Date of Completion
Spring 5-1-2026
Thesis Advisor(s)
Sebnem Tuncdemir
Honors Major
Molecular and Cell Biology
Abstract
Post-Traumatic Stress Disorder (PTSD) is a psychiatric disorder that can develop following exposure to a traumatic event and is often characterized by impaired contextual discrimination, in which fear responses generalize to safe environments that resemble the original traumatic context. Previous studies have shown that elevated stress hormone levels during traumatic learning can impair memory specificity and promote generalized fear responses. The dentate gyrus (DG) of the hippocampus and adult-born granule cells (abGCs) are thought to play important roles in contextual discrimination and memory specificity. This study used contextual fear conditioning (CFC) paradigm in mice to investigate how enhanced stress and chemogenetic silencing of abGCs affect PTSD-like fear generalization behaviors. Corticosterone (CORT) administration prior to fear conditioning produced impaired contextual discrimination and increased freezing in neutral contexts during remote memory retrieval testing. No major sex differences were observed between male and female cohorts. Chemogenetic silencing of abGCs impaired contextual discrimination under low-stress conditions, supporting the role of adult neurogenesis in maintaining memory specificity. However, additional silencing of abGCs under enhanced stress conditions did not further worsen discrimination deficits, suggesting that stress-induced fear generalization may reach a ceiling effect. Additional cFos immunohistochemistry experiments revealed increased neuronal activation within the dentate gyrus and lateral entorhinal cortex following enhanced stress exposure, while elevated zero maze testing showed no significant differences in generalized anxiety-like behavior. Together, these findings demonstrate that elevated stress impairs contextual discrimination while adult-born granule cells improve memory specificity within dentate gyrus circuitry.
Accessibility Requirements
1
Recommended Citation
Malpure, Aditi, "Effects of Modifications to the Contextual Fear Conditioning Paradigm on Context Discrimination Deficits in Mice" (2026). Honors Scholar Theses. 1170.
https://digitalcommons.lib.uconn.edu/srhonors_theses/1170