RGD Reference Report - A critical and cell-autonomous role for MeCP2 in synaptic scaling up. - Rat Genome Database

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A critical and cell-autonomous role for MeCP2 in synaptic scaling up.

Authors: Blackman, Melissa P  Djukic, Biljana  Nelson, Sacha B  Turrigiano, Gina G 
Citation: Blackman MP, etal., J Neurosci. 2012 Sep 26;32(39):13529-36.
RGD ID: 12790708
Pubmed: PMID:23015442   (View Abstract at PubMed)
PMCID: PMC3483036   (View Article at PubMed Central)
DOI: DOI:10.1523/JNEUROSCI.3077-12.2012   (Journal Full-text)

Rett syndrome (Rett) is the leading genetic cause of mental retardation in females. Most cases of Rett are caused by loss-of-function mutations in the gene coding for the transcriptional regulator methyl-CpG binding protein 2 (MeCP2), but despite much effort, it remains unclear how a loss of MeCP2 function generates the neurological deficits of Rett. Here we show that MeCP2 plays an essential and cell-autonomous role in homeostatic synaptic scaling up in response to reduced firing or reduced sensory drive in rat visual cortical pyramidal neurons. We found that acute RNAi knockdown of MeCP2 blocked synaptic scaling within targeted neocortical pyramidal neurons. Furthermore, MeCP2 knockdown decreased excitatory synapse number without affecting basal mEPSC amplitude or AMPAR accumulation at spared synapses, demonstrating that MeCP2 acts cell-autonomously to maintain both excitatory synapse number and synaptic scaling in individual neocortical neurons. Finally, we used a mouse model of Rett to show that MeCP2 loss prevents homeostatic synaptic scaling up in response to visual deprivation in vivo, demonstrating for the first time that MeCP2 loss disrupts homeostatic plasticity within the intact developing neocortex. Our results establish MeCP2 as a critical mediator of synaptic scaling and raise the possibility that some of the neurological defects of Rett arise from a disruption of homeostatic plasticity.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of synaptic plasticity  IMP 12790708 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mecp2  (methyl CpG binding protein 2)


Additional Information