Mentor: Jennifer Quinn, Ph.D.

The prevalence of clinical conditions rooted in anxiety and trauma, such as posttraumatic stress disorder (PTSD), underscores the need for better understanding of the neural mechanisms involved with fear/threat and safety expression. The neural circuitry of fear learning and memory expression is well understood. However, investigations of the neural mechanisms of safety learning and its expression are limited. The paraventricular nucleus of the thalamus (PVT) and the lateral septum (LS) both contribute to resolving motivational conflict. There are robust, bidirectional projections between the PVT and the LS and both regions are implicated in the expression of learned safety. In the present project, we first demonstrated safety learning in a large sample of rats using a discrete safety stimulus in the presence of a threatening context. Male and female rats showed reduced freezing in the threatening context in the presence of the safety stimulus. Next, we selected a subset of males and females from threat and safety training conditions based on their performance. “Threat” animals were not trained using the safety stimulus and we selected a subset of animals that showed no change in freezing during the safety stimulus presentation in the test session. The “high safety” subset of animals were those safety-trained animals that showed the greatest decrease in freezing during the presence of the safety stimulus, compared to the context-alone period. The “low safety” subset of animals were those safety-trained animals that showed the least change in freezing during the safety stimulus, compared to the context-alone period. We evaluated c-Fos immunoreactivity in specific subregions of the PVT and LS. In the anterior and posterior PVT and dorsal/intermediate regions of LS, safety-trained animals showed reduced c-Fos expression compared to threat-trained animals, regardless of whether they demonstrated “high-safety” or “low-safety” in their freezing behavior during the test.

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