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Induction of an Isoelectric Brain State to Investigate the Impact of Endogenous Synaptic Activity on Neuronal Excitability In Vivo
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An Intrinsic Transcriptional Program Underlying Synaptic Scaling during Activity Suppression.
Katie Schaukowitch1, Austin L Reese1, Seung-Kyoon Kim1
1Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA.
Cell Reports
|February 9, 2017
Summary
Neurons maintain stable activity by upregulating synaptic strength when activity is suppressed. This process involves a specific gene program, including Neuronal pentraxin-1 (Nptx1), crucial for synaptic plasticity.
Area of Science:
- Neuroscience
- Molecular Biology
- Synaptic Plasticity
Background:
- Homeostatic scaling stabilizes neuronal activity by adjusting synaptic strength.
- Activity suppression upregulates surface α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, increasing synaptic strength.
- The underlying transcriptional program for synaptic upscaling remained largely unknown.
Purpose of the Study:
- To elucidate the molecular and transcriptional mechanisms of homeostatic synaptic upscaling.
- To identify specific genes and regulatory pathways involved in response to neuronal activity suppression.
Main Methods:
- RNA sequencing (RNA-seq) to identify upregulated genes during activity blockade.
- Gene knockdown experiments to assess the functional role of identified genes.
- Investigated the role of calcium influx and transcription factors (SRF, ELK1) in gene regulation.
Main Results:
- Identified 73 genes upregulated during activity suppression.
- Neuronal pentraxin-1 (Nptx1) was rapidly induced and essential for synaptic strength increase.
- Nptx1 induction depends on T-type calcium channel activity and transcription factors SRF and ELK1.
Conclusions:
- Uncovered a specific transcriptional program activated by neuronal activity suppression.
- Demonstrated the critical role of Neuronal pentraxin-1 (Nptx1) in mediating homeostatic synaptic upscaling.
- Revealed the signaling pathway involving calcium and transcription factors regulating synaptic plasticity during homeostatic adjustments.
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