Description du projet
Démêler la neurobiologie de la compulsion alimentaire induite par le stress
Les troubles de l’alimentation et l’obésité menacent la santé de diverses manières. L’hyperphagie boulimique a été associée à des perturbations des circuits neuronaux, mais des recherches supplémentaires sont nécessaires pour identifier des options de traitement efficaces pour cette maladie. Le projet ReCoDE, financé par l’UE, se concentrera sur la façon dont le stress modifie la force des connexions dans le cerveau impliqué dans la prise de décision et comment il peut déclencher un comportement alimentaire impulsif. En outre, il cherchera des moyens de remodeler ce processus par une manipulation spécifique de l’activité cérébrale. L’électrophysiologie, l’optogénétique et le traçage neuronal seront appliqués pour révéler si la compulsion alimentaire est due à des changements dans le contrôle du cortex préfrontal sur les circuits latéraux de l’hypothalamus qui régulent la prise alimentaire. Les résultats pourraient être prometteurs pour les traitements futurs des troubles alimentaires.
Objectif
Obesity and eating disorders are critical problems in society. Many patients with these brain diseases cope with stress by ravenous food intake (binge eating), which engenders new stress and maintains the pathology. Evidence-based treatments for this are urgently needed, but their implementation is hindered by a knowledge gap on: (i) which stress-driven neural disruptions cause binge eating, and (ii) whether these neural circuit changes can be normalized for therapeutic gain.
Studies in humans and rodents link binge eating to dysfunction of the prefrontal cortex (PFC), a brain region orchestrating the stress response. However, it is unknown how effects of stress on PFC output cause binge eating. The PFC prominently innervates the lateral hypothalamus (LHA), a region with a crucial role in managing food intake, yet little is known about the function of PFC regulation of the LHA. I predict that stress-induced binge eating requires a functional reorganization of prefrontal cortical control over lateral hypothalamus feeding circuits, and that this control can be restored to limit binge eating.
I propose a cutting-edge threefold strategy to address these hypotheses in mouse models:
1. I will unravel the make-up of PFC-LHA circuitry, combining electrophysiology, optogenetics and neural tracing. I will assess how stress functionally alters this complex network.
2. I will determine the concurrent activity at multiple sites within PFC-LHA circuitry as mice engage in stress-driven binge eating, using fiber photometric calcium recordings.
3. I will assess if normalizing stress-altered PFC-LHA synapses rebalances this circuitry in vivo and limits binge eating. For this I will combine optogenetic plasticity protocols, with fiber photometric measurements in freely moving mice.
Overall, this challenging project aims to unravel the unclear neurobiology of stress-induced binge eating. If successful, this would provide a key advance in understanding binge eating pathologies.
Champ scientifique
Mots‑clés
Programme(s)
Thème(s)
Régime de financement
ERC-STG - Starting GrantInstitution d’accueil
3584 CX Utrecht
Pays-Bas