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REST-Dependent Presynaptic Homeostasis Induced by Chronic Neuronal Hyperactivity.
F Pecoraro-Bisogni1,2, Gabriele Lignani3,4, A Contestabile2
1Department of Experimental Medicine, Section of Physiology, University of Genova, Viale Benedetto XV 3, 16132, Genoa, Italy.
Molecular Neurobiology
|August 9, 2017
Summary
The study reveals that REST, a transcriptional repressor, downscales both neuronal intrinsic excitability and presynaptic efficiency. This molecular player is crucial for neuronal homeostasis during chronic hyperactivity.
Area of Science:
- Neuroscience
- Molecular Biology
- Cellular Biology
Background:
- Homeostatic plasticity balances neuronal activity through synaptic strength or intrinsic excitability adjustments.
- A unified molecular model for these distinct homeostatic processes is currently lacking.
- REST was previously identified as critical for downscaling intrinsic excitability in response to hyperactivity.
Purpose of the Study:
- To investigate REST's role in synaptic homeostasis.
- To determine if REST influences synaptic strength during neuronal hyperactivity.
- To elucidate the molecular mechanisms underlying REST-mediated synaptic plasticity.
Main Methods:
- Utilized cultured hippocampal neurons subjected to prolonged elevated electrical activity.
- Investigated REST's effect on excitatory synapse strength.
- Analyzed changes in synaptic vesicle pool size.
- Examined transcriptional and translational regulation of presynaptic REST target genes.
Main Results:
- REST reduces excitatory synapse strength at the presynaptic level.
- Chronic hyperactivity leads to a REST-dependent decrease in synaptic vesicle pool size.
- This decrease is mediated by transcriptional and translational repression of presynaptic REST target genes.
Conclusions:
- REST is a key molecular player in neuronal homeostasis.
- REST simultaneously downscales intrinsic excitability and presynaptic efficiency in response to hyperactivity.
- REST mediates activity-dependent transcriptional regulation of homeostatic plasticity.
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