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Characterizing opposing BNST to VTA circuits that differentially regulate motivation and individual responses to stress

Project description

New biological insight into stress-related anxiety

Everyday stress may have a different impact on people, and some experience pathological responses, such as anxiety and depression. It is well established that anxiety correlates with the response of dopamine neurons to the stress-induced corticotropin-releasing hormone. The EU-funded MotiVTA project will work on two emerging neuronal pathways that also influence anxiety. The balance between these pathways seems to affect dopamine release and drive motivation in response to stress. Researchers will employ a variety of approaches to monitor and manipulate the activity of these pathways and elucidate their engagement in anxiety response.

Objective

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.

Coordinator

ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Net EU contribution
€ 191 149,44
Address
BATIMENT CE 3316 STATION 1
1015 Lausanne
Switzerland

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Region
Schweiz/Suisse/Svizzera Région lémanique Vaud
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 191 149,44