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Plasticity of central auditory circuits




The genetic approach, based on the study of hereditary forms of deafness, has proved particularly effective over the last 25 years for elucidating the molecular physiology of the cochlea, the sensory organ for hearing. By contrast, this genetic dissection has provided very little information to date about the central auditory system, even though dysfunctions of this system affect about 5% of children and more than 25% of the elderly. In addition, it has recently been discovered that hearing loss in middle age is a major risk factor for the subsequent development of dementia. People suffering from hearing loss have a risk of developing dementia later in life up to five times higher than that of people with normal hearing. However, the underlying biological processes are poorly understood.

Preliminary results obtained in mice suggest that central defects may coexist with cochlear defects in some genetic forms of deafness. These central defects have remained undetected until now due to the simultaneous presence of a cochlear defect depriving the auditory brain of some or all of the acoustic information it would normally receive. On the basis of current knowledge, it is not possible to determine the extent to which such central deficits can be generalized to all genetic forms of deafness and whether, in certain cases, they could account for the association between hearing loss and dementia.

The activity of the team is articulated around four priorities: 

  1. Generating an inventory of the genetic forms of deafness (classically peripheral) for which there are masked deficits of the central auditory system. 
  2. Deciphering the role of the associated genes in the development and functioning of the central auditory system.
  3. Establishing the auditory functions affected by defects of these genes.
  4. Finally, establishing, with the help of the CERIAH (the center for research and innovation in human audiology), whether the defects observed in mice are also present in humans. 

The results of our team will provide the basis for the exploration of auditory brain dysfunctions in patients with mutations of the genes responsible for these forms of deafness, and will make it possible to develop appropriate innovative auditory rehabilitation methods for these defects.






Nicolas Michalski, CR (researcher), Institut Pasteur


CR1, CNRS (CNRS researcher level 1)


Engineer, INSERM


Postdoctoral worker


Postdoctoral worker


PhD student


PhD student


(1) MICHALSKI, N., and Petit, C. (2019). Genes Involved in the Development and Physiology of Both the Peripheral and Central Auditory Systems. Annu. Rev. Neurosci. Review

(2) Libé-Philippot, B., Michel, V., Boutet de Monvel, J., Le Gal, S., Dupont, T., Avan, P., Métin, C.*, MICHALSKI, N.*, and Petit, C*. (2017). Auditory cortex interneuron development requires cadherins operating hair-cell mechanoelectrical transduction. Proc. Natl. Acad. Sci. U.S.A. 114, 7765–7774.
*Cosenior authors

(3) MICHALSKI, N., Goutman, J.D., Auclair, S.M., Monvel, J.B. de, Tertrais, M., Emptoz, A., Parrin, A., Nouaille, S., Guillon, M., Sachse, M., et al. (2017). Otoferlin acts as a Ca2+ sensor for vesicle fusion and vesicle pool replenishment at auditory hair cell ribbon synapses. ELife Sciences 6, e31013.

(4) Occelli F, Suied C, Pressnitzer D, Edeline JM, GOUREVITCH B (2016). A Neural Substrate for Rapid Timbre Recognition? Neural and Behavioral Discrimination of Very Brief Acoustic Vowels. Cereb Cortex. 2016 Jun;26(6):2483-2496. doi: 10.1093/cercor/bhv071. 

(5) GOUREVITCH B, Edeline JM, Occelli F, Eggermont JJ (2014). Is the din really harmless? Long-term effects of non-traumatic noise on the adult auditory system.
Nat Rev Neurosci. 2014 Jul;15(7):483-91. Review

(6) MICHALSKI, N., Babai, N., Renier, N., Perkel, D.J., Chédotal, A., and Schneggenburger, R. (2013). Robo3-driven axon midline crossing conditions functional maturation of a large commissural synapse. Neuron 78, 855–868.



