Fiche Projet - Complexité du vivant

Ecole Doctorale COMPLEXITE DU VIVANT – Fiche Projet CONCOURS
Nom et prénom du directeur de thèse (et si besoin du co-directeur) : Pr. Christine PETIT
Le directeur de thèse et le co-directeur doivent impérativement être habilités à diriger les recherches (HDR)
Coordonnées
Tel : 01 45 68 88 90
e-mail : [email protected]
Nom et prénom du co-encadrant (non HdR ) (s’il y a lieu) : Nicolas Michalski et Boris Gourévitch
Coordonnées Tel : 01 45 68 88 89
e-mail : [email protected] et [email protected]
Nom et prénom du responsable de l’équipe : Pr. Christine Petit
Nombre de chercheurs et enseignants-chercheurs statutaires de l’équipe titulaires d’une HDR :
3
Nom et prénom du responsable du laboratoire : Pr. Christine Petit
Intitulé du laboratoire et N° d’unité : INSERM UMR1120
Spécialité : Unité de génétique et de physiologie de l’audition
Titre du projet de thèse :Deciphering inhibitory circuits of the auditory cortex
Résumé du projet de thèse
Many animal species detect their prey and predators through sounds and vocalize for social
communication and behaviour. In particular, humans have developed an unparalleled ability to make
sense of sounds through spoken language and music. The mammalian auditory system is characterized
by its operating speed, and its extremely efficient encoding of spectrotemporal patterns in sounds. For
instance, the human auditory system can detect a 0.3% variation in sound frequency and two clicks
separated by only 10 microseconds. Moreover, sound information reaches the cortex within about 30
ms in humans, a much shorter time lag than for any of the other senses. The auditory system is
therefore the fastest sensory system and is continuously performing real-time processing, an essential
feature for following sound streams such as spoken language. However, the neural code behind
complex sound processing remains largely unknown.
At the level of primary auditory cortex, it is known that communication sounds elicit precise
temporal spike patterns. Such neural code is presumed to result from the interplay between neural
excitation and inhibition. Indeed, inhibitory interneurons respond with short latency, great temporal
precision and transient spiking to such sounds. However, inhibitory neuronal subpopulations are
uncharacterized. Moreover, the functional role of inhibition at the cortical level in processing complex
sounds is not completely clarified yet: for instance, blocking GABAA or GABAB inhibition has
controversial effects and does not necessarily reduce the temporal precision of neural response. A
potential role of inhibition could be to reduce information redundancy during the cortical processing of
complex sounds. Reduction of redundancy may even be a general principle of sensory systems when
progressing from the brainstem to the cortex. Moreover, the role of intracortical inhibition between the
auditory cortex and other sensory cortices just emerges and needs to be further assessed.
The goal of the PhD will be to identify and characterize functionally the role of inhibitory
subpopulations of the auditory cortex in processing noise and vocalization (speech) information. By
determining the molecular bar code of individual inhibitory neurons of the auditory cortex, the PhD
student will characterize and potentially identify new inhibitory neuron subpopulations in the auditory
cortex. Based on these molecular bar codes of these populations, the laboratory will develop new
mouse genetic tools targeting these specific subpopulations. The host laboratory has recently identified
a couple of mouse models, which have a deficit in particular inhibitory neuron subpopulations. The
final goal of the PhD project will be to characterize the modifications in spiking and local field activity
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Ecole Doctorale COMPLEXITE DU VIVANT – Fiche Projet CONCOURS
in the auditory cortex of these mutants, especially when processing noise and vocalization information,
by using multi-electrode in vivo recordings and to characterize the underpinning neuronal circuits.
Thèses actuellement en cours dans l’équipe
Nom et Prénom du doctorant
Labbé Ménélik
Baptiste Libé-Philippot
Nom du directeur de thèse
Christine Petit
Christine Petit
Année de 1ere
inscription et
Ecole Doctorale
2012
2013
Financement pendant la thèse
Labex ANR-10-LABX-65
Allocation spécifique – Ministère
de la Recherche
Trois publications récentes du directeur de thèse (du co-directeur ou du co-encadrant s’il y a lieu).Mettre en gras le nom
du directeur de thèse.
