An Intrinsic Transcriptional Program Underlying Synaptic Scaling during Activity Suppression.
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.
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA.
Katie
K
Schaukowitch
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA.
Austin L
AL
Reese
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA.
Seung-Kyoon
SK
Kim
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA.
Gokhul
G
Kilaru
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA.
Jae-Yeol
JY
Joo
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA.
Ege T
ET
Kavalali
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA. Electronic address: taekyung.kim@utsouthwestern.edu.
Tae-Kyung
TK
Kim
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000378:metabolism; D002478:Cells, Cultured; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D018091:Receptors, AMPA / Q000378:metabolism; D013569:Synapses / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology
D020747:Calcium Channels, T-Type; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D014157:Transcription Factors; D002118:Calcium
Nptx1; T-VGCC; enhancer; homeostatic scaling; transcription