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Sequestration of serum response factor in the hippocampus impairs long‐term spatial memory
Author(s) -
Dash Pramod K.,
Orsi Sara A.,
Moore Anthony N.
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2004.03016.x
Subject(s) - decoy , long term memory , mapk/erk pathway , hippocampus , kinase , hippocampal formation , oligonucleotide , transcription factor , biology , protein kinase a , microbiology and biotechnology , neuroscience , genetics , gene , receptor , cognition
The formation of long‐term memory has been shown to require protein kinase‐mediated gene expression. One such kinase, mitogen‐activated protein kinase/extracellular signal‐regulated kinase (MAPK/ERK), can lead to the phosphorylation of serum response factor (SRF) and Elk‐1, enhancing the expression of target genes. However, a direct involvement of these transcription factors in memory storage has not been demonstrated. We have employed an oligonucleotide decoy technique to interrogate SRF and Elk‐1. Previously, it has been shown that intra‐amygdalal infusion of small double‐stranded decoy oligonucleotides for nuclear factor‐kappaB (NFkappaB) can impair long‐term memory for fear‐potentiated startle. Using this approach, we found that intra‐hippocampal infusion of NFkappaB decoy oligonucleotides also impairs long‐term spatial memory, consistent with a role for this factor in long‐term memory storage. Decoy oligonucleotides containing the binding site for SRF, as confirmed by shift‐western, did not influence memory acquisition but impaired long‐term spatial memory. Analysis of search behavior during the transfer test revealed deficits consistent with a loss of precise platform location information. In contrast, oligonucleotides with a binding site for either Elk‐1 or another target of ERK activity, SMAD3/SMAD4, did not interfere with memory formation or storage. These findings suggest that SRF‐mediated gene expression is required for long‐term spatial memory.