TY - JOUR
T1 - CREB phosphorylation as a molecular marker of memory processing in the hippocampus for spatial learning
AU - Mizuno, Makoto
AU - Yamada, Kiyofumi
AU - Maekawa, Naoya
AU - Saito, Kuniaki
AU - Seishima, Mitsuru
AU - Nabeshima, Toshitaka
N1 - Funding Information:
This study was supported in part by a Grant-in-Aid for Scientific Research (No. 12670085), and Special Coordination Funds for Promoting Science and Technology, Target-oriented Brain Science Research Program, from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and an SRF Grant for Biomedical Research.
PY - 2002/7/18
Y1 - 2002/7/18
N2 - 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.
AB - 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.
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U2 - 10.1016/S0166-4328(01)00470-3
DO - 10.1016/S0166-4328(01)00470-3
M3 - Article
C2 - 12110446
AN - SCOPUS:0037130346
SN - 0166-4328
VL - 133
SP - 135
EP - 141
JO - Behavioural Brain Research
JF - Behavioural Brain Research
IS - 2
ER -