Phosphorylated cAMP response element binding protein in the mouse brain after fear conditioning: relationship to Fos production

Phosphorylation of the cAMP response element binding protein (pCREB) trigge red by associative learning was monitored immunohistochemically in differen t areas of the mouse brain during a 6-h interval, starting immediately afte r training. One trial context-dependent fear conditioning was employed as a learning paradigm. Training consisted of contextual exposure followed by s hock. Control groups consisted of native mice, mice exposed to the context alone and mice exposed to an immediate shock in the context. For all traine d mice, the time course of CREB phosphorylation in hippocampus, parietal co rtex and amygdaloid nuclei exhibited a biphasic pattern. The early phase wa s between 0 and 30 min, and the late phase was between 3 and 6 It after tra ining. The animals exposed to context followed by an electric shock, as wel l as those exposed to an immediate electric shock, exhibited significantly higher pCREB levels than the mice subjected to context alone. During the la te phase, the pCREB levels were highest in the mice exposed to the context followed by shock, It was observed that CREB phosphorylation and Fos produc tion followed different regional and stimulus-dependent patterns. It is sug gested that the early phase of pCREB increase may be related to stress-rela ted behaviors, whereas the late phase may rather relate to memory consolida tion. (C) 2001 Elsevier Science BY All rights reserved.