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Diurnality/nocturnality : functioning of wake promoting structures in physiological and pathophysiological conditions.

Research unit

UPR 3212 - Institut des Neurosciences Cellulaires et Intégratives (INCI)
5, rue Blaise Pascal, 67084 STRASBOURG

Group

Name: Régulation des horloges circadiennes

Group leader: CHALLET Etienne - challet@inci-cnrs.unistra.fr

Group leader's phone: 03 88 45 66 93

Group organization:
- Chercheurs: 3
- ITA: 2
- Doctorants: 3
- Post-Docs: 0
- Autres: 0

Publications of the team linked to the topic (3 last years):
1) Arble DM, Bass J, Behn CD, Butler MP, Challet E, Czeisler C, Depner CM,Elmquist J, Franken P, Grandner MA, Hanlon EC, Keene AC, Joyner MJ, Karatsoreos I, Kern PA, Klein S, Morris CJ, Pack AI, Panda S, Ptacek LJ, Punjabi NM,Sassone-Corsi P, Scheer FA, Saxena R, Seaquest ER, Thimgan MS, Van Cauter E,Wright KP. Impact of Sleep and Circadian Disruption on Energy Balance and Diabetes: A Summary of Workshop Discussions. Sleep. 2015 Dec 1;38(12):1849-60.
2) From daily behavior to hormonal and neurotransmitters rhythms: comparison between diurnal and nocturnal rat species. Cuesta M, Clesse D, Pévet P, Challet E.
Horm Behav. 2009 Feb;55(2):338-47

3) Daily rhythm of tryptophan hydroxylase-2 messenger ribonucleic acid within raphe neurons is induced by corticoid daily surge and modulated by enhanced locomotor activity.
Malek ZS, Sage D, Pévet P, Raison S.
Endocrinology. 2007 Nov;148(11):5165-72

About PhD

PhD Director: RAISON Sylvie - raison@unistra.fr

Phone: 03.88.45.66.84

Junior advisor: CIOCCA Dominique

Co-tutely: non

Co-Director: non

About PhD topic :

Title: Diurnality/nocturnality : functioning of wake promoting structures in physiological and pathophysiological conditions.

Project: In all Mammals a biological clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus, allows organisms to be in phase with environmental variations and governs the rhythmic pattern of numerous physiological functions.
According to whether an animal species is nocturnal (active during the night) or diurnal (active during the day), many rhythmic biological functions (sleep/wake cycle, food intake, hormonal secretions…) are in opposite phases. At present, the anatomical support and the cellular/molecular mechanisms underlying this specific temporal organization remain unknown.
Our group has previously shown that the intrinsic clock functions of the SCN are similar between nocturnal and diurnal species: the rhythmic patterns of the clock-genes expression, which are at the origin of the endogenous oscillations of the SCN, are similar and in phase in rats, as well as in Arvicanthis, a diurnal rodent, in spite of their opposite sleep/wake cycle (Challet 2007). Therefore, the actual hypothesis is that this nocturnality/diurnality would be downstream from the SCN, within nervous structures which integrate the temporal messages delivered by the clock (Kalsbeek et al., 2008) sending feedback input to the SCN (Cuesta. et al. 2009).
We propose to study and compare the temporal organization of several neurotransmission systems which constitute output and/or feedback of the clock between rats and Arvicanthis. To tackle this question, we will study serotoninergic (5-HT) neurons located in the Raphe nuclei, noradrenergic (NA) neurons of the Locus Coeruleus and orexinergic (Ox) neurons of the lateral hypothalamus which are involved both in the control of circadian functions and sleep/wake cycles.
The first part of our project is to compare several parameters reflecting the daily functioning of the monoaminergic (5-HT, NA), Ox and SCN neurons between rats and Arvicanthis. Several techniques will be used for this project: qPCR, in situ hybridization, western blot and immunohistochimy, to quantify the pattern of clock-genes expression and –proteins, as well as key enzymes of 5-HT, NA synthesis and Ox. Furthermore, we plan to quantify by HPLC the monoamine contents of several brain structures of interest after laser microdissection. The daily pattern of locomotor activity of these animals will be recorded using telemetry. All these methodological approaches and animal models are currently available for use at INCI and in the Chronobiotron.
In the second part of this project, we will evaluate (i) the impact of temporal disorganization of the animals (chronic jet-lag, light pulse) on the functioning of the wake-promoting structures, (ii) the adaptive responses of the circadian system in a 5-HT genetically modified model (tph2 -/- ; tph1/2 -/-). These results will be compared with those obtained in a physiopathological models of chronic stress known for affecting both the circadian system and the 5-HT system in particular via glucocorticoids, as we have previously demonstrated in the rat (Malek and al ., 2007).

Wished skills: Good knowledge in animal physiology and neurosciences.

Expertises which will be acquired during the training: Neuronal and endocrine mechanisms of the daily rhythmic functions.
Detection and quantification of the proteins (immunocytochimy, western blot) and of ARNm (in situ hybridization, qPCR). Laser microdissection of brain structures. HPLC detection (neuro-transmitters and their principal metabolites). Chirurgical implantation of specific sensors allowing to follow the body temperature.