title: REST-dependent epigenetic remodeling promotes the developmental switch in synaptic NMDA receptors.
abstract: NMDA receptors (NMDARs) are critical to synaptogenesis, neural circuitry and higher cognitive functions. A hallmark feature of NMDARs is an early postnatal developmental switch from those containing primarily GluN2B to primarily GluN2A subunits. Although the switch in phenotype has been an area of intense interest for two decades, the mechanisms that trigger it and the link between experience and the switch are unclear. Here we show a new role for the transcriptional repressor REST in the developmental switch of synaptic NMDARs. REST is activated at a critical window of time and acts via epigenetic remodeling to repress Grin2b expression and alter NMDAR properties at rat hippocampal synapses. Knockdown of REST in vivo prevented the decline in GluN2B and developmental switch in NMDARs. Maternal deprivation impaired REST activation and acquisition of the mature NMDAR phenotype. Thus, REST is essential for experience-dependent fine-tuning of genes involved in synaptic plasticity.
authors.affiliation: Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Alma
authors.initials: A
authors.lastname: Rodenas-Ruano
authors.forename: Andrés E
authors.initials: AE
authors.lastname: Chávez
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Cossio
authors.forename: Pablo E
authors.initials: PE
authors.lastname: Castillo
authors.forename: R Suzanne
authors.initials: RS
authors.lastname: Zukin
mesh_terms: D000818:Animals; D063185:Epigenetic Repression / Q000235:genetics*; D055785:Gene Knockdown Techniques; D006624:Hippocampus / Q000254:growth & development* / Q000378:metabolism; D008426:Maternal Deprivation; D010641:Phenotype; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000235:genetics / Q000378:metabolism*; D000099229:RE1-Silencing Transcription Factor
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D012097:Repressor Proteins; D000099229:RE1-Silencing Transcription Factor; C121001:NR2B NMDA receptor