Innovating Works

DrugsAndMemory

Financiado
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... 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. ver más
31/12/2028
1M€
Duración del proyecto: 62 meses Fecha Inicio: 2023-10-12
Fecha Fin: 2028-12-31

Línea de financiación: concedida

El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-10-12
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
ERC-2023-STG: ERC STARTING GRANTS
Cerrada hace 2 años
Presupuesto El presupuesto total del proyecto asciende a 1M€
Líder del proyecto
UNIVERSITATSKLINIKUM HEIDELBERG No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5