Development and molecular physiology of the auditory cortex in normal and pathological conditions

In most cases of human deafness of genetic origin, the sensory organ for hearing, the cochlear, can account entirely for the hearing deficit of the patient. The fitting of a cochlear implant directly stimulating the auditory nerve, bypassing the sound processing step in the cochlea, generally restores hearing performance to satisfactory levels in most cases. However, in some cases, patients continue to display abnormal difficulties understanding spoken language. The researchers of this team have recently discovered that certain hereditary forms of deafness involve not only cochlear deficits, but also defects of the auditory cortex, the part of the brain responsible for analyzing auditory information.  Two cadherin-related proteins, cdhr15 and cdhr23, which are essential for the effective functioning of the cochlea, are also required for the migration and maturation of so-called “inhibitory” neurons in the brain. The affected neurons are specifically those colonizing the auditory cortex. This project aims to decipher the mechanisms underlying the development and functioning of this population of inhibitory neurons in the auditory cortex. The primary objective will be to identify the mechanisms underlying the expression of these cadherins both in the cochlea and in the brain, and to determine which other genes implicated in cochlear deafness might also play an intrinsic role in the brain. The researchers will then try to decipher the mechanisms by which these cadherin-related proteins guide the future inhibitory neurons specifically to the auditory cortex. Finally, they will characterize the roles of these inhibitory neurons in the processing of sound information. The results of this project will lay the foundations for the exploration of possible dysfunctions of the auditory brain in patients carrying mutations of the genes encoding these two cadherin-related proteins, and will make it possible to develop innovative auditory rehabilitation methods suitable for these auditory cortex defects. 


Nicolas Michalski – Principal investigator (ORCID:0000-0002-1287-2709)

(18) Tobin M., Chaiyasitdhi A., Michel V., MICHALSKI, N., Martin P. (2019). Stiffness and tension gradients of the hair cell's tip-link complex in the mammalian cochlea. Elife 8. pii: e43473. 

(17) MICHALSKI, N., and Petit, C. (2019). Genes Involved in the Development and Physiology of Both the Peripheral and Central Auditory Systems. Annu. Rev. Neurosci. Review

(16) Libé-Philippot B, Michel V , Boutet de Monvel J, Le Gal S, Dupont T, Avan P, Métin C*, MICHALSKI, N.*, Petit C*. *Co-senior authors (2017) Auditory cortex interneuron development requires cadherins operating hair cell mechanoelectrical transduction.Proc Natl Acad Sci USA 2017 Jul 13. (IF:9.4).

(15) MICHALSKI, N., Goutman, J.D., Auclair, S.M., Monvel, J.B. de, Tertrais, M., Emptoz, A., Parrin, A., Nouaille, S., Guillon, M., Sachse, M., et al. (2017). Otoferlin acts as a Ca2+ sensor for vesicle fusion and vesicle pool replenishment at auditory hair cell ribbon synapses. ELife 6, ppi: e31013.

(14) Kronander E, MICHALSKI, N., Lebrand C, Hornung JP, Schneggenburger R.(2017) An organotypic slice culture to study the formation of calyx of Held synapses in-vitro. PLoS One.12(4):e0175964.

(13) MICHALSKI, N., Petit C (2015) Genetics of auditory mechanotransduction. Pflugers Arch. Jan;467:49-72.

(12) Bonnet C, Louha M, Loundon N, MICHALSKI, N., Verpy E, Smagghe L, Hardelin JP, Rouillon I, Jonard L, Couderc R, Gherbi S, Garabedian EN, Denoyelle F, Petit C, Marlin S (2013) Biallelic nonsense mutations in the otogelin-like gene (OTOGL) in a child affected by mild to moderate hearing impairment. Gene Sep 25;527(2):537-40.

(11) Xiao L, MICHALSKI, N., Kronander E, Gjoni E, Genoud C, Knott G, Schneggenburger R (2013) BMP signaling specifies the development of a large and fast CNS synapse. Nat Neurosci. Jul;16(7):856-64. 

