CREB phosphorylation as a molecular marker of memory processing in the hippocampus for spatial learning.
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.
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Japan.
Makoto
M
Mizuno
Kiyofumi
K
Yamada
Naoya
N
Maekawa
Kuniaki
K
Saito
Mitsuru
M
Seishima
Toshitaka
T
Nabeshima
D000818:Animals; D015415:Biomarkers; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism* / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013028:Space Perception / Q000502:physiology
D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D017868:Cyclic AMP-Dependent Protein Kinases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases