Expressions of CCAAT/Enhancer-binding proteins beta and delta and their activities are intensified by cAMP signaling as well as Ca2+/calmodulin kinases activation in hippocampal neurons.

The transcription factor, Aplysia CCAAT enhancer-binding protein (ApC/EBP), plays a crucial role in long term facilitation, a synaptic mechanism of long term memory in Aplysia. To gain a clue to whether the mammalian C/EBP family of transcription factors are also involved in long term memory, we examined how C/EBP activities in hippocampal neurons can be modulated in response to cAMP and Ca2+, crucial inductive signals for memory formation. As a result, stimulation of either cAMP or Ca2+ signals in hippocampal neurons was found to enhance mRNA expressions and DNA binding activities of C/EBPbeta and C/EBPdelta. Furthermore, it is indicated that CaM kinases have essential roles for increasing the expression and DNA binding activities of C/EBPbeta in hippocampal neurons activated by membrane depolarization. Overexpression of constitutively active calcium/calmodulin-dependent kinase IV was found to directly stimulate either C/EBPbeta-dependent or C/EBPdelta-dependent transcription, reinforcing the evidence that C/EBP family members contribute to Ca2+-dependent transcription. Thus, these results suggest that C/EBPbeta and C/EBPdelta may be involved in the transcription-dependent phase of memory formation by increasing the expression of both the DNA binding and the transcriptional activities under the direction of cAMP and/or Ca2+ signaling in hippocampal neurons.