Researcher(s)
- Simone Lunn, Neuroscience, University of Delaware
Faculty Mentor(s)
- Dayan Knox, Psychological And Brain Sciences, University of Delaware
Abstract
Post-traumatic stress disorder (PTSD) is an anxiety disorder that disrupts daily functioning following exposure to trauma. Women are more likely to develop PTSD than men, but the neurobiological mechanisms behind this sex difference are not fully understood. Animal models offer a powerful tool for studying these mechanisms, enabling examination of brain function before and after stress exposure, an advantage not possible in clinical research. This study investigates whether chemogenetic inhibition of the ventral hippocampus (vHipp) during traumatic stress alters fear extinction. Prior observations from our lab suggest that thalamic input to the vHipp responds to stress in a sex-dependent manner. These differences were first noted during vHipp inhibition in control animals and later extended to stressed groups, prompting further investigation into whether the effects reflect true neurobiological variation. Female rats underwent stereotaxic surgery and received either vehicle or clozapine-N-oxide (CNO) injections to inhibit vHipp activity using DREADDs (Designer Receptors Exclusively Activated by Designer Drugs). Behavioral testing included fear conditioning, extinction training, and extinction testing. CNO-treated rats exhibited higher freezing behavior and increased inhibitory avoidance, suggesting impaired extinction retention and potentially altered decision-making regarding perceived threat. Brain tissue was analyzed using immunohistochemistry for c-Fos, a marker of neural activation, and mCherry to confirm DREADD expression. Overall, these findings support a role for the vHipp in fear extinction and suggest that its inhibition during stress may interfere with adaptive fear regulation, potentially in a sex-dependent manner.