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Published on: September 26, 2015
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DNA methylation regulates neuronal glutamatergic synaptic scaling
Jarrod P Meadows1, Mikael C Guzman-Karlsson1, Scott Phillips1
1Evelyn F. McKnight Brain Institute, Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Science Signaling
|June 25, 2015
Summary
DNA demethylation enhances neuronal communication by upscaling synapses, crucial for memory formation. This epigenetic process regulates gene expression, impacting synaptic strength and long-term memory storage in the brain.
Area of Science:
- Neuroscience
- Epigenetics
- Molecular Biology
Background:
- Cell-wide synaptic upscaling enhances neuronal receptiveness at glutamatergic synapses.
- Synaptic plasticity and epigenetic mechanisms are potentially involved in long-term memory storage within cortical circuits.
Purpose of the Study:
- To investigate the role of DNA cytosine demethylation in mediating synaptic upscaling.
- To explore the contribution of epigenetic modifications to synaptic plasticity and memory formation.
Main Methods:
- Cultured cortical neurons were treated with tetrodotoxin (TTX) to inhibit neuronal activity.
- DNA methyltransferase (DNMT) activity was inhibited using the small-molecule inhibitor RG108 or by gene knockdown.
- The effect of inhibiting the cytosine demethylase TET1 on synaptic upscaling was examined.
Main Results:
- DNA cytosine demethylation was found to mediate multiplicative synaptic upscaling of glutamatergic synaptic strength.
- Inhibiting neuronal activity or DNMTs increased gene expression for glutamate receptors and trafficking proteins, leading to synaptic upscaling.
- DNMT inhibition-induced upscaling was transcription-dependent and blocked by TET1 knockdown, indicating a role for DNA methylation dynamics.
Conclusions:
- DNA methylation status regulates transcription-dependent glutamatergic synaptic homeostasis.
- Covalent DNA modifications, specifically demethylation, contribute to synaptic plasticity underlying memory formation and stabilization.
