Interactions of the dorsal hippocampus, medial prefrontal cortex and nucleus accumbens in formation of fear memory: Difference in inhibitory avoidance learning and contextual fear conditioning

Abstract

Learning active or reactive responses to fear involves different brain circuitry. This study examined how the nuclus accumbens (NAc), dorsal hippocampus (DH) and medial prefrontal cortex (mPFC) may interact in memory processing for these two kinds of responses. Male Wistar rats with cannulae implanted in these areas were trained on a contextual fear conditioning or inhibitory avoidance task that respectively engaged a reactive or active response to fear in the test. Immediately after training, a memory modulating factor released by stress, norepinephrine (NE), was infused into one region and 4% lidocaine into another to examine if an upstream activation effect could be blocked by the downstream suppression. Retention tested 1day later showed that in both tasks posttraining infusion of NE at different doses into either the DH or mPFC enhanced retention but the enhancement was blocked by concurrent infusion of lidocaine into the other region, suggesting reliance of the effect on functional integrity of both regions. Further, posttraining intra-NAc lidocaine infusion attenuated memory enhancement of NE infused to the DH or mPFC in the inhibitory avoidance task but did not do so in contextual fear conditioning. These results suggest that NE regulation of memory formation for the reactive and active responses to fear may rely on distinct interactions among the DH, mPFC and NAc.