An Intrinsic Transcriptional Program Underlying Synaptic Scaling during Activity Suppression

Publication date: 7 February 2017
Source:Cell Reports, Volume 18, Issue 6
Author(s): Katie Schaukowitch, Austin L. Reese, Seung-Kyoon Kim, Gokhul Kilaru, Jae-Yeol Joo, Ege T. Kavalali, Tae-Kyung Kim
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.

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Teaser

Schaukowitch et al. demonstrate that an intrinsic transcriptional program in neurons underlies the homeostatic plasticity induced in response to chronic activity suppression. Calcium-dependent signaling through the T-type calcium channel is critical for transcriptional activation and synaptic upscaling in cultured neurons.


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