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

Brain Res Mol Brain Res. 2001 Oct 19;94(1-2):15-24. doi: 10.1016/s0169-328x(01)00174-7.


Phosphorylation of the cAMP response element binding protein (pCREB) triggered by associative learning was monitored immunohistochemically in different areas of the mouse brain during a 6-h interval, starting immediately after training. One trial context-dependent fear conditioning was employed as a learning paradigm. Training consisted of contextual exposure followed by shock. Control groups consisted of naïve mice, mice exposed to the context alone and mice exposed to an immediate shock in the context. For all trained mice, the time course of CREB phosphorylation in hippocampus, parietal cortex and amygdaloid nuclei exhibited a biphasic pattern. The early phase was between 0 and 30 min, and the late phase was between 3 and 6 h after training. The animals exposed to context followed by an electric shock, as well as those exposed to an immediate electric shock, exhibited significantly higher pCREB levels than the mice subjected to context alone. During the late phase, the pCREB levels were highest in the mice exposed to the context followed by shock. It was observed that CREB phosphorylation and Fos production followed different regional and stimulus-dependent patterns. It is suggested that the early phase of pCREB increase may be related to stress-related behaviors, whereas the late phase may rather relate to memory consolidation.

MeSH terms

  • Amygdala / physiology
  • Animals
  • Association Learning / physiology
  • Brain Chemistry / physiology*
  • Conditioning, Psychological / physiology
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Dentate Gyrus / physiology
  • Electroconvulsive Therapy
  • Fear / physiology*
  • Male
  • Memory / physiology
  • Mice
  • Mice, Inbred C57BL
  • Parietal Lobe / physiology
  • Phosphorylation
  • Proto-Oncogene Proteins c-fos / analysis
  • Proto-Oncogene Proteins c-fos / biosynthesis*


  • Cyclic AMP Response Element-Binding Protein
  • Proto-Oncogene Proteins c-fos