Neural activation during cat odor-induced conditioned fear and 'trial 2' fear in rats

Exposure to cat odor, an innate threat stimulus for rats, engages a conditioning process whereby the environment in which the odor was experienced comes to elicit fear. Additionally, response to cat odor appears to change with repeated exposure, with benzodiazepines having an anxiolytic effect upon first, but not second, cat odor exposure. We explored the neural correlates of these two phenomena using Fos immunohistochemistry. Rats were exposed to cat odor (a worn cat collar) and were allowed to hide from this stimulus. A ‘trial 1’ group was perfused after a single exposure, and a ‘trial 2’ group after two exposures. A ‘context’ group was exposed to cat odor once, then perfused after re-exposure to the odor-paired context. Trial 1, trial 2 and context groups showed similar defensive responses including avoidance and hiding. The trial 1 group showed Fos expression in limbic, hypothalamic and brainstem regions associated with defensive behavior. The trial 2 group showed a similar pattern although with less activation in the lateral septum, anterior and ventromedial hypothalamus, and dorsolateral periaqueductal gray. The context-exposed group showed Fos expression in a subset of the regions activated by cat odor itself: the dorsal premammillary nucleus, ventrolateral periaqueductal grey, cuneiform nucleus and locus ceruleus. Little activation was seen in the amygdala or hippocampus. These results show that stimuli associated with predatory threat come to activate similar brain regions to the threat stimulus itself.