An Intrinsic Transcriptional Program Underlying Synaptic Scaling during Activity Suppression

Katie Schaukowitch, Austin L. Reese, Seung Kyoon Kim, Gokhul Kilaru, Jae Yeol Joo, Ege T. Kavalali, Tae Kyung Kim

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1512-1526
Number of pages15
JournalCell Reports
Volume18
Issue number6
DOIs
StatePublished - Feb 7 2017

Keywords

  • enhancer
  • homeostatic scaling
  • Nptx1
  • T-VGCC
  • transcription

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Schaukowitch, K., Reese, A. L., Kim, S. K., Kilaru, G., Joo, J. Y., Kavalali, E. T., & Kim, T. K. (2017). An Intrinsic Transcriptional Program Underlying Synaptic Scaling during Activity Suppression. Cell Reports, 18(6), 1512-1526. https://doi.org/10.1016/j.celrep.2017.01.033