Abstract
Newly synthesized Arc mRNA is selectively targeted to synapses that have experienced particular patterns of activity. Here, we demonstrate that the targeting requires NMDA receptor activation. Arc expression was induced by an electroconvulsive seizure, and the newly synthesized mRNA was then targeted to synaptic sites by activating the perforant path projections to the dentate gyrus. When micropipette electrodes containing NMDA receptor antagonists (MK801 or APV) were positioned in the dentate gyrus during the stimulation period, newly synthesized Arc mRNA was transported into dendrites but did not localize in the activated lamina; instead, the mRNA remained diffusely distributed. AMPA receptor antagonists (CNQX) blocked targeting of Arc mRNA in a small region, and mGluR antagonists (MCPG) did not affect localization. These results demonstrate that NMDA receptor activation is required for the targeting of Arc mRNA to active synapses.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Compartmentation / physiology
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Cytoskeletal Proteins / drug effects
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Cytoskeletal Proteins / genetics*
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Cytoskeletal Proteins / metabolism
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Dendrites / drug effects
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Dendrites / metabolism*
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Dendrites / ultrastructure
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Dentate Gyrus / cytology
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Dentate Gyrus / drug effects
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Dentate Gyrus / metabolism*
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Electroshock / adverse effects
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Excitatory Amino Acid Antagonists / pharmacology
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Male
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Nerve Tissue Proteins / drug effects
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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 / physiology
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Perforant Pathway / cytology
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Perforant Pathway / drug effects
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Perforant Pathway / metabolism
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RNA, Messenger / biosynthesis*
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RNA, Messenger / drug effects
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Rats
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Rats, Sprague-Dawley
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Receptors, AMPA / antagonists & inhibitors
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Receptors, AMPA / metabolism
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Receptors, Metabotropic Glutamate / antagonists & inhibitors
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Receptors, Metabotropic Glutamate / metabolism
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Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
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Receptors, N-Methyl-D-Aspartate / metabolism*
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Synapses / drug effects
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Synapses / metabolism*
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Synapses / ultrastructure
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology*
Substances
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Cytoskeletal Proteins
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Excitatory Amino Acid Antagonists
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Nerve Tissue Proteins
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RNA, Messenger
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Receptors, AMPA
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Receptors, Metabotropic Glutamate
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Receptors, N-Methyl-D-Aspartate
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activity regulated cytoskeletal-associated protein