Periodic Reporting for period 1 - MotiVTA (Characterizing opposing BNST to VTA circuits that differentially regulate motivation and individual responses to stress)
Reporting period: 2020-09-01 to 2022-08-31
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.
In the first set of studies, the researcher studied natural behavior patterns in mice under various stressors such as elevated platforms and synthetic predator odors. The researcher employed advanced techniques, including precise surgeries and viral infections, to examine how these stressors affected brain activity. The team adopted a virus-based approach, injecting a specific calcium sensor into the BNST, a brain region associated with stress and motivation. The goal was to understand how stressors influenced neural pathways and motivated behavior. This phase also involved refining behavioral protocols and selecting appropriate stressors.
In the second set of studies, the researcher manipulated the GABAergic BNST-VTA pathway, a neural connection linked to stress responses. Through a combination of surgeries and chemogenetic techniques, the researcher activated or inhibited this pathway in mice during motivated behavior tasks. Intriguingly, the researcher found that around 25% of mice exhibited low motivation, unrelated to anxiety. By manipulating specific neurons, researchers enhanced motivation in low performers while reducing it in high performers, providing valuable insights into the neural mechanisms underlying motivation.
In the third set of studies, the researcher investigated the role of endogenous corticotropin-releasing hormone (CRH) in behavioral modulation. By infusing specific compounds into the brain, they studied how CRH influenced motivated behaviors. The team also collected samples to analyze CRH mRNA expression levels, deepening their understanding of the molecular processes involved in stress-related behaviors.
In the operant conditioning task, a quarter of mice exhibited low motivation. Activating specific BNST projection neurons improved motivation in low performers, while inhibiting them reduced motivation in high performers, which suggest the existence of an inverted-U shape regulation of motivated behavior by the circuit under study. Manipulating corticotropin-releasing hormone (CRH) neurons in the BNST influenced motivation levels, demonstrating the intricate interplay between neural pathways and behavior.
This research advances our understanding of stress and motivation, and provides valuable insights into the neural mechanisms underlying these behaviors. These findings have the potential to impact future studies in neuroscience and mental health, offering new avenues for research and therapeutic interventions.
Furthermore, the researcher presented this work and attended several scientific events, including seminars and conferences, such as EBBS meeting in 2021 and BMI Symposia on memory and engaged with the wider scientific community, contributing to the collective understanding of stress, motivation, and behavior.
In a series of experiments, the researcher investigated natural behavior patterns in mice, utilizing advanced techniques such as behavioral analyses, combined with chemo genetic approaches. The researcher identified distinct neuronal activity patterns in response to stressors and behavioral tasks, shedding light on how stress influences motivated behaviors.
Remarkably, the study revealed that approximately 25% of mice displayed low motivation in tasks, and that this was not related to anxiety. Activating specific neurons improved motivation in low performers, while inhibiting them reduced motivation in high performers. These findings advanced our understanding of stress-related behaviors while highlighting the complexity of motivation regulation in different individuals.
While scientifically important, this research, despite its depth and complexity, does not directly translate into immediate socio-economic impact or wider societal implications. Its significance lies primarily within the realm of neuroscience, contributing valuable knowledge to the scientific community. Its impact on practical applications or broader societal issues may require further research and translation efforts.