A mitogen-activated protein kinase cascade in the CA1/CA2 subfield of the dorsal hippocampus is essential for long-term spatial memory.
Behavioral, biophysical, and pharmacological studies have implicated the hippocampus in the formation and storage of spatial memory. However, the molecular mechanisms underlying long-term spatial memory are poorly understood. In this study, we show that mitogen-activated protein kinase (MAPK, also called ERK) is activated in the dorsal, but not the ventral, hippocampus of rats after training in a spatial memory task, the Morris water maze. The activation was expressed as enhanced phosphorylation of MAPK in the pyramidal neurons of the CA1/CA2 subfield. In contrast, no increase in the percentage of phospho-MAPK-positive cells was detected in either the CA3 subfield or the dentate gyrus. The enhanced phosphorylation was observed only after multiple training trials but not after a single trial or after multiple trials in which the location of the target platform was randomly changed between each trial. Inhibition of the MAPK/ERK cascade in dorsal hippocampi did not impair acquisition, but blocked the formation of long-term spatial memory. In contrast, intrahippocampal infusion of SB203580, a specific inhibitor of the stress-activated MAPK (p38 MAPK), did not interfere with memory storage. These results demonstrate a MAPK-mediated cellular event in the CA1/CA2 subfields of the dorsal hippocampus that is critical for long-term spatial memory.
Blum
S
S
Department of Neurobiology and Anatomy, W. M. Keck Center for the Neurobiology of Learning and Memory, The University of Texas Medical School, Houston, Texas 77030, USA.
Moore
A N
AN
Adams
F
F
Dash
P K
PK
D000595:Amino Acid Sequence; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D018891:Dentate Gyrus / Q000502:physiology; D004791:Enzyme Inhibitors; D006624:Hippocampus / Q000502:physiology*; D007093:Imidazoles / Q000494:pharmacology; D007700:Kinetics; D018782:Maze Learning / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D017966:Pyramidal Cells / Q000201:enzymology / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D015398:Signal Transduction; D013028:Space Perception; D013379:Substrate Specificity; D048051:p38 Mitogen-Activated Protein Kinases
D004791:Enzyme Inhibitors; D007093:Imidazoles; D010455:Peptides; D011725:Pyridines; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580