Team News



Sort by


PhD/HDR defense
17/03/2021 14h00
Adeline Cathala from Revest's lab (Thesis directed by Umberto Spampinato) will defend her thesis a presentation entitled 'Role of central serotonin receptors in the regulation of ascending dopaminergic pathways: implication in the effects of cocaine.'

from Revest's lab (Thesis directed by Umberto Spampinato) will defend her thesis a presentation entitled 'Role of central serotonin receptors in the regulation of ascending dopaminergic pathways: implication in the effects of cocaine.'

Link to the Zoom meeting will be sent on the liste.u1215 mailing list.

Abstract
This thesis investigates the functional role of the central serotonin receptor2B (5-HT2B) in the regulation of ascending dopaminergic (DA) pathways. Recent results from the laboratory have shown that 5-HT2B receptors differentially modulate ascending DA pathways. Indeed, 5-HT2B receptor antagonists reduce DA release in the nucleus accumbens (NAc), increase DA release in the medial prefrontal cortex (mPFC), and do not alter striatal DA release. This differential control of the mesocorticolimbic DA system involves a functional interaction between 5-HT2B receptors in the dorsal raphe (DR) and 5-HT1A receptors expressed in the CPFm, and results from activation of 5-HT neurons in the DR projecting to the CPFm. These results identified the RD as the major site of action of 5-HT2B receptors in controlling the activity of 5-HT and DA neurons. Furthermore, it was shown that blocking 5-HT2B receptors controls the neurochemical and behavioural responses induced by psychostimulants such as amphetamine, 3,4-methylenedioxymethamphine and cocaine, one of the most widely used drugs in the world. Thus, blocking 5-HT2B receptors suppresses the hyperlocomotion caused by cocaine. This effect, which occurs independently of DA release in the NAc and striatum, where DA activity is closely linked to cocaine-induced behavioural effects, may involve a postsynaptic interaction at the level of DA neurotransmission in subcortical regions. However, (1) the involvement of the CPFm DA in this interaction remains to be determined, given that this brain region is known to have anatomical and functional relationships with the NAc and striatum, and to be involved in cocaine behavioural responses. Furthermore, (2) the cellular localisation of 5-HT2B receptors within the DR and the cellular mechanisms underlying their interactions between the DA and 5-HT networks are unknown at the start of this thesis work.

Thus, the objective of this thesis is to address both of the above points. To this end, we studied the effects of two potent and selective 5-HT2B receptor antagonists (RS 127445 and LY 266097) on 5-HT and DA activity, using neurochemical, cellular and behavioural approaches in rats.

A first group of experiments provided anatomical and functional evidence that 5-HT2B receptors on the DR exert a tonic inhibitory control of 5-HT neurons innervating the CPFm, dependent on GABA interneurons. This 5-HT control is the first step in a complex poly-synaptic regulation leading to the differential control of mesocorticolimbic DA pathways. A second group of experiments shows that blocking 5-HT2B receptors in the DR inhibits cocaine-induced hyperlocomotion by acting at the level of DA neurotransmission in the NAc; this effect results from the potentiation of cocaine-induced DA release in the CPFm.

In conclusion, the work accomplished over the past three years provides substantial information regarding the functional role of the 5-HT2B receptor in the regulation of ascending DA pathways. Furthermore, our results not only improve the understanding of the DA and 5-HT interaction, but also highlight the therapeutic potential of 5-HT2B receptor antagonists for the treatment of cocaine addiction.

Key words: Serotonin, serotonin2B receptors, dopamine, cocaine, rat

Jury
Sgambato Véronique: Research Fellow (Lyon) - Rapporteur

Maroteaux Luc: Research Director (Paris) - Rapporteur

Cota Daniela : Research Director (Bordeaux) - Examiner

Voisin Daniel: University Professor (Bordeaux) - Examiner

Artigas Francesc: University Professor (Barcelona) - Guest

Spampinato Umberto: University Professor (Bordeaux) - Supervisor

Date de la soutenance: 17/03/2021 - 14h00
Lieu: Visioconférence Zoom

Pour plus de détails: https://www.bordeaux-neurocampus.fr/event/soutenance-de-theseadeline-cathala/



Hottopic
24/02/2021 10h00
Cristina MIRALPEIX from Cota's lab will give a presentation entitled "CB1 in POMC neurons and the regulation of food preferences"

Hottopic
16/12/2020 10h45
Agnès NADJAR from Cota's lab will give a presentation entitled "Nutrient sensing by microglial cells"

Job offers
03/11/2020
Postdoctoral position in Neurobiology of obesity and diabetes

We are searching for a highly motivated Postdoctoral researcher to join the research team Energy Balance and Obesity at the INSERM Unit 1215, Neurocentre Magendie (http://www.neurocentre-magendie.fr/cota) in Bordeaux, France.

