CREB phosphorylation as a molecular marker of memory processing in the hippocampus for spatial learning

Makoto Mizuno, Kiyofumi Yamada, Naoya Maekawa, Kuniaki Saito, Mitsuru Seishima, Toshitaka Nabeshima

Research output: Contribution to journalArticlepeer-review

194 Citations (Scopus)


Regulation of gene transcription via the cyclic adenosine 3′,5′-monophosphate (cAMP)-mediated second messenger pathway has been implicated in learning and memory. Although the cAMP response element-binding protein (CREB) is an important transcription factor involved in long-term memory, it remains to be determined whether the CREB-dependent events are attributed to spatial learning and memory in a radial arm maze. Here we demonstrate that cAMP-dependent protein kinase A (PKA) and CREB are activated in the course of spatial learning. The radial maze training in rats resulted in a significant increase in PKA and CREB phosphorylation in the hippocampus in the course of spatial learning, which was followed by spatial memory formation. On the other hand, neither the phosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and extracellular signal-regulated kinase (ERK) nor the mRNA level of brain-derived neurotrophic factor was significantly affected. These results suggest that activation of the PKA/CREB signaling pathway in the hippocampus plays an important role in spatial memory formation.

Original languageEnglish
Pages (from-to)135-141
Number of pages7
JournalBehavioural Brain Research
Issue number2
Publication statusPublished - 18-07-2002
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Behavioral Neuroscience


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