title: Sequestration of serum response factor in the hippocampus impairs long-term spatial memory.
abstract: 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.
authors.affiliation: The Vivian L. Smith Center for Neurologic Research, Department of Neurobiology and Anatomy, The University of Texas Medical School, Houston, Texas 77225, USA. p.dash@uth.tmc.edu
authors.forename: Pramod K
authors.initials: PK
authors.lastname: Dash
authors.forename: Sara A
authors.initials: SA
authors.lastname: Orsi
authors.forename: Anthony N
authors.initials: AN
authors.lastname: Moore
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D008569:Memory Disorders / Q000378:metabolism*; D016328:NF-kappa B / Q000008:administration & dosage / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D026362:Serum Response Factor / Q000378:metabolism*; D013037:Spatial Behavior / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
chemical_list: D016328:NF-kappa B; D026362:Serum Response Factor