Collections > UNC Chapel Hill Undergraduate Honors Theses Collection > Sex differences in anxiety and fear learning behavior following genetic manipulation of the 5-HT1A receptor in the bed nucleus of the stria terminalis (BNST)

The bed nucleus of the stria terminalis (BNST) is a critical node in the fear and anxiety circuitry of the brain that plays a key role in an organism’s ability to respond to stress. Serotonin 1A (5-HT1A) receptor signaling in the BNST has been implicated in anxiety and fear-related behavior using acute pharmacological manipulations that target pre- and post-synaptic receptors (Levita et al., 2004; Gomes et al., 2012). The goal of this project is to elucidate the role of post-synaptic 5-HT1A receptors within the BNST in anxiety, fear, and depressive-like behavior using a genetic deletion approach that selectively targets postsynaptic 5-HT1A receptors. Viral vectors containing the gene for Cre recombinase and a fluorescent tag (AAV5-Cre-GFP) or a control vector (AAV5-GFP) were infused into the BNST of genetically modified male and female 5-HT1A receptor flox mice. One month later, behavior on the elevated plus maze (EPM), open field, forced swim, novelty-suppressed feeding and fear conditioning assays were assessed. The results of this project indicate that the genetic deletion of 5-HT1ARs in the BNST has an anxiolytic-like effect in the EPM but enhances fear consolidation and contextual fear following a tone-shock protocol in male mice. These seemingly discrepant results may reflect the fact that under low stress conditions (e.g. the EPM), deletion of the 5-HT1A receptor disinhibits BNST output neurons which are anxiolytic (Kim et al., 2013; Jennings et al., 2013). In high stress (e.g. footshock) conditions, local neurons are recruited which are both anxiogenic and fear-enhancing (Levita et al, 2004). Deletion of 5-HT1A receptors from these neurons potentiates their fear enhancing actions, resulting in an increase in fear consolidation and contextual fear. The behavioral phenotypes of the female mice following this genetic manipulation were less pronounced, which could be due to the anatomical differences of the BNST between male and female mice.