(10) MICHALSKI, N., Babai N, Renier N, Perkel DJ, Chédotal A, Schneggenburger R (2013) Robo3-driven axon midline crossing conditions functional maturation of a large commissural synapse. Neuron. Jun 5;78(5):855-68 (article distinguished by a Preview and the issue cover) 

(9) Delmaghani S., Aghaie A., MICHALSKI, N., Bonnet C., Weil D. and Petit C (2012) Defect in the gene encoding the EAR/EPTP domain-containing protein TSPEAR causes DFNB98 profound deafness. Hum Mol Genet. Sep 1;21(17):3835-44.

(8) Caberlotto E, Michel V, Foucher I, Bahloul A, Goodyear RJ, Pepermans E, MICHALSKI, N., Perfettini I, Alegria-Prévot O, Chardenoux S, Do Cruzeiro M, Hardelin JP, Richardson GP, Avan P, Weil D, Petit C (2011) Usher type 1G protein sans is a critical component of the tip-link complex, a structure controlling actin polymerization in stereocilia. Proc Natl Acad Sci U S A. Apr 5;108(14):5825-30. 

(7) Verpy E, Leibovici M, MICHALSKI, N., Goodyear RJ, Houdon C, Weil D, Richardson GP, Petit C (2011) Stereocilin connects outer hair cell stereocilia to one another and to the tectorial membrane.J Comp Neurol. Feb 1;519(2):194-210.

(6) Beurg M, MICHALSKI, N., Safieddine S, Bouleau Y, Schneggenburger R, Chapman ER, Petit C, Dulon D (2010) Control of exocytosis by synaptotagmins and otoferlin in auditory hair cells.J Neurosci. Oct 6;30(40):13281-90. 

(5) MICHALSKI, N., Michel V, Caberlotto E, Lefèvre GM, van Aken AF, Tinevez JY, Bizard E, Houbron C, Weil D, Hardelin JP, Richardson GP, Kros CJ, Martin P, Petit C (2009) Harmonin-b, an actin-binding scaffold protein, is involved in the adaptation of mechanoelectrical transduction by sensory hair cells. Pflugers Arch. Nov;459(1). 

(4) MICHALSKI, N., Michel V, Bahloul A, Lefèvre G, Chardenoux S, Yagi H, Weil D, Hardelin JP, Sato M and Petit C (2007) Molecular characterization of the ankle link complex in cochlear hair cells and its role in the hair bundle functioning. J Neurosci. Jun 13;27(24):6478-88. 

(3) Adato A, Lefevre G, Delprat B, Michel V, MICHALSKI, N., Chardenoux S, Weil D, El-Amraoui A, Petit C (2005) Usherin, the defective protein in Usher syndrome type IIA, is likely to be a component of interstereocilia ankle links in the inner ear sensory cells. Hum Mol Genet. Dec 15;14(24):3921-32. 

(2) Etournay R, El-Amraoui A, Bahloul A, Blanchard S, Roux , Pezeron G, MICHALSKI, N., Daviet L, Hardelin JP,Legrain P,Petit C (2005) PHR1, an integral membrane protein of the inner ear sensory cells, directly interacts with myosin1c and myosin7a. J Cell Science. Jul 1;118(Pt 13):2891-9. 

(1) Delprat B, Michel V, Goodyear R, Yamasaki Y, MICHALSKI, N., El-Amraoui A, Perfettini I, Legrain P, Richardson G, Hardelin JP, Petit C (2005) Myosin XVa and whirlin, two deafness gene products required for hair bundle growth, are located at the stereocilia tips and interact directly. Hum Mol Genet. Feb 1;14(3):401-10. 


Boris Gourévitch – Tenured researcher (ORCID: 0000-0001-6742-8739)

*the authors contributed equally

(35) Gnaedinger A., Gurden H., GOURÉVITCH B.*, Martin C.*, “Multisensory learning between odor and sound enhances beta oscillations”, Scientific Reports, 9: 11236, 2019.

(34) Occelli F., Hasselmann F., Bourien J., Eybalin, M., Puel J.L., Desvignes N., Wiszniowski B., Edeline J.M.*, GOURÉVITCH B.*, “Aged-related changes in auditory cortex without detectable peripheral alterations: A multi-level study in the Sprague Dawley rat.”, Neuroscience, 404:184-204, 2019.