Hypervulnerability to Sound Exposure through Impaired Adaptive Proliferation of Peroxisomes.
Delmaghani S, Defourny J, Aghaie A, Beurg M, Dulon D, Thelen N, Perfettini I, Zelles T, Aller M, Meyer A,
Emptoz A, Giraudet F, Leibovici M, Dartevelle S, Soubigou G, Thiry M, Vizi ES, Safieddine S, Hardelin JP,
Avan P, Petit C.
Cell. 2015 Nov 5;163(4):894-906.
The CD2 isoform of protocadherin-15 is an essential component of the tip-link complex in mature auditory hair
cells.
Pepermans E, Michel V, Goodyear R, Bonnet C, Abdi S, Dupont T, Gherbi S, Holder M, Makrelouf M, Hardelin
JP, Marlin S, Zenati A, Richardson G, Avan P, Bahloul A, Petit C.
EMBO Mol Med. 2014 Jun 17;6(7):984-92.
An unusually powerful mode of low-frequency sound interference due to defective hair bundles of the auditory
outer hair cells.
Kamiya K, Michel V, Giraudet F, Riederer B, Foucher I, Papal S, Perfettini I, Le Gal S, Verpy E, Xia W, Seidler
U, Georgescu MM, Avan P, El-Amraoui A, Petit C.
Proc Natl Acad Sci U S A. 2014 Jun 24;111(25):9307-12.
Docteurs encadrés par le directeur de thèse ayant soutenu après septembre 2010 et publications relatives à leur sujet de thèse.
Mettre en gras le nom du directeur de thèse et celui du docteur.
Nom Prénom : CARBELOTTO Elisa
Date de soutenance : 2011
Durée de thèse (en mois): 48
Ecole Doctorale : ed3c
Publications :
Coupling of the mechanotransduction machinery and F-actin polymerization in the cochlear hair bundles.
Caberlotto E, Michel V, de Monvel JB, Petit C.
Bioarchitecture. 2011 Jul;1(4):169-174. Epub 2011 Jul 1.
Usher type 1G protein sans is a critical component of the tip-link complex, a structure controlling actin
polymerization in stereocilia.
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Ecole Doctorale COMPLEXITE DU VIVANT – Fiche Projet CONCOURS
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.
Proc Natl Acad Sci U S A. 2011 Apr 5;108(14):5825-30. Epub 2011 Mar 21.
Harmonin-b, an actin-binding scaffold protein, is involved in the adaptation of mechanoelectrical
transduction by sensory hair cells.
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.
Pflugers Arch. 2009 Nov;459(1).
Nom Prénom : Pepermans Elise
Date de soutenance : 2014
Durée de thèse (en mois): 48
Ecole Doctorale : Complexité du vivant
Publications :
The tip-link molecular complex of the auditory mechano-electrical transduction machinery.
Pepermans E, Petit C.
Hear Res. 2015 Dec;330(Pt A):10-7. doi: 10.1016/j.heares.2015.05.005. Epub 2015 Jun 3. Review.
The CD2 isoform of protocadherin-15 is an essential component of the tip-link complex in mature auditory hair cells.
Pepermans E, Michel V, Goodyear R, Bonnet C, Abdi S, Dupont T, Gherbi S, Holder M, Makrelouf M, Hardelin JP,
Marlin S, Zenati A, Richardson G, Avan P, Bahloul A, Petit C.
EMBO Mol Med. 2014 Jun 17
Localization of Usher 1 proteins to the photoreceptor calyceal processes, which are absent from mice.
Sahly I, Dufour E, Schietroma C, Michel V, Bahloul A, Perfettini I, Pepermans E, Estivalet A, Carette D, Aghaie A,
Ebermann I, Lelli A, Iribarne M, Hardelin JP, Weil D, Sahel JA, El-Amraoui A, Petit C.
J Cell Biol. 2012 Oct 15
Usher type 1G protein sans is a critical component of the tip-link complex, a structure controlling actin polymerization
in stereocilia.
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.
Proc Natl Acad Sci U S A. 2011 Apr 5
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