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
| Autor: | Gregory L. Lyford, Frank P. Houston, Carol A. Barnes, Paul F. Worley, Gail D. Stevenson, John F. Guzowski, James L. McGaugh |
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| Rok vydání: | 2000 |
| Předmět: |
Male
Blotting Western Long-Term Potentiation Nonsynaptic plasticity Nerve Tissue Proteins Hippocampal formation Biology Hippocampus Oligodeoxyribonucleotides Antisense Memory Metaplasticity Animals ARTICLE Maze Learning Neuronal memory allocation Neuronal Plasticity Arc (protein) Behavior Animal General Neuroscience Long-term potentiation Rats Inbred F344 Rats Electrophysiology Cytoskeletal Proteins Gene Expression Regulation Synapses Synaptic plasticity Memory consolidation Neuroscience |
| Zdroj: | The Journal of Neuroscience. 20:3993-4001 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.20-11-03993.2000 |
| Popis: | 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 rapidde novoRNA 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 IEGArc(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).Arcis 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,Arcappears to play a fundamental role in the stabilization of activity-dependent hippocampal plasticity. |
| Databáze: | OpenAIRE |
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