ORCID
0009-0000-5207-8684
Date of Award
2025
Document Type
Thesis
Degree Name
Master of Science (MS)
Department
Pharmacology
First Advisor
Benedek Erdos
Second Advisor
Travis Todd
Abstract
Encounters with threats lead to fear or anxiety states, which elicit acute stress responses in the short term but enable chronic stress and promote maladaptive health outcomes in the long term. Brain-derived neurotrophic factor (BDNF) expression in the paraventricular nucleus of the hypothalamus (PVN) increases during acute and chronic stress and regulates the endocrine and autonomic branches of the stress response. Our lab has developed a rat model, the PVN-BDNF model, to study this component of the stress response by overexpressing BDNF with an AAV2 viral vector in the PVN (or GFP in controls). The PVN-BDNF model induces chronic activation of the autonomic and endocrine stress systems without introducing psychogenic threats, thereby separating physiological and psychological drivers of long-term stress-associated responses. This thesis uses the PVN-BDNF model to investigate how long-term activation of physiological stress pathways affects fear and anxiety behaviors. Three behavioral experiments were conducted: a) fear conditioning with renewal, b) light-enhanced acoustic startle, and c) the elevated plus maze (EPM). Immunofluorescence for the immediate-early gene c-fos was used to assess neuronal activity in the anterolateral bed nucleus of the stria terminalis (alBNST), a region critical to anxiety behaviors, and the central amygdala (CeA), which mediates fear responses. We found that hypothalamic BDNF reduced the conditioned freezing response and disrupted renewal, promoted active defensive behaviors to foot shock, and accelerated extinction learning. The acoustic startle response was higher at baseline and more potentiated by light in the PVN-BDNF rats compared to GFP controls. PVN-BDNF rats displayed more indicators of anxiety in the EPM and exhibited alterations in their exploration strategy with respect to controls. More c-fos positive nuclei were observed in the alBNST of PVN-BDNF rats than in controls, but there was no difference in the CeA. The results suggest that overexpressing BDNF in the PVN heightens BNST-dependent anxiety behaviors, attenuates conditioned freezing responses, and increases response vigilance to fearful stimuli. These findings demonstrate an anxiogenic role of hypothalamic BDNF and suggest the PVN may promote the progression to higher defensive states. This work advances our understanding of how the PVN, which is typically studied in the context of physiological stress, drives stress-associated behaviors.
Language
en
Number of Pages
100 p.
Recommended Citation
Van Horn, Sarah Hope, "The Effects of Hypothalamic Brain-Derived Neurotrophic Factor on Fear and Anxiety Behaviors" (2025). Graduate College Dissertations and Theses. 2152.
https://scholarworks.uvm.edu/graddis/2152