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Reshaping cortical circuits to decrease binge eating

Project description

Unravelling the neurobiology of stress-induced binge eating

Eating disorders and obesity threaten health in a variety of ways. Binge eating disorder has been linked to neural circuit disruptions, but further investigation is needed to find effective treatment options for this condition. The EU-funded ReCoDE project will focus on how stress alters the strength of connections in the brain involved in decision-making and how it can trigger impulsive eating behaviour. Moreover, it will search for ways to reshape this process by specific manipulation of brain activity. Electrophysiology, optogenetics and neural tracing will be applied, revealing whether binge eating occurs due to changes in prefrontal cortex control over lateral hypothalamus circuits which regulate food intake. Results may be promising for future treatments of eating disorders.

Objective

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.

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Topic(s)

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Funding Scheme

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ERC-STG - Starting Grant

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Call for proposal

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(opens in new window) ERC-2018-STG

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Host institution

UNIVERSITAIR MEDISCH CENTRUM UTRECHT
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 499 966,00
Address
HEIDELBERGLAAN 100
3584 CX Utrecht
Netherlands

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Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 499 966,00

Beneficiaries (1)

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