The research focus of the team is the study of the neurobiology of obesity and diabetes. The project that the successful candidate will carry out aims at studying the molecular and functional heterogeneity of hypothalamic neurons implicated in food intake and body weight regulation.

This project is fully funded by an ANR (French National Research Agency) grant. The candidate will use specific genetic murine models, stereotaxic surgery, and viral approaches, associated with in vivo behavioral and metabolic assessments, molecular biology, and neuroanatomical analysis. The project will also involve the use of in vivo calcium imaging.

Candidates should have a doctoral degree in neuroscience/neurobiology/nutrition/or metabolism. Previous experience in the study of hypothalamic neuronal circuits in rodent models is preferred. The ability to work both independently and cooperatively within a team is essential.

The appointment is for 2 years, but candidates will be encouraged and guided to apply for additional funding opportunities. The position is available starting from April 2021.

Candidates should send their CV, motivation letter, list of publications, and 2 letters of reference to Dr. Carmelo Quarta (carmelo.quarta@inserm.fr) and Dr. Daniela Cota (daniela.cota@inserm.fr).




Hottopic
29/01/2020 10h30
Vincent SIMON from Cota's lab will give a presentation entitled ' "Uniting FISH and IHC techniques: a tale of wonder and despair"'

PhD/HDR defense
14/11/2019 14h00
de Thèse – Ashley Castellanos Jankiewicz Bile acids signaling as a novel mechanism in the hypothalamic control of energy balance

Bile acids signaling as a novel mechanism in the hypothalamic control of energy balance

Thesis supervisor:
Daniela Cota, MD, HDR

Summary: Bile acids (BA) are cholesterol-derived molecules mostly known for participating in the digestion of lipids. By activating the Takeda G protein coupled receptor 5 (TGR5) in peripheral organs, BA can also act as signaling molecules to reduce body weight, increase energy expenditure and improve glycaemia. These outcomes imply an anti-obesity function for TGR5. Since the major center of convergence of nutrient, hormonal, and environmental cues is the brain, particularly the hypothalamus, we hypothesized a role for TGR5 in this brain structure, specifically under diet-induced obesity.

Our results show that TGR5 and BAs transporters are expressed in the mediobasal hypothalamus (MBH), and that obese mice have decreased circulating and hypothalamic BA levels. Acute intracerebroventricular (ICV) or intra-MBH administration of TGR5 agonists reduced food intake and body weight in obese mice only, and improved insulin sensitivity. Accordingly, chronic ICV administration of the TGR5 agonist in obese mice reduced their body weight and adiposity, while increasing energy expenditure and markers of sympathetic activity in the adipose tissue. Indeed, experiments conducted at thermoneutrality (30°C) or chemical sympathectomy blunted these effects, demonstrating that central TGR5 effects require the engagement of the sympathetic nervous system. Conversely, by using genetic animal models, we observed that the deletion of TGR5 in the MBH rapidly increased food intake, body weight and adiposity, while blunting the sympathetic response to a cold challenge (4h at 4°C), hence worsening obesity.

Our work proves the existence of a functional hypothalamic BA – TGR5 receptor system. We show for the first time that the activation of TGR5 in the MBH decreases body weight and adiposity, while increasing energy expenditure through recruitment of the sympathetic nervous system. These results expose a new mechanism of action for potential anti-obesity therapies.

Keywords: Bile acids, TGR5, diet-induced obesity, mediobasal hypothalamus, energy balance, sympathetic activity, thermogenesis.
Date de la soutenance: 14/11/2019 - 14h00
Lieu: Neurocentre Magendie Seminar room


Hottopic
30/10/2019 10h30
Ashley CASTELLANOS JANKIEWICZ from Cota's lab will give a presentation entitled ' Bile acids signaling as a novel mechanism for the hypothalamic control of energy balance.'


mTORC1 and CB1 receptor signaling regulate excitatory glutamatergic inputs onto the hypothalamic paraventricular nucleus in response to energy availability

Wilfrid Mazier, Nicolas Saucisse, Vincent Simon, Astrid Cannich, Giovanni Marsicano, Federico Massa & Daniela Cota


Pièces jointes



The LabEx BRAIN Management Committee evaluated and selected, on Friday, July 5, the thesis welding scholarships. 12 applications had been submitted.

Ashley Castellanos Jankiewicz (Team Cota - Role of hypothalamic bile acid-TGR5 receptor signaling in the regulation of energy balance) and
Nanci Winke (Team Herry - Neuronal circuits involved in the emotional modulation of pain behavior) are among the winners!