Cell Reports
Volume 18, Issue 6, 7 February 2017, Pages 1512-1526
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Article
An Intrinsic Transcriptional Program Underlying Synaptic Scaling during Activity Suppression

https://doi.org/10.1016/j.celrep.2017.01.033Get rights and content
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Highlights

  • A transcription program is activated by TTX-mediated activity suppression

  • Upregulated gene products functionally contribute to synaptic upscaling

  • T-type calcium channel activity is required for transcriptional activation

  • Transcriptional induction also occurs in an in vivo context

Summary

Homeostatic scaling allows neurons to maintain stable activity patterns by globally altering their synaptic strength in response to changing activity levels. Suppression of activity by the blocking of action potentials increases synaptic strength through an upregulation of surface α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. Although this synaptic upscaling was shown to require transcription, the molecular nature of the intrinsic transcription program underlying this process and its functional significance have been unclear. Using RNA-seq, we identified 73 genes that were specifically upregulated in response to activity suppression. In particular, Neuronal pentraxin-1 (Nptx1) increased within 6 hr of activity blockade, and knockdown of this gene blocked the increase in synaptic strength. Nptx1 induction is mediated by calcium influx through the T-type voltage-gated calcium channel, as well as two transcription factors, SRF and ELK1. Altogether, these results uncover a transcriptional program that specifically operates when neuronal activity is suppressed to globally coordinate the increase in synaptic strength.

Keywords

homeostatic scaling
transcription
Nptx1
T-VGCC
enhancer

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Present address: Department of Neural Development and Disease, Korea Brain Research Institute, Daegu 41068, Korea

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