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PMID: 10212313 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

A mitogen-activated protein kinase cascade in the CA1/CA2 subfield of the dorsal hippocampus is essential for long-term spatial memory.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 19 ·No. 9 ·1999-05-01 ·Pages 3535-44

Blum S, Moore AN, Adams F, Dash PK

Abstract

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.

MeSH Terms
Amino Acid Sequence Animals Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors,metabolism Cyclic AMP-Dependent Protein Kinases/metabolism Dentate Gyrus/physiology Enzyme Inhibitors Hippocampus/physiology Imidazoles/pharmacology Kinetics Maze Learning/physiology Memory/physiology Mitogen-Activated Protein Kinase 1/metabolism Mitogen-Activated Protein Kinases Molecular Sequence Data Peptides/chemistry,metabolism Phosphorylation Protein Kinase C/metabolism Pyramidal Cells/enzymology,physiology Pyridines/pharmacology Rats Rats, Long-Evans Signal Transduction Space Perception Substrate Specificity p38 Mitogen-Activated Protein Kinases
Chemicals
Enzyme Inhibitors Imidazoles Peptides Pyridines Cyclic AMP-Dependent Protein Kinases Protein Kinase C Calcium-Calmodulin-Dependent Protein Kinases Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinases p38 Mitogen-Activated Protein Kinases SB 203580
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Blum 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
Adams F
Dash P K
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
0270-6474
Published
1999-05-01
Pages
3535-44
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6782236
Subset
IM
Grants
NINDS NIH HHS · R01 NS035457 · United States
NIMH NIH HHS · MH49662 · United States
NINDS NIH HHS · NS35457 · United States
External Links
PubMed source PMC Full Text View journal details
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