(33) Adenis V., GOURÉVITCH B., Mammelle E., Recugnat M., Stahl P., Gnansia D., Nguyen Y., Edeline J.M., “Comparison between the eCAP growth functions obtained in guinea pig by increasing pulse amplitude or pulse duration: implications of the inter-animal variability.”, PLOS ONE, 13(8):e0201771., 2018.

(32) Gómez-Álvarez M.*, GOURÉVITCH B.*, Felix R.A., Nyberg, T., Hernández-Montiel, H.L., Magnusson A.K., “Temporal information in broadband sounds is conveyed by onset spiking in the Superior Paraolivary Nucleus”, European Journal of Neuroscience, 48(4):2030-2049, 2018.

(31) Felix II R., GOURÉVITCH B., Portfors C., “Subcortical pathways: towards a better understanding of auditory disorders.”, Hearing research, 362:48-60, 2018.

(30) Dugué G.P.*, Tihy M.*, GOURÉVITCH B., Léna C., “Cerebellar re-encoding of self-motion head kinematics”, eLife, 6:e26179, 2017.

(29) Felix R.A.*, GOURÉVITCH B.*, Leijon S.C.M., Gómez-Álvarez M., Saldaña E., Magnusson A.K., “Octopus cells in the posteroventral cochlear nucleus provide the main excitatory input to the superior paraolivary nucleus”, Frontiers in Neural Circuits, 11:37. doi: 10.3389/fncir.2017.00037, 2017.

(28) Ben Yahia B., GOURÉVITCH B., Heinzle A., Malphettes L., “Segmented linear modelling of CHO fed-batch culture and its application to large scale production.”, Biotechnology and Bioengineering, 114(4):785-797, 2017.

(27) GOURÉVITCH B., Cai J., Mellen N., “Cellular and network-level adaptations to in utero methadone exposure along the ventral respiratory column in the neonate rat.”, Experimental Neurology, 287(2):288-297, 2017.

(26) Occelli F., Suied C., Pressnitzer D., Edeline J.M., GOURÉVITCH B., “A neural substrate for rapid timbre recognition? Neural and behavioral discrimination of very brief acoustic vowels.”, Cerebral Cortex, 26(6):2483-2496, 2016.

(25) GOURÉVITCH B., Occelli F., Gaucher, Q., Aushana, Y., Edeline J.M., “Fast characterization of multiple encoding properties of auditory neurons”, Brain Topography, 28(3):379-400, 2015.

(24) GOURÉVITCH B., Edeline J.M., Occelli F., J.J. Eggermont, “Is the din really harmless? Long-lasting effects of non-traumatic noise exposure on adult auditory cortex”, Nature Reviews Neuroscience, 15(7):483-91, 2014.

(23) GOURÉVITCH B., Mellen N., “The preBötzinger complex as a hub for network activity along the ventral respiratory column in the neonate rat”, Neuroimage, 98:460-74, 2014.

(22) Gaucher Q., Huetz, C., GOURÉVITCH B., Édeline J.M. “Cortical inhibition reduces information redundancy at presentation of communication sounds in the primary auditory cortex”, Journal of Neuroscience, 33(26):10713-28, 2013.

(21) Gaucher Q., Huetz, C., GOURÉVITCH B., Laudanski, J., Occelli, F., Édeline J.M. “How do auditory cortex neurons represent communication sounds?”, Hearing Research, 305:102-12, 2013.

(20) De Cheveigné A., Edeline J.M., Gaucher Q., GOURÉVITCH B., "Component analysis reveals sharp tuning of the local field potential in the guinea pig auditory cortex", Journal of Neurophysiology, 109(1):261-72, 2013.

(19) GOURÉVITCH B., Brette, R., “The impact of early reflections on binaural cues”, Journal of the Acoustical Society of America, 132(1):9-27, 2012.

(18) Gaucher Q., Édeline J.M., GOURÉVITCH B., “How different are the local field potentials and spiking activities? Insights from multi-electrodes arrays.”, Journal of Physiology (Paris), 106(3-4):93-103, 2012.

