Descrizione del progetto
Nuove informazioni biologiche sull’ansia correlata allo stress
Lo stress di tutti i giorni può avere diverse conseguenze sulle persone e taluni avvertono risposte patologiche, quali ansia e depressione. È risaputo che l’ansia è correlata con la risposta dei neuroni dopaminergici all’ormone di rilascio della corticotropina indotto dallo stress. Il progetto MotiVTA, finanziato dall’UE, lavorerà su due vie neuronali emergenti, anch’esse in grado di influire sull’ansia. L’equilibrio tra tali vie sembra ripercuotersi sul rilascio di dopamina e orientare la motivazione in risposta allo stress. I ricercatori utilizzeranno diversi approcci per misurare e manipolare l’attività di queste vie, oltre a chiarire il loro coinvolgimento nella risposta all’ansia.
Obiettivo
In our daily life, we face many challenges that create stressful situations. Some individuals experience stress as motivational drive, whereas in others, it can reduce motivation and trigger avoidance behavior. Pathological responses to stress, such as depression and anxiety, take an enormous toll on society. Despite the relevance of stress on mental health, little is understood about the neuronal circuit mechanisms that underlie the behavioral differences in stress responsivity and why some individuals are more resilient to the negative impact of stress than others. The mesolimbic dopamine system plays a major role in the stress response. Work in the host lab found that trait anxiety influences how an individual’s motivated behaviors change with stress and that the anxiety level correlates with differences in the response of dopamine neurons in the ventral tegmental area (VTA) to the stress-induced neuropeptide CRH. Recently, two parallel pathways from the basal nucleus of stria terminalis (BNST) to the VTA –one glutamatergic and the other GABAergic– have been identified and are thought to influence anxiety and motivated behaviors. However, solid evidence linking activity in these pathways to behavioral outcomes is lacking. The goal of this proposal is to monitor and manipulate the activity of these pathways using a combination of optogenetics, calcium imaging, and behavioral testing. I hypothesize that the glutamatergic and GABAergic BNST-VTA pathways are differentially engaged during stress. The balance between these pathways modulates dopamine release from the VTA, which then determines whether an individual would experience increased or decreased motivation in response to stress. I will first determine the natural activity pattern of VTA-projecting BNST neurons and then investigate the consequences of activation or inhibition of this circuit on motivated behaviors and the role of CRH in the modulation of this circuit using genetic tools and neuropharmacology.
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Meccanismo di finanziamento
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinatore
1015 Lausanne
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