Inhibition of activity-dependent arc protein expression in the rat hippocampus impairs the maintenance of long-term potentiation and the consolidation of long-term memory

John F. Guzowski, Gregory L. Lyford, Gail D. Stevenson, Frank P. Houston, James L. McGaugh, Paul F Worley, Carol A. Barnes

Research output: Contribution to journalArticle

Abstract

It is widely believed that the brain processes information and stores memories by modifying and stabilizing synaptic connections between neurons. In experimental models of synaptic plasticity, such as long-term potentiation (LTP), the stabilization of changes in synaptic strength requires rapid de novo RNA and protein synthesis. Candidate genes, which could underlie activity-dependent plasticity, have been identified on the basis of their rapid induction in brain neurons. Immediate-early genes (IEGs) are induced in hippocampal neurons by high-frequency electrical stimulation that induces LTP and by behavioral training that results in long-term memory (LTM) formation. Here, we investigated the role of the IEG Arc (also termed Arg3.1) in hippocampal plasticity. Arc protein is known to be enriched in dendrites of hippocampal neurons where it associates with cytoskeletal proteins (Lyford et al., 1995). Arc is also notable in that its mRNA and protein accumulate in dendrites at sites of recent synaptic activity (Steward et al., 1998). We used intrahippocampal infusions of antisense oligodeoxynucleotides to inhibit Arc protein expression and examined the effect of this treatment on both LTP and spatial learning. Our studies show that disruption of Arc protein expression impairs the maintenance phase of LTP without affecting its induction and impairs consolidation of LTM for spatial water task training without affecting task acquisition or short-term memory. Thus, Arc appears to play a fundamental role in the stabilization of activity-dependent hippocampal plasticity.

Original languageEnglish (US)
Pages (from-to)3993-4001
Number of pages9
JournalJournal of Neuroscience
Volume20
Issue number11
StatePublished - Jun 1 2000

Fingerprint

Long-Term Memory
Long-Term Potentiation
Hippocampus
Neurons
Immediate-Early Genes
Dendrites
Proteins
Neuronal Plasticity
Cytoskeletal Proteins
Oligodeoxyribonucleotides
Brain
Short-Term Memory
Electric Stimulation
Theoretical Models
Maintenance
Inhibition (Psychology)
RNA
Messenger RNA
Water
Genes

Keywords

  • Gene
  • Hippocampus
  • Immediate-early
  • Long-term memory
  • Long-term potentiation
  • Neuron
  • Oligodeoxynucleotide
  • Spatial memory
  • Synaptic plasticity

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Inhibition of activity-dependent arc protein expression in the rat hippocampus impairs the maintenance of long-term potentiation and the consolidation of long-term memory. / Guzowski, John F.; Lyford, Gregory L.; Stevenson, Gail D.; Houston, Frank P.; McGaugh, James L.; Worley, Paul F; Barnes, Carol A.

In: Journal of Neuroscience, Vol. 20, No. 11, 01.06.2000, p. 3993-4001.

Research output: Contribution to journalArticle

Guzowski, John F. ; Lyford, Gregory L. ; Stevenson, Gail D. ; Houston, Frank P. ; McGaugh, James L. ; Worley, Paul F ; Barnes, Carol A. / Inhibition of activity-dependent arc protein expression in the rat hippocampus impairs the maintenance of long-term potentiation and the consolidation of long-term memory. In: Journal of Neuroscience. 2000 ; Vol. 20, No. 11. pp. 3993-4001.
@article{dbcb07b19f95432d816d37d04c27eeec,
title = "Inhibition of activity-dependent arc protein expression in the rat hippocampus impairs the maintenance of long-term potentiation and the consolidation of long-term memory",
abstract = "It is widely believed that the brain processes information and stores memories by modifying and stabilizing synaptic connections between neurons. In experimental models of synaptic plasticity, such as long-term potentiation (LTP), the stabilization of changes in synaptic strength requires rapid de novo RNA and protein synthesis. Candidate genes, which could underlie activity-dependent plasticity, have been identified on the basis of their rapid induction in brain neurons. Immediate-early genes (IEGs) are induced in hippocampal neurons by high-frequency electrical stimulation that induces LTP and by behavioral training that results in long-term memory (LTM) formation. Here, we investigated the role of the IEG Arc (also termed Arg3.1) in hippocampal plasticity. Arc protein is known to be enriched in dendrites of hippocampal neurons where it associates with cytoskeletal proteins (Lyford et al., 1995). Arc is also notable in that its mRNA and protein accumulate in dendrites at sites of recent synaptic activity (Steward et al., 1998). We used intrahippocampal infusions of antisense oligodeoxynucleotides to inhibit Arc protein expression and examined the effect of this treatment on both LTP and spatial learning. Our studies show that disruption of Arc protein expression impairs the maintenance phase of LTP without affecting its induction and impairs consolidation of LTM for spatial water task training without affecting task acquisition or short-term memory. Thus, Arc appears to play a fundamental role in the stabilization of activity-dependent hippocampal plasticity.",
keywords = "Gene, Hippocampus, Immediate-early, Long-term memory, Long-term potentiation, Neuron, Oligodeoxynucleotide, Spatial memory, Synaptic plasticity",
author = "Guzowski, {John F.} and Lyford, {Gregory L.} and Stevenson, {Gail D.} and Houston, {Frank P.} and McGaugh, {James L.} and Worley, {Paul F} and Barnes, {Carol A.}",
year = "2000",
month = "6",
day = "1",
language = "English (US)",
volume = "20",
pages = "3993--4001",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "11",

