Project description DEENESFRITPL Evidence-based drug addiction therapies Drug addiction exacts a staggering toll on society, with its pervasive neuropathological grip fuelling devastating personal and societal costs. The heart of this formidable challenge lies in the persistent tendency for relapse, particularly in environments linked to drug use. With this in mind, the ERC-funded DrugsAndMemory project aims to revolutionise our understanding and treatment of addiction. By unravelling the intricate neural circuitry connecting the motivation to consume drugs with the spatial and non-spatial facets of drug-associated contexts, this project promises groundbreaking insights crucial for preventing and reversing context-triggered drug-seeking behaviour. By employing cutting-edge techniques, including in vivo recordings and optogenetics, the project decodes the complex interplay of spatial and non-spatial cues driving drug-seeking behaviour. Show the project objective Hide the project objective Objective 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. Fields of science natural sciencesbiological sciencesneurobiologycognitive neuroscience Keywords Episodic memory contextual memory entorhinal cortex reward addiction drugs ventral tegmental area motivation nucleus accumbens circuitry optogenetics behaviour in vivo electrophysiological recordings Programme(s) HORIZON.1.1 - European Research Council (ERC) Main Programme Topic(s) ERC-2023-STG - ERC STARTING GRANTS Call for proposal ERC-2023-STG See other projects for this call Funding Scheme HORIZON-ERC - HORIZON ERC Grants Host institution UNIVERSITATSKLINIKUM HEIDELBERG Net EU contribution € 1 498 475,00 Address IM NEUENHEIMER FELD 672 69120 Heidelberg Germany See on map Region Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 498 475,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all UNIVERSITATSKLINIKUM HEIDELBERG Germany Net EU contribution € 1 498 475,00 Address IM NEUENHEIMER FELD 672 69120 Heidelberg See on map Region Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 498 475,00
