Abstract
Learning and memory depend critically on long-term synaptic plasticity, which requires neuronal gene expression. In the prevailing view, AMPA receptors mediate fast excitatory synaptic transmission and effect short-term plasticity, but they do not directly regulate neuronal gene expression. By studying regulation of Arc, a gene required for long-term plasticity, we uncovered a new role for AMPA receptors in neuronal gene expression. Spontaneous synaptic activity or activity induced by brain-derived neurotrophic factor (BDNF) elicited Arc expression in cultures of rat cortical neurons and in organotypic brain slices. Notably, inhibiting AMPA receptors strongly potentiated activity-dependent Arc expression. We found that AMPA receptors negatively regulate Arc transcription, but not translation or stability, through a mechanism involving a pertussis toxin-sensitive G protein. These results provide insights into the activity-dependent mechanisms of Arc expression and suggest that, in addition to effecting short-term plasticity, AMPA receptors regulate genes involved in long-term plasticity.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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Bicuculline / pharmacology
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Blotting, Northern / methods
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Blotting, Western / methods
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Brain-Derived Neurotrophic Factor / pharmacology
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Calcium / metabolism
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Cells, Cultured
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Cerebral Cortex / cytology
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / metabolism*
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Drug Interactions
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Enzyme Inhibitors / pharmacology
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Excitatory Amino Acid Antagonists / pharmacology
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GABA Antagonists / pharmacology
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Gene Expression / drug effects
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Gene Expression / physiology*
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Immunohistochemistry / methods
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In Situ Hybridization / methods
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In Vitro Techniques
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Neuronal Plasticity / drug effects
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Neuronal Plasticity / genetics*
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Neurons / drug effects
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Neurons / physiology
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Rats
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Receptors, AMPA / physiology*
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Transfection / methods
Substances
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Brain-Derived Neurotrophic Factor
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Cytoskeletal Proteins
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Enzyme Inhibitors
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Excitatory Amino Acid Antagonists
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GABA Antagonists
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Nerve Tissue Proteins
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Receptors, AMPA
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activity regulated cytoskeletal-associated protein
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Calcium
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Bicuculline