and Abstract Fear-related stress and anxiety disorders manifest in millions of individuals throughout the world, many following a traumatic or frightening experience. While the symptoms of these disorders are well known, our lack of knowledge of how the brain encodes and modifies fear memories is not. How auditory and contextual memories are formed have been thoroughly studied in the past decades, however, research on aversive olfactory fear memories is relatively sparse. These experiments will determine the involvement of a novel circuit in the processing of olfactory fear memories. I have discovered a discrete circuit consisting of neurons projecting from the posterior medial cortical amygdala (pmCoA) to infralimbic division of the medial prefrontal cortex (IL). Silencing this pathway using chemogenetics prior to olfactory fear conditioning leads to a strengthening of a fear response to a conditioned odor.
Aim 1 proposes to determine what phases of aversive olfactory memory processing this circuit is involved in. To do this, I will silence this circuit prior to acquisition, consolidation, and extinction to determine the degree that this pathway has on each process.
Aim 2 will determine the activity of this circuit elicited by acquisition, consolidation, retrieval, and extinction of a learned odor. I will use fiber photometry to directly record calcium activity within the pmCoA neurons projecting the IL (pmCoA?IL neurons) to determine patterns of activation of this circuit during these different phases of aversive olfactory memory processing. These experiments could provide fundamental information on how olfactory fear memories are organized in the mammalian brain.
The experiments in this proposal will reveal novel circuits that modulate the encoding of learned fear of an odor. Our understanding of how the olfactory system functions with other systems of the brain involved in learning and memory are incomplete. These experiments will reveal how olfactory sensory signals that are relayed to the amygdala and prefrontal cortex contribute to the formation and maintenance of an aversive memory. This will increase our understanding of how odors can be potent retrieval cues for fear-related anxiety disorders and will have implications for advancing exposure-based therapy.
