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| Status |
Public on Feb 07, 2017 |
| Title |
An intrinsic transcriptional program underlying synaptic scaling during activity suppression |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| 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 blocking action potentials increases synaptic strength through an upregulation of surface AMPA receptors. Although this synaptic up-scaling 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 h of activity blockade, and knockdown of this gene blocked the increase in synaptic strength. Notably, Nptx1 induction is mediated by calcium influx through the T-type Voltage-Gated Calcium Channel, as well as two transcription factors, SRF and ELK1. Taken together, 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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| Overall design |
mRNA profiles were generated from primary mouse cortical neurons at DIV12, comparing untreated neurons to neurons treated with Bicuculline or TTX for 30 m, 2 h, 4h, or 6 h, in duplicate
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| Contributor(s) |
Schaukowitch K, Reese AL, Kim S, Kilaru G, Joo J, Kavalali ET, Kim T |
| Citation(s) |
28178527 |
| |
| Submission date |
Dec 07, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Gokhul Krishna Kilaru |
| E-mail(s) |
gokhul.kilaru@utsouthwestern.edu
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| Phone |
214-648-4158
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| Organization name |
University of Texas Southwestern Medical Center
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| Department |
Department of Neuroscience
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| Lab |
Joseph S. Takahashi
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| Street address |
6000 Harry Hines Boulevard
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| City |
Dallas |
| State/province |
TEXAS |
| ZIP/Postal code |
75390 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA356606 |
| SRA |
SRP094701 |
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