H2020Индивидуална стипендия2020–2023

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

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2020-09-01 → 2023-10-20
Финансиране от ЕС: 191 149 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Невронните връзки между зоните BNST и VTA в мозъка определят защо при стрес някои хора стават по-мотивирани, а други изпадат в депресия. Разбирането на тези механизми помага при изучаването на тревожните разстройства и търсенето на подходящи терапии.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

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

This study explored the intricate relationship between stress, motivation, and individual differences in behavioral responses. Stressors, which trigger various physical and mental reactions, were investigated to understand how they affect motivation. In particular, the study addressed a paradox: while some people find motivation in stressful situations, others lose motivation, sometimes leading to conditions like depression, and attempted to uncover the underlying neural circuits governing these diverse responses, offering potential insights into stress-related disorders and therapeutic interventions. The study focused on the mesolimbic dopamine system, a crucial part of the brain linked to motivation and stress responses. The results showed that stressful situations lead to the release of a hormone called corticotropin-releasing hormone (CRH), which influences motivation by affecting specific brain cells. Interestingly, individuals with different levels of anxiety displayed varying motivated behaviors under stress, shedding light on the complexities of human responses. The study also investigated the role of a specific brain region called the anterior bed nucleus of the stria terminalis (BNST), known to be sensitive to stress. By exploring neural pathways within this region, the goal was to understand how stress affects different individuals, potentially shifting them from a calm to an anxious state. The study involved experiments in mice complemented by advanced techniques, including circuit analyses to monitor and manipulate brain activity during various behaviors. The experiments allowed identifying valuable insights into how BNST circuits influence motivated behavior and dopamine activity. This research holds importance for society as it deepens our understanding of stress-related disorders and offers potential avenues for therapeutic interventions. By unraveling the complex workings of the brain in response to stress, this study paves the way for future advancements in mental health treatments.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

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.

Оригинален текст от CORDIS (на английски).

Участници

ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE · LausanneКоординаторШвейцария