-actin network surrounds the active zone and controls the diffusion rate of the synaptic vesicles to the active zones. F-actin is also found to provide mechanosensitivity to the Cav1.3 channels when varying intracellular pressure. In our most recent published study, we demonstrated that various CaV1.3 channel isoforms control distinct components of the synaptic vesicle cycle in auditory inner hair cells and that viral AAV-therapy is working in a mouse model of usher-syndrome.

Innovative techniques: Molecular biology (q-PCR) - Electrophysiological measurements of mouse Auditory Brainstem Responses - Electrophysiological patch-clamp recordings of membrane ionic currents and capacitance (exocytosis) in cochlear hair cells from mouse organ of Corti ex-vivo - High resolution Confocal Ca2+ imaging in living cochlear hair cells- Intracellular UV- Ca2+ uncaging.

References

Dulon D, de Monvel JB, Plion B, Mallet A, Petit C, Condamine S, Bouleau Y, Safieddine S. A free intravesicular C-terminal of otoferlin is essential for synaptic vesicle docking and fusion at auditory inner hair cell ribbon synapses. Prog Neurobiol. 2024 Aug 3;240:102658. doi: 10.1016/j.pneurobio.2024.102658. Epub ahead of print. PMID: 39103114.

Leclère JC, Dulon D. Otoferlin as a multirole Ca²⁺ signaling protein: from inner ear synapses to cancer pathways. Front Cell Neurosci. 2023 Jul 19;17:1197611. doi: 10.3389/fncel.2023.1197611. PMID: 37538852; PMCID: PMC10394277.

Calvet C, Peineau T, Benamer N, Cornille M, Lelli A, Plion B, Lahlou G, Fanchette J, Nouaille S, Boutet de Monvel J, Estivalet A, Jean P, Michel V, Sachse M, Michalski N, Avan P, Petit C, Dulon D, Safieddine S. The SNARE protein SNAP-25 is required for normal exocytosis at auditory hair cell ribbon synapses. iScience. 2022 Nov 22;25(12):105628. doi: 10.1016/j.isci.2022.105628. PMID: 36483015; PMCID: PMC9722480.

Peineau T, Belleudy S, Pietropaolo S, Bouleau Y, Dulon D. Synaptic Release Potentiation at Aging Auditory Ribbon Synapses. Front Aging Neurosci. 2021 Oct 18;13:756449. doi: 10.3389/fnagi.2021.756449. PMID: 34733152; PMCID: PMC8558230.

Tertrais M, Bouleau Y, Emptoz A, Belleudy S, Sutton RB, Petit C, Safieddine S, Dulon D. Viral Transfer of Mini-Otoferlins Partially Restores the Fast Component of Exocytosis and Uncovers Ultrafast Endocytosis in Auditory Hair Cells of Otoferlin Knock-Out Mice. J Neurosci. 2019 May 1;39(18):3394-3411. doi:

Dulon, D., Papal, S., Patni, P., Cortese, M., Vincent, P. F. Y., Tertrais, M., Emptoz, A., Tlili, A., Bouleau, Y., MCV narratives, the ichel, V., Delmaghani, S., Aghaie, A., Pepermans, E., AlegriaPrevot, O., Akil, O., Lustig, L., Avan, P., Safieddine, S., Petit, C., & El-Amraoui, A. (2018).  Clarin-1 gene transfer rescues auditory synaptopathy in model of Usher syndrome. Journal of Clinical Investigation,128(8), 3382–3401. 

Michalski, N., Goutman, J. D., Auclair, S. M., Boutet de Monvel, J., Tertrais, M., Emptoz, A., Parrin, A., Nouaille, S., Guillon, M., Sachse, M., Ciric, D., Bahloul, A., Hardelin, J.-P., Sutton, R. B., Avan, P., Krishnakumar, S. S., Rothman, J. E., Dulon, D., Safieddine, S., & Petit, C. (2017). Otoferlin acts as a Ca2+ sensor for vesicle fusion and vesicle pool replenishment at auditory hair cell ribbon synapses. eLife,6. https://doi.org/10.7554/elife.31013 .

Vincent, P. F. Y., Bouleau, Y., Charpentier, G., Emptoz, A., Safieddine, S., Petit, C., & Dulon, D. (2017). Different CaV1.3 Channel Isoforms Control Distinct Components of the Synaptic Vesicle Cycle in Auditory Inner Hair Cells.The Journal of Neuroscience,37(11), 2960–2975. https://doi.org/10.1523/jneurosci.2374-16.2017 . RCR: 1.95 *. Dimensions Link*.

Vincent, P. F. Y., Bouleau, Y., Safieddine, S., Petit, C., & Dulon, D. (2014). Exocytotic Machineries of Vestibular Type I and Cochlear Ribbon Synapses Display Similar Intrinsic Otoferlin-Dependent Ca2+ Sensitivity But a Different Coupling to Ca2+ Channels. Journal of Neuroscience,34(33), 10853–10869.

Beurg, M., Michalski, N., Safieddine, S., Bouleau, Y., Schneggenburger, R., Chapman, E. R., Petit, C., & Dulon, D. (2010). Control of Exocytosis by Synaptotagmins and Otoferlin in Auditory Hair Cells.Journal of Neuroscience,30(40), 13281–13290.