Cellular imaging with zif268 expression in the rat nucleus accumbens and frontal cortex further dissociates the neural pathways activated following the retrieval of contextual and cued fear memory.

Quantitative in situ hybridization revealed that the expression of the plasticity-associated gene zif268 was increased in specific regions of the rat frontal cortex and nucleus accumbens following fear memory retrieval. Increased expression of zif268 was observed in neurons in the core of the nucleus accumbens during the retrieval of contextual and discrete cued fear associations. In contrast, zif268 expression was additionally induced in neurons of the nucleus accumbens shell and the anterior cingulate cortex during the retrieval of contextual but not cued fear memories. No changes in the expression of this gene were seen in the ventral medial prefrontal cortex or ventral and lateral regions of the orbitofrontal cortex that were correlated specifically with the retrieval of fear memory. These experiments demonstrate the specific and dissociable activation of limbic cortical-ventral striatal regions that accompanies cued and contextual fear. These data, together with those previously published by our laboratory (Hall, J., Thomas, K.L. & Everitt, B.J. (2001) J. Neurosci., 21, 2186-2193), suggest that retrieval of contextual fear memories activates a wider limbic cortical-ventral striatal neural circuitry than does retrieval of cued fear memories. Moreover, the expression of zif268 may contribute to plasticity and reconsolidation of fear memory in these dissociable pathways.