Date of Award
2024
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Psychology
First Advisor
Sayamwong E. Hammack
Abstract
Abstract Stress-related conditions, including trauma-related disorders, anxiety disorders, depressive disorders, and substance use disorders, along with the associated loss of productivity, cost the United States approximately $150 billion annually. Among these, anxiety disorders are the most common psychological disorders, affecting 33.7% of people at some point in their lives and imposing a significant economic burden on society. Current data suggest that pituitary adenylate cyclase-activating polypeptide (PACAP) and its specific receptor PAC1 in the bed nucleus of the stria terminalis (BNST) are critical for many behavioral and physiological consequences of stressor exposure, inducing anxiety-like behavior. We used chemogenetic approaches in PAC1-ires-Cre mice. Inhibiting PAC1 neurons dose-dependently reduced anxiety-related behaviors without reducing total locomotor activity, while stimulating PAC1 neurons had the opposite effect . Together with several control studies, these data indicate a key role for BNST PAC1 receptor activation in anxiety and stress. We also examine the projection targets of BNST PAC1 neurons. PAC1 neurons were observed in the anterior, posterior, and ventral regions of the BNST. We also observed mCherry expression in the nucleus accumbens (NAc), paraventricular nucleus of the thalamus (PVT), lateral habenula (LHb), lateral hypothalamus (LH), substantia nigra (SNR), and microcellular tegmental nucleus, consistent with other reports demonstrating that these brain regions receive BNST projections. These observations help to clarify the neural circuits involved in anxiety-like behavior. We also aimed to investigate the effects of chronic stress on PAC1-expressing cell activation. Unexpectedly, we did not observe anxiety-like behavior after chronic stress, inconsistent with our prior work. Examination of other anxiety-related behaviors, including grooming, rearing, and freezing, showed no significant differences between the groups. However, significant weight changes were observed in the chronic stress groups compared to the control and chemogenetic groups, indicating the impact of chronic stress. Lastly, we examined the PAC1-expressing neurons upstream of the BNST and found that these neurons receive projections from various brain regions, including the thalamic nucleus, lateral habenula, nucleus accumbens, basolateral amygdala, cingulate cortex, striatum, and substantia nigra. These data provide insight into the PAC1 circuit that modulates anxiety-like behavior. Our findings contribute to a better understanding of the mechanisms underlying anxiety disorders and emphasize the importance of further research in to PAC1 receptor pathway.
Language
en
Number of Pages
182 p.
Recommended Citation
Aktar, Mahafuza, "The Role Of Pac1 Receptors In The Bed Nucleus Of The Stria Terminalis (bnst) In Anxiety" (2024). Graduate College Dissertations and Theses. 1941.
https://scholarworks.uvm.edu/graddis/1941