Reciprocal patterns of c-fos expression in the medial prefrontal cortex and amygdala after extinction and renewal of conditioned fear in rats
Substantial evidence indicates that extinguished fear can be recovered after a change in experimental context (i.e., the renewal effect). The aim of this study was to characterize the neural circuitry underlying the retrieval of extinguished fear memories using c-Fos immunohistochemistry. Firstly, rats received auditory fear conditioning. Subsequently, they were extinguished by presenting CS-alone trials in either the same context as conditioning or in a second context. Then, all rats were tested for their fear of the auditory CS in the second context and sacrifi ced 90 min after testing. The presentation of the extinguished CS outside of the extinction context resulted in renewal of the freezing response relative to animals tested to the CS in the extinction context. In addition, the renewal of fear was associated with c-Fos expression in the prelimbic division of the medial prefrontal cortex, the lateral and basolateral nuclei of the amygdala, and the medial division of the central nucleus of the amygdala. In contrast, the presentation of the CS in the extinction context induced c-Fos expression in the infralimbic cortex, the intercalated nuclei of the amygdala and the dentate gyrus. Hippocampal areas CA1 and CA3 exhibited c-Fos expression when the CS was presented in either context. These data suggest that the context-specifi city of extinction may be mediated by prefrontal modulation of amygdala activity, and that the hippocampus may have a fundamental role in contextual memory retrieval.