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Characterization of nucleus accumbens neuronal activity and the role of its paraventricular thalamic afferents during the expression of cocaine-induced place preference

par De Groote, Aurélie
Président du jury Remmelink, Myriam
Promoteur de Kerchove d'Exaerde, Alban
Publication Non publié, 2023-07-05

Thèse de doctorat

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Résumé :

The nucleus accumbens (NAc) is a key component of the brain reward circuitry. Due to its extensive connectivity with regions involved in limbic but also motor processes, its main function is to integrate reward-related information, and to generate motivation to sustain action in goal-directed behaviors. As drugs of abuse hijack the brain reward system to drive compulsion to seek and consume drugs, characterizing NAc neuronal activity is particularly important to improve our understanding of the neuronal mechanisms of addiction. Here, we focused our research on a cocaine conditioned place preference paradigm, which relies on the association between drug and environmental cues to drive place preference. Indeed, the formation and maintenance of cue-reward associations drive strong craving and relapse after re-exposure of addicted individuals to a context previously paired with drug use. In this thesis, we first described the activity of the two main neuronal populations of the NAc, the medium spiny neurons expressing the dopamine receptor D1R or D2R (D1- and D2-MSNs, respectively), during this behavior by using in vivo endoscopic calcium imaging. We showed that both neuronal populations contain the same level of information about the place preference, and consistently encode the least preferred location, both before and after conditioning. As this location/preference-based encoding is likely shaped by presynaptic inputs, we developed a pipeline to identify and quantify NAc D1- and D2-MSNs brain-wide afferents, by using a retrograde tracing approach combined with optimized immunolabeling and clearing of whole brains. Finally, we demonstrated the functional involvement of the projections between the paraventricular thalamus and the NAc in the maintenance of these cocaine-associated memories, using chemo- and opto-genetic techniques. Altogether, the work realized during this thesis contributes to a better understanding of the circuits involved in addiction, and more particularly in one of the main driving forces of relapse, the drug-associated contextual memories.