Neural correlates of safety learning

Accurate discrimination between safe and dangerous stimuli is essential for survival. Prior research has begun to uncover the neural structures that are necessary for learning this discrimination, but exploration of brain regions involved in this learning process has been mostly limited to males. Recent findings show sex differences in discrimination learning, with reduced fear expression to safe cues in females compared to males. Here, we used male and female Sprague Dawley rats to explore neural activation, as measured by Fos expression, in fear and safety learning related brain regions. Neural activation after fear discrimination (Discrimination) was compared between males and females, as well as with fear conditioned (Fear Only) and stimulus presented (Control) conditions. Correlations of discrimination ability and neural activation were also calculated. We uncovered a correlation between central amygdala (CeA) activation and discrimination abilities in males and females. Anterior medial bed nucleus of the stria terminalis (BNST) was the only region where sex differences in Fos counts were observed in the Discrimination condition, and the only region where neural activation significantly differed between Fear Only and Discrimination conditions. Together, these findings indicate the importance of fear expression circuitry in mediating discrimination responses and generate important questions for future investigation.