}

TY - JOUR

T1 - Inhibition of activity-dependent arc protein expression in the rat hippocampus impairs the maintenance of long-term potentiation and the consolidation of long-term memory

AU - Guzowski, John F.

AU - Lyford, Gregory L.

AU - Stevenson, Gail D.

AU - Houston, Frank P.

AU - McGaugh, James L.

AU - Worley, Paul F

AU - Barnes, Carol A.

PY - 2000/6/1

Y1 - 2000/6/1

N2 - It is widely believed that the brain processes information and stores memories by modifying and stabilizing synaptic connections between neurons. In experimental models of synaptic plasticity, such as long-term potentiation (LTP), the stabilization of changes in synaptic strength requires rapid de novo RNA and protein synthesis. Candidate genes, which could underlie activity-dependent plasticity, have been identified on the basis of their rapid induction in brain neurons. Immediate-early genes (IEGs) are induced in hippocampal neurons by high-frequency electrical stimulation that induces LTP and by behavioral training that results in long-term memory (LTM) formation. Here, we investigated the role of the IEG Arc (also termed Arg3.1) in hippocampal plasticity. Arc protein is known to be enriched in dendrites of hippocampal neurons where it associates with cytoskeletal proteins (Lyford et al., 1995). Arc is also notable in that its mRNA and protein accumulate in dendrites at sites of recent synaptic activity (Steward et al., 1998). We used intrahippocampal infusions of antisense oligodeoxynucleotides to inhibit Arc protein expression and examined the effect of this treatment on both LTP and spatial learning. Our studies show that disruption of Arc protein expression impairs the maintenance phase of LTP without affecting its induction and impairs consolidation of LTM for spatial water task training without affecting task acquisition or short-term memory. Thus, Arc appears to play a fundamental role in the stabilization of activity-dependent hippocampal plasticity.

AB - It is widely believed that the brain processes information and stores memories by modifying and stabilizing synaptic connections between neurons. In experimental models of synaptic plasticity, such as long-term potentiation (LTP), the stabilization of changes in synaptic strength requires rapid de novo RNA and protein synthesis. Candidate genes, which could underlie activity-dependent plasticity, have been identified on the basis of their rapid induction in brain neurons. Immediate-early genes (IEGs) are induced in hippocampal neurons by high-frequency electrical stimulation that induces LTP and by behavioral training that results in long-term memory (LTM) formation. Here, we investigated the role of the IEG Arc (also termed Arg3.1) in hippocampal plasticity. Arc protein is known to be enriched in dendrites of hippocampal neurons where it associates with cytoskeletal proteins (Lyford et al., 1995). Arc is also notable in that its mRNA and protein accumulate in dendrites at sites of recent synaptic activity (Steward et al., 1998). We used intrahippocampal infusions of antisense oligodeoxynucleotides to inhibit Arc protein expression and examined the effect of this treatment on both LTP and spatial learning. Our studies show that disruption of Arc protein expression impairs the maintenance phase of LTP without affecting its induction and impairs consolidation of LTM for spatial water task training without affecting task acquisition or short-term memory. Thus, Arc appears to play a fundamental role in the stabilization of activity-dependent hippocampal plasticity.

KW - Gene

KW - Hippocampus

KW - Immediate-early

KW - Long-term memory

KW - Long-term potentiation

KW - Neuron

KW - Oligodeoxynucleotide

KW - Spatial memory

KW - Synaptic plasticity

UR - http://www.scopus.com/inward/record.url?scp=0034213297&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034213297&partnerID=8YFLogxK

M3 - Article

C2 - 10818134

AN - SCOPUS:0034213297

VL - 20

SP - 3993

EP - 4001

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 11

ER -