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

7 Citations (Scopus)

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

Fingerprint

Transcription
Genes
Serum Response Factor
Gene Knockdown Techniques
AMPA Receptors
Calcium Channels
Action Potentials
Neurons
RNA
Calcium
Acids
Electric potential
neuronal pentraxin

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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

An Intrinsic Transcriptional Program Underlying Synaptic Scaling during Activity Suppression. / Schaukowitch, Katie; Reese, Austin L.; Kim, Seung Kyoon; Kilaru, Gokhul; Joo, Jae Yeol; Kavalali, Ege T.; Kim, Tae Kyung.

In: Cell Reports, Vol. 18, No. 6, 07.02.2017, p. 1512-1526.

Research output: Contribution to journalArticle

Schaukowitch, K, Reese, AL, Kim, SK, Kilaru, G, Joo, JY, Kavalali, ET & Kim, TK 2017, 'An Intrinsic Transcriptional Program Underlying Synaptic Scaling during Activity Suppression', Cell Reports, vol. 18, no. 6, pp. 1512-1526. https://doi.org/10.1016/j.celrep.2017.01.033
Schaukowitch K, Reese AL, Kim SK, Kilaru G, Joo JY, Kavalali ET et al. An Intrinsic Transcriptional Program Underlying Synaptic Scaling during Activity Suppression. Cell Reports. 2017 Feb 7;18(6):1512-1526. https://doi.org/10.1016/j.celrep.2017.01.033
Schaukowitch, Katie ; Reese, Austin L. ; Kim, Seung Kyoon ; Kilaru, Gokhul ; Joo, Jae Yeol ; Kavalali, Ege T. ; Kim, Tae Kyung. / An Intrinsic Transcriptional Program Underlying Synaptic Scaling during Activity Suppression. In: Cell Reports. 2017 ; Vol. 18, No. 6. pp. 1512-1526.
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