structure de recherche

SOUMISSION D’UN SUJET DE THÈSE – ECOLE DOCTORALE VIE ET SANTÉ
UNITÉ : UPR 3212 - Institut des Neurosciences Cellulaires et Intégratives (INCI)
EQUIPE
Intitulé de l'équipe : Molecular determinants of pain
Responsable de l'équipe: Prof. Pierrick Poisbeau
E-mail : [email protected]
Téléphone : +33 (0)3 68 85 14 76
Site web éventuel : http://inci.u-strasbg.fr/fr/equ4/presentation.html
COMPOSITION DE L'ÉQUIPE
Nombre de chercheurs : 6
Nombre de ITA : 2
Nombre de doctorants : 4
Nombre de post-docs : 1
Autres : 2
CONCERNANT LA THÈSE
Nom du Directeur de thèse : Pascal Darbon
Mail du Directeur de thèse : [email protected]
Téléphone : +33 (0)3 88 45 67 45
Thèse en co-encadrement oui
Thèse en co-direction oui
Thèse en co-tutelle non
Nombre de thèses en cours pour le Directeur de thèse : 0
En cas de co-direction, co-encadrement ou co-tutelle :
Nom du co-directeur/encadrant : Alexandre Charlet ([email protected] ; +33 (0)6 07 08 25 06)
Université du co-directeur/encadrant : Université de Strasbourg
Nombre de thèses en cours pour le co-directeur/encadrant : 1
THÈSE(S) EN COURS POUR LE DIRECTEUR DE THÈSE
Nombre de thèses en cours : 0
Pour chaque doctorant en cours : Nom : Prénom : Début de la thèse : Fin prévisionnelle : -
SOUMISSION D’UN SUJET DE THÈSE – ECOLE DOCTORALE VIE ET SANTÉ
DOCTEURS ISSUS DE L'ÉQUIPE (durant les 5 dernières années)
Nom du docteur : Mouheiche
Prénom du docteur : Jinane
Date de soutenance : 22 décembre 2014
Situation actuelle : Postdoctorant
Nom du docteur : Zeitler
Prénom du docteur : Alexandre
Date de soutenance : 21 mars 2013
Situation actuelle : Enseignant titulaire du CAPES.
Nom du docteur : Aouad
Prénom du docteur : Maya
Date de soutenance : 2 novembre 2011
Situation actuelle : 3ème année de Médecine à l’Université de Strasbourg.
CONCERNANT LE SUJET PROPOSÉ
Titre :
Role of astrocyte voltage-gated ion channels in the astrocyte-neuron interactions
Projet :
Neuroscience research has identified the amygdala as a key target nucleus in the brain that is involved in
both anxiety and pain feeling. Amygdala is considered as the basis of the autonomous, behavioural and
emotional integrated response to pain (Neugebauer, Pain, 2007). It has been shown during past years that
oxytocin (OT), a well known hypothalamic neuropeptide, can specifically modulate the intra-amygdala
microcircuits (Viviani et al., Science, 2011) after being released by axons from OT neurons arising from
paraventricular, supraoptic and accessory nucleus of the hypothalamus (Knobloch et al., Neuron, 2012).
However, it is still unknown how precisely OT act at the cellular level. Some evidences point astrocyte as
a potential actor in OTergic signalling (Di Scala Gueno et al., Glia, 1994) and recent results obtain in the
lab indicate the involvement of astrocyte potassium and calcium voltage gated ion channels (Breton et al.,
Mol. Pain.,2009; Wahis et al, not published).
The present project aims to characterize involvement of astrocytes in the effects of OT in the amygdala
microcircuitry. Particularly, we aim at characterizing the role of voltage-gated ion channels in the intraand inter-cellular mechanisms involved in OT signalling.
In vitro effects of OT on membrane potential will be measured using patch clamp recordings of astrocyte
and neurons of the central amygdala, while general modulation of the astrocyte-neuron network will be
monitored using confocal calcium imaging, both in horizontal rat brain slices. In vivo and in vitro
modulation of the circuit by endogenous OT will be assessed using state of the art virus-induced
expression of red shifted ChR2 in OT neurons or in OTR carrier astrocytes.
The results of this project will contribute to the comprehension of the mechanisms of action of
neuropeptides as well as the evaluation of new potent therapeutic target will contribute to the elaboration
of new human and veterinary clinical use.
SOUMISSION D’UN SUJET DE THÈSE – ECOLE DOCTORALE VIE ET SANTÉ
Compétences souhaitées :
Relevant degree in neurosciences or a related field, serious interest for neuroanatomy, neurophysiology
and high motivation are mandatory.
Strong computer/programming skills as well as experience with electrophysiology patch-clamp and/or
calcium imaging will be considered as a serious advantage
Expertises qui seront acquises au cours de la formation :
Electrophysiology patch-clamp on slice, in vivo extracellular electrophysiology, slice calcium imaging,
behavior of pain and anxiety.
Article writing, oral communication, project management.
