Online

Moriarty, Samantha Kelly

Psychology

2023

M.A.

When dysregulated, neural systems important for fear behaviors can contribute to mental health disorders such as anxiety, phobias, and post-traumatic stress disorder (PTSD). In PTSD, a myriad of symptoms is possible, but a hallmark feature of the disorder is generalizing fear. This occurs when fear is experienced inappropriately in relation to the environment or circumstances. To study this behavior in rodent models, contextual fear conditioning is used. Contextual fear conditioning is a learning theory preparation where rodents are conditioned with an aversive stimulus such as foot-shock in one distinct context (A), while concurrently being exposed to a safe context (B). This training results in low fear behavior, usually measured in terms of freezing, in the safe context B, and high fear behavior in context A. This paradigm allows investigation of contextual discrimination, and also gives the experimenter the ability to observe context generalization, where the fear from the aversive context A extends to the safe context B. In this thesis, three experiments were performed. The purpose of the first experiment was to pilot a novel contextual fear conditioning paradigm so that it trained male rats to discriminate fearful and safe contexts. The second experiment served to extend this experimental design to include female rats, and therefore compare performance of males and females in contextual discrimination. Finally, the third experiment sought to expand on prior work demonstrating that pituitary adenylate cyclase activating polypeptide (PACAP), a peptide with strong associations to stress responses, significantly excites cells of the dentate gyrus. The dentate gyrus is a component of the hippocampus that is commonly thought to be involved in pattern separation, a process that may be integral to context discrimination. In addition, PACAP has been associated with aspects of PTSD, including symptom severity, particularly in women. With the connection of PACAP and PTSD as well as the dentate gyrus, experiment 3 aimed to test the result of a dentate gyrus PACAP infusion during a test session in either context A or B following the contextual fear conditioning design used in experiment 2. Experiment 1 showed that male rats could discriminate between contexts A and B in our experimental design. Experiment 2 built off of these results and extended the findings to females, showing that female rats also discriminated using this paradigm. Additionally, experiment 2 showed a sex difference between male and females, where male rats fear conditioned stronger than females, and females discriminated context better than males. Experiment 3 replicated these results in the first stage of conditioning. The results of the test day in experiment 3 showed that PACAP infused into the dentate gyrus had no effect on context discrimination in either male or female rats. Taken together, the experiments in this thesis show an experimental design that is capable of producing contextual discrimination, highlights possible sex differences in context fear conditioning, and suggests that if PACAP has an effect on generalization as our design measures it, it is likely not stemming from actions on the dentate gyrus.