Selective Targeting of Newly Synthesized Arc mRNA to Active Synapses Requires NMDA Receptor Activation

@article{Steward2001SelectiveTO,
  title={Selective Targeting of Newly Synthesized Arc mRNA to Active Synapses Requires NMDA Receptor Activation},
  author={Oswald Steward and Paul F Worley},
  journal={Neuron},
  year={2001},
  volume={30},
  pages={227-240}
}
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… 
Selective Localization of Arc mRNA in Dendrites Involves Activity- and Translation-Dependent mRNA Degradation
TLDR
In vivo in rats that newly synthesized Arc mRNA accumulates at activated synapses and that synaptic activity simultaneously triggers mRNA decay that eliminates Arc mRNA from inactive dendritic domains are shown, revealing a novel mechanism for controlling mRNA distribution within dendrites.
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TLDR
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Arc mRNA dynamics: Return to sender – the NMDA receptor provides the targeting address for Arc mRNA
  • K. Martin
  • Biology, Medicine
    Trends in Neurosciences
  • 2001
TLDR
This work has shown that the mRNA encoded by the immediate-early gene Arc is not only transported into dendrites, but localizes specifically to activated postsynaptic sites, which has now been shown to depend on local signaling through the NMDA receptor.
Actin Polymerization and ERK Phosphorylation Are Required for Arc/Arg3.1 mRNA Targeting to Activated Synaptic Sites on Dendrites
TLDR
The results indicate that the reorganization of the actin cytoskeletal network in conjunction with MAP kinase activation is required for targeting newly synthesized Arc/Arg3.1 mRNA localization.
Spatial Exploration-Induced Arc mRNA and Protein Expression: Evidence for Selective, Network-Specific Reactivation
TLDR
This is the first demonstration of network-selective translational events consequent to spatial behavior and suggests a role for immediate-early genes in circuit-specific, late-phase synaptic biology.
4.29 – Dendritic Transport of mRNA, the IEG Arc, and Synaptic Modifications Involved in Memory Consolidation
TLDR
Findings support a model in which Arc acts to maintain synaptic homeostasis in the presence of synaptic potentiation, and provide a testable framework for understanding LTM storage at the cellular level.
Role of Action Potentials in Regulating Gene Transcription: Relevance to LTP
The late phase of Long Term Potentiation (LTP) appears to require transcription, but how the nucleus is informed remains unknown. We propose that calcium elevation from multiple action potentials
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References

SHOWING 1-10 OF 12 REFERENCES
Synaptic Activation Causes the mRNA for the IEG Arc to Localize Selectively near Activated Postsynaptic Sites on Dendrites
TLDR
It is reported that high frequency activation of the perforant path projections to the dentate gyrus causes newly synthesized mRNA for the immediate-early gene (IEG) Arc to localize selectively in activated dendritic segments.
Somatodendritic expression of an immediate early gene is regulated by synaptic activity.
TLDR
The entire nucleotide sequence of the cDNA is reported, which encodes an open reading frame of 396 amino acids and offers the potential for local synthesis of the protein at activated postsynaptic sites and may underlie synapse-specific modifications during long-term plastic events.
Synapse-Specific, Long-Term Facilitation of Aplysia Sensory to Motor Synapses: A Function for Local Protein Synthesis in Memory Storage
TLDR
By perfusing serotonin onto the synapses made onto one motor neuron, it is found that a single axonal branch can undergo long-term branch-specific facilitation, which depends on CREB-mediated transcription and involves the growth of new synaptic connections exclusively at the treated branch.
Blockade of inhibition in a pathway with dual excitatory and inhibitory action unmasks a capability for LTP that is otherwise not expressed
TLDR
Results suggest that LTP is not normally expressed by the dentate commissural pathway because the simultaneous inhibition prevents the depolarization-related relief of Mg2+ blockade of the NMDA receptor.
Differential Intracellular Sorting of Immediate Early Gene mRNAs Depends on Signals in the mRNA Sequence
This study characterizes the differential targeting of recently synthesized immediate early gene (IEG) mRNAs to neuronal cell bodies versus dendrites and tests the hypothesis that this targeting is
Synapses as associative memory elements in the hippocampal formation
TLDR
Paired conditioning of ipsi- and contralateral inputs by nearly simultaneous conditioning stimulation of the EC bilaterally results in LTP in the crossing system, and this associatively induced LTP of the crossed system can be reversed by subsequent conditioning of the ipsilateral system alone.
Arc, a growth factor and activity-regulated gene, encodes a novel cytoskeleton-associated protein that is enriched in neuronal dendrites
TLDR
Analysis of the deduced amino acid sequence indicates a region of homology with alpha-spectrin, and observations suggest that Arc may play a role in activity-dependent plasticity of dendrites.
Synaptic tagging and long-term potentiation
TLDR
It is shown that weak tetanic stimulation, which ordinarily leads only to early LTP, or repeated tetanization in the presence of protein-Synthesis inhibitors, each results in protein-synthesis-dependent late LTP; this indicates that the persistence of LTP depends not only on local events during its induction, but also on the prior activity of the neuron.
A Macromolecular Synthesis-Dependent Late Phase of Long-Term Potentiation Requiring cAMP in the Medial Perforant Pathway of Rat Hippocampal Slices
TLDR
It is found that both a short-lasting and a long-lasting potentiation (L-LTP) can be induced in the MPP of rat hippocampal slices by applying repeated tetanization in reduced levels of magnesium.
A Requirement for Local Protein Synthesis in Neurotrophin-Induced Hippocampal Synaptic Plasticity
TLDR
Two neurotrophic factors, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), are able to produce a long-lasting enhancement of synaptic transmission in the hippocampus, allowing synapses to exert local control over the complement of proteins expressed at individual synaptic sites.
...
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