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PLoS One. 2013 Dec 31;8(12):e83941. doi: 10.1371/journal.pone.0083941. eCollection 2013.

SynGAP regulates protein synthesis and homeostatic synaptic plasticity in developing cortical networks.

Author information

1
Neuroscience Program, School of Science and Engineering, Tulane University, New Orleans, Louisiana, United States of America.
2
Department of Cell and Molecular Biology, School of Science and Engineering, Tulane University, New Orleans, Louisiana, United States of America.
3
Neuroscience Program, School of Science and Engineering, Tulane University, New Orleans, Louisiana, United States of America ; Department of Cell and Molecular Biology, School of Science and Engineering, Tulane University, New Orleans, Louisiana, United States of America.

Abstract

Disrupting the balance between excitatory and inhibitory neurotransmission in the developing brain has been causally linked with intellectual disability (ID) and autism spectrum disorders (ASD). Excitatory synapse strength is regulated in the central nervous system by controlling the number of postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). De novo genetic mutations of the synaptic GTPase-activating protein (SynGAP) are associated with ID and ASD. SynGAP is enriched at excitatory synapses and genetic suppression of SynGAP increases excitatory synaptic strength. However, exactly how SynGAP acts to maintain synaptic AMPAR content is unclear. We show here that SynGAP limits excitatory synaptic strength, in part, by suppressing protein synthesis in cortical neurons. The data presented here from in vitro, rat and mouse cortical networks, demonstrate that regulation of translation by SynGAP involves ERK, mTOR, and the small GTP-binding protein Rheb. Furthermore, these data show that GluN2B-containing NMDARs and the cognitive kinase CaMKII act upstream of SynGAP and that this signaling cascade is required for proper translation-dependent homeostatic synaptic plasticity of excitatory synapses in developing cortical networks.

PMID:
24391850
PMCID:
PMC3877118
DOI:
10.1371/journal.pone.0083941
[Indexed for MEDLINE]
Free PMC Article

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