(17) GOURÉVITCH B., Édeline J.M., “Age-related changes in the guinea pig auditory cortex: relationship with peripheral changes and comparison with tone-induced hearing loss”, European Journal of Neuroscience, 34(12):1953-65, 2011.

(16) Huetz C., GOURÉVITCH B., Édeline J.M., “Neural codes in the thalamocortical auditory system: from artificial stimuli to communication sounds”, Hearing Research, 271:147-158, 2011.

(15) GOURÉVITCH B., Kay L.M., Martin C., “Directional coupling from the olfactory bulb to the hippocampus during a go/no-go odor discrimination task”, Journal of Neurophysiology, 103:2633-2641, 2010.

(14) GOURÉVITCH B., Eggermont J.J., “Maximum decoding abilities of temporal patterns and synchronized firings: application to auditory neuron responses to click trains and amplitude modulated noise”, The Journal of Computational Neuroscience, 29(1-2):253-77, 2010.

(13) GOURÉVITCH B., Doisy T., Avillac M., Édeline J.M., “Follow-up of latency and threshold shifts of auditory brainstem responses after single and interrupted acoustic trauma in guinea pig”, Brain Research, 1304:66-79, 2009.

(12) GOURÉVITCH B., Noreña A., Shaw G., Eggermont J.J., “Spectro-temporal receptive fields in anesthetized cat primary auditory cortex are context dependent”, Cerebral Cortex, 19:1448-1461, 2009.

(11) Noreña A., GOURÉVITCH B., Pienkowski M., Shaw G., Eggermont J.J., “Increasing spectro-temporal sound density reveals an octave-based organization in cat primary auditory cortex”, Journal of Neuroscience, 28(36):8885-8896, 2008.

(10) GOURÉVITCH B., Eggermont J.J., “Spectrotemporal sound density dependent long-term adaptation in cat primary auditory cortex”, European Journal of Neuroscience, 27(12):3310-3321, 2008.

(9) GOURÉVITCH B., Le Bouquin Jeannès R., Faucon G., Liégeois-Chauvel C., “Temporal envelope processing in the human auditory cortex: response and interconnections of auditory cortical areas”, Hearing Research, 237(1-2):1-18, 2008.

(8) GOURÉVITCH B., Eggermont J.J., “A simple indicator of nonstationarity of firing rate in spike trains”, Journal of Neuroscience Methods, 163(1):181-187, 2007.

(7) GOURÉVITCH B., Eggermont J.J., “Evaluating information transfer between auditory cortical neurons”, Journal of Neurophysiology, 97(3):2533-2543, 2007.

(6) GOURÉVITCH B., Eggermont J.J., “A nonparametric approach for detection of bursts in spike trains”, Journal of Neuroscience Methods, 160(2):349-358, 2007.

(5) GOURÉVITCH B., Eggermont J.J., “Spatial representation of neural responses to natural and altered conspecific vocalizations in cat auditory cortex”, Journal of Neurophysiology, 97(1):144-158, 2007.

(4) GOURÉVITCH B., Le Bouquin Jeannès R., Faucon G., “Linear and nonlinear causality between signals: methods, examples and neurophysiological applications”, Biological Cybernetics, 95(4):349-369, 2006.

(3) Noreña A.*, GOURÉVITCH B.*, Aizawa N., Eggermont J.J., “Spectrally enhanced acoustic environment disrupts frequency representation in cat auditory cortex”, Nature Neuroscience, 9(7):932-939, 2006.

(2) Maby E., Le Bouquin Jeannès R., Liégeois-Chauvel C., GOURÉVITCH B., Faucon G., “Analysis of auditory evoked potentials parameters under radiofrequency fields using a support vector machines method”, Medical & Biological Engineering & Computing, 42(4):562-568, 2004.

(1) GOURÉVITCH B., Le Bouquin Jeannès R., “K-means clustering method for auditory evoked potentials selection”, Medical & Biological Engineering & Computing, 41(4):397-402, 2003.