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DrugsAndMemory

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How do drug-associated contexts drive behaviour? The role of entorhinal circuit...

How do drug-associated contexts drive behaviour? The role of entorhinal circuitry in addiction Addiction to drugs is a ubiquitous neuropathological disease that inflicts immense societal costs. A core aspect of addiction that poses a major challenge for treatment is the propensity to relapse in environmental contexts that a... see more

31/12/2028

UKHD

1M€

Project Budget: 1M€

Project leader

UNIVERSITATSKLINIKUM HEIDELBERG No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

PARTICIPATION DEPralty Sin fecha límite de participación.

Financing granted El organismo HORIZON EUROPE notifico la concesión del proyecto The day 2023-10-12

ERC-2023-STG: ERC STARTING GRANTS Scope:Objectives

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characteristics of the participant

Este proyecto no cuenta con búsquedas de partenariado abiertas en este momento.

Private Information

No hay información privada compartida para este proyecto. Habla con el coordinador.

1 Participantes

UKHD

1.50M€ | Leader

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Project duration: 62 months Date Start: 2023-10-12
End date: 2028-12-31

Project leader

UNIVERSITATSKLINIKUM HEIDELBERG No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Project Budget 1M€

participation deadline Sin fecha límite de participación.

Project description Addiction to drugs is a ubiquitous neuropathological disease that inflicts immense societal costs. A core aspect of addiction that poses a major challenge for treatment is the propensity to relapse in environmental contexts that are associated with drug use. Identification and mechanistic characterization of novel addiction-relevant circuitry linking the motivation to take drugs to the complex spatial and non-spatial features that constitute a drug-associated context are at the core of this proposal. These insights will be used to identify the best constellation of anatomical targets to prevent and reverse the expression of context-triggered drug-seeking. The medial and lateral entorhinal cortex (MEC and LEC) are two central components of the episodic memory system integrating all features relevant for the formation of contextual memory. Crucially, MEC and LEC receive strong bottom-up dopaminergic input from the midbrain and send top-down projections to the nucleus accumbens (NAc). The dopaminergic system is the primary target of all addictive drugs. We will 1) study how bottom-up dopaminergic projections are implemented into drug-context associations in MEC and LEC and 2) determine how these associations influence NAc-mediated drug-seeking behaviour. We will utilize a multidisciplinary approach by developing electrophysiological in vivo recording paradigms in behaving mice that allow the assessment of complex spatial, contextual and non-spatial codes in conditioned place preference and self-administration paradigms typically used to model addiction in rodents. This will be combined with optogenetically-assisted circuit analysis of molecularly-defined pathways to link identified functions to the underlying circuitry. Pathway-specific optogenetic silencing will be used to prevent and reverse the manifestations of drug use on a neuronal and behavioural level. This will guide the evidence-based development of therapies in the future, such as deep-brain stimulation.

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