Persistent and distressing associative fear memories are a central feature of most anxiety and stress-related disorders. A key goal for research into anxiety and stress-related disorders is understanding how fear memories are initially strengthened. One way that memory has been shown to be enhanced is through stimulation of vagal afferent neurons and their brainstem projection site, the nucleus of the solitary tract (NTS). The NTS projects heavily to the bed nucleus of the stria terminalis (BNST), a limbic forebrain region which is widely connected with the amygdala and ventral hippocampus and has been shown to play a role in contextual fear memory. I hypothesize that consolidation of memory for contextual fear learning is modulated by a vagal afferent ? NTSNA ? BNST signaling pathway. In the proposed project, rats will undergo pharmacological or chemotoxin-based manipulation of vagal afferent signaling (Aim 1) or will undergo chemogenetic manipulations of NTSNA projections to BNST (Aim 2) during memory consolidation in a contextual fear conditioning paradigm. Memory retention will be quantified by assessing treatment effects on learned freezing behavior. This project will help develop a better understanding of the mechanism by which initial fear memories are strengthened, contributing to the development of therapies and treatments for anxiety and stress-related disorders. This project also provides a strong platform to expand and strengthen the trainee?s expertise in modern behavioral neuroscience approaches, including the use of a Cre-driver transgenic rat model, intersectional viral strategies for chemogenetic manipulation of neural circuits, and molecular phenotyping of circuit components.
Many anxiety and stress-related disorders are characterized by pervasive and intrusive fear memories. Memory consolidation, a key phase in memory formation, has been shown to be enhanced by vagal afferent signaling to the caudal brainstem. This basic science project will provide important information into the mechanism by which visceral sensory feedback to the brain contributes to fear memory consolidation, thereby contributing to the development of novel therapies and treatments for people with anxiety and stress-related disorders.
