Fornix-dependent induction of hippocampal CCAAT enhancer-binding protein beta and delta co-localizes with phosphorylated cAMP response element-binding protein and accompanies long-term memory consolidation

The cAMP response element-binding protein (CREB) is an evolutionarily conse rved transcription regulator essential for longterm memory formation. It is not known, however, whether the molecular events downstream of CREB activa tion are also conserved. An early, cAMP-dependent event necessary for learn ing-related long-term synaptic plasticity in the invertebrate Aplysia calif ornica is the induction of the transcription factor CCAAT enhancer-binding protein (C/EBP). Here we show that two homologs in the rat, C/EBP beta and C/EBP delta, are induced at discrete times after inhibitory avoidance learn ing and colocalize with phosphorylated CREB in the hippocampus. This induct ion is blocked by fornix lesions, which are known to disrupt activation of CREB in the hippocampus and to impair memory consolidation. These results i ndicate that C/EBPs are evolutionarily conserved components of the CREB-dep endent gene cascade activated in long-term memory.