Synaptic activation causes the mRNA for the IEG Arc to localize selectively near activated postsynaptic sites on
O Steward1, C S Wallace, G L Lyford
1Department of Neuroscience, University of Virginia, Charlottesville 22908, USA. os@virginia.edu
Abstract:
Polyribosomal complexes beneath postsynaptic sites on dendrites provide a substrate for local translation of particular mRNAs, but the signals that target mRNAs to synapses remain to be defined. Here, we report 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. Newly synthesized Arc protein also accumulates in the portion of the dendrite that had been synaptically activated. The targeting of Arc mRNA was not disrupted by locally inhibiting protein synthesis, indicating that the signals for mRNA localization reside in the mRNA itself. This novel mechanism through which newly synthesized mRNA is precisely targeted to activated synapses is well suited to play a role in the enduring forms of activity-dependent synaptic modification that require protein synthesis.
Insights
Newly synthesized Arc messenger RNA (mRNA) precisely targets activated synapses in the brain. This localization mechanism is crucial for activity-dependent synaptic plasticity, even when protein synthesis is inhibited.
Area of Science:
- Neuroscience
- Molecular Biology
- Synaptic Plasticity
Background:
- Polyribosomes at postsynaptic sites enable local mRNA translation.
- Signals for mRNA targeting to synapses are not fully understood.
Purpose of the Study:
- To investigate the targeting signals for mRNA localization to activated synapses.
- To elucidate the mechanism of activity-dependent mRNA transport.
Main Methods:
- High-frequency activation of perforant path projections.
- Selective mRNA and protein detection in activated dendritic segments.
Main Results:
- Newly synthesized immediate-early gene (IEG) Arc mRNA selectively localized to activated dendritic segments.
- Arc protein accumulated in synaptically activated areas.
- mRNA targeting persisted despite local protein synthesis inhibition.
Conclusions:
- Arc mRNA contains intrinsic signals for synaptic targeting.
- This mechanism facilitates local protein synthesis for synaptic modification.
- Activity-dependent mRNA localization plays a key role in enduring synaptic plasticity.
Related Concept Videos
Synaptic Signaling
Synaptic Signaling
Most synapses are chemical, meaning an electrical impulse or action potential spurs the release of chemical messengers called neurotransmitters. The neuron sending the signal is called the presynaptic neuron, and the neuron receiving the signal is the postsynaptic neuron.
The presynaptic neuron fires an action potential that...
Excitatory and Inhibitory Effects of Neurotransmitters
Chemical Synapses
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
Ligand-Gated Ion Channel Receptor: Gating Mechanism
Chemical Synapses
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...


