Emotional states influence the manner in which stimuli are interpreted. Higher levels of state anxiety in humans leads to a more negative, or threatening, interpretation of novel, ambiguous information. Additionally, this is often followed by activation of the amygdala, an area known to be important in fear in both humans and animals. This dissertation aimed to determine whether the brain circuitry active during states of fear in rats might also be active during states of anxiety. Differential levels of state anxiety were manipulated during handling, which was confirmed using an open field test. Behavioral differences were not seen in fear conditioned freezing. Animals with both high and low levels of state anxiety were either exposed to novel chambers without footshock or were contextually fear conditioned with a footshock. Expression of the immediate-early gene, egr-1, known to be important in learning during fear conditioning, was then measured in the lateral nucleus of the amygdala, dorsal hippocampus, and prefrontal cortex: all areas known to be important in both fear and anxiety.
In the lateral nucleus of the amygdala, egr-1 increased following contextual fear conditioning. However, in animals with high levels of state anxiety, egr-1 also increased following exposure to a novel context. Conversely, in animals with low levels of state anxiety, egr-1 did not show an increase in response to exposure to a novel context. In the dorsal hippocampus, egr-1 did not show changes in area CA3 or in the dentate gyrus in following exposure to a novel context or fear conditioning. However, in area CA1, egr-1 did increase in response to both novel context exposure and to fear conditioning. These increases were not dependent upon state anxiety level. Finally, egr-1 increased in both the prelimbic and infralimbic areas of the medial prefrontal cortex following both novel context exposure and fear conditioning. However, in animals with low levels of state anxiety, the increase in egr-1 following fear conditioning was greater than that following context exposure.
The current series of experiments show that brain areas involved in fear and anxiety do not respond uniformly to novelty or to contextual fear conditioning. Activity in the amygdala was shown to be influenced by state anxiety level. However, activity in the hippocampus was not. Rather, the hippocampus appears to respond to novelty, likely as a contextual information processor. Finally, the medial prefrontal cortex seems to respond to novelty and fear conditioning as well. However, anxiety state may influence activity in the prefrontal cortex as well, possibly through connections with the amygdala. Overall, the current experiments show that brain areas active during states of fear are also active during states of anxiety when experiencing novelty. However, each area examined responded differently, indicating differential processing. Finally, the role of egr-1 is not confined to fear conditioning, but may also play a role in processing ambiguity.