Mot clé (servira pour la consultation des sujets) :
Electrophysiology patch-clamp, calcium imaging, astrocytes, oxytocin, amygdala
PUBLICATIONS MAJEURES DE L'ÉQUIPE RELATIVES AU SUJET AU COURS DES 3
DERNIÈRES ANNÉES. SI NOUVEAU SUJET SANS PUBLICATION, MERCI D’INDIQUER 3
PUBLICATIONS RÉCENTES DU DIRECTEUR DE THESE.
1) Breton JD, Poisbeau P, Darbon P (2008) Antinociceptive action of oxytocin involves inhibition of
potassium channel currents in lamina II neurons of the rat spinal cord. Mol Pain. Nov 12;5:63
2) Viviani D, Charlet A, van den Burg E, Robinet C, Hurni N, Abatis M, Magara F, Stoop R (2011).
Oxytocin selectively gates fear responses through distinct outputs from the central amygdala. Science.
333(6038):104-7
3) Knobloch HS*, Charlet A*, Hoffmann LC, Eliava M, Khrulev S, Cetin AH, Osten P, Schwarz MK,
Seeburg PH, Stoop R, Grinevich V (2012). Evoked axonal oxytocin release in the central amygdala
attenuates fear response. Neuron. 73(3):553-66
CONTRATS DE L'ÉQUIPE
- Société Biocodex, Gentilly, France : contrat de partenariat et de recherche. P. Poisbeau ; 220 K€ (20122015)
- Expression and purification of human CGA. Cis-Bio; Y. Goumon; 45 K€ (2013)
- EU Marie Curie Reintegration grant (CIG 334455-Astrotamy): A. Charlet / P. Poisbeau; 100 K€
(2013-2016)
- IDEX Attractivity Univ of Strasbourg: A. Charlet; 130 K€ (2013-2015)
- USIAS Fellowship: A. Charlet; 230 K€ (2014-2016)
- PHC Procope: A. Charlet / V. Grinevich; 7K€ (2015)
- IDEX Interdisciplinarity Univ of Strasbourg: A. Charlet / M. Hibert; 50 K€ (2015-2016)
- Fondation Fyssen research grant: A. Charlet; 35 K€ (2015-2016)
SOUMISSION D’UN SUJET DE THÈSE – ECOLE DOCTORALE VIE ET SANTÉ
Partie à rédiger en anglais :
TOPIC
Title :
Role of astrocyte voltage-gated ion channels in the astrocyte-neuron interactions
Project :
Neuroscience research has identified the amygdala as a key target nucleus in the brain that is involved in
both anxiety and pain feeling. Amygdala is considered as the basis of the autonomous, behavioural and
emotional integrated response to pain (Neugebauer, Pain, 2007). It has been shown during past years that
oxytocin (OT), a well known hypothalamic neuropeptide, can specifically modulate the intra-amygdala
microcircuits (Viviani et al., Science, 2011) after being released by axons from OT neurons arising from
paraventricular, supraoptic and accessory nucleus of the hypothalamus (Knobloch et al., Neuron, 2012).
However, it is still unknown how precisely OT act at the cellular level. Some evidences point astrocyte as
a potential actor in OTergic signalling (Di Scala Gueno et al., Glia, 1994) and recent results obtain in the
lab indicate the involvement of astrocyte potassium and calcium voltage gated ion channels (Breton et al.,
Mol. Pain.,2009; Wahis et al, not published).
The present project aims to characterize involvement of astrocytes in the effects of OT in the amygdala
microcircuitry. Particularly, we aim at characterizing the role of voltage-gated ion channels in the intraand inter-cellular mechanisms involved in OT signalling.
In vitro effects of OT on membrane potential will be measured using patch clamp recordings of astrocyte
and neurons of the central amygdala, while general modulation of the astrocyte-neuron network will be
monitored using confocal calcium imaging, both in horizontal rat brain slices. In vivo and in vitro
modulation of the circuit by endogenous OT will be assessed using state of the art virus-induced
expression of red shifted ChR2 in OT neurons or in OTR carrier astrocytes.
The results of this project will contribute to the comprehension of the mechanisms of action of
neuropeptides as well as the evaluation of new potent therapeutic target will contribute to the elaboration
of new human and veterinary clinical use.
Wished skills:
Relevant degree in neurosciences or a related field, serious interest for neuroanatomy, neurophysiology
and high motivation are mandatory.
Strong computer/programming skills as well as experience with electrophysiology patch-clamp and/or
calcium imaging will be considered as a serious advantage
Expertises which will be acquired during the training:
Electrophysiology patch-clamp on slice, in vivo extracellular electrophysiology, slice calcium imaging,
behavior of pain and anxiety.
Article writing, oral communication, project management.
SOUMISSION D’UN SUJET DE THÈSE – ECOLE DOCTORALE VIE ET SANTÉ
Key word :
Electrophysiology patch-clamp, calcium imaging, astrocytes, oxytocin, amygdala
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