title: Rapid enhancement of two-step wiring plasticity by estrogen and NMDA receptor activity.
abstract: Cortical information storage requires combined changes in connectivity and synaptic strength between neurons, but the signaling mechanisms underlying this two-step wiring plasticity are unknown. Because acute 17beta-estradiol (E2) modulates cortical memory, we examined its effects on spine morphogenesis, AMPA receptor trafficking, and GTPase signaling in cortical neurons. Acute E2 application resulted in a rapid, transient increase in spine density, accompanied by temporary formation of silent synapses through reduced surface GluR1. These rapid effects of E2 were dependent on a Rap/AF-6/ERK1/2 pathway. Intriguingly, NMDA receptor (NMDAR) activation after E2 treatment potentiated silent synapses and elevated spine density for as long as 24 h. Hence, we show that E2 transiently increases neuronal connectivity by inducing dynamic nascent spines that "sample" the surrounding neuropil and that subsequent NMDAR activity is sufficient to stabilize or "hold" E2-mediated effects. This work describes a form of two-step wiring plasticity relevant for cortical memory and identifies targets that may facilitate recovery from brain injuries.
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. srivastava@northwestern.edu
authors.forename: Deepak P
authors.initials: DP
authors.lastname: Srivastava
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Woolfrey
authors.forename: Kevin
authors.initials: K
authors.lastname: Woolfrey
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Jones
authors.forename: Cassandra Y
authors.initials: CY
authors.lastname: Shum
authors.forename: L Leanne
authors.initials: LL
authors.lastname: Lash
authors.forename: Geoffrey T
authors.initials: GT
authors.lastname: Swanson
authors.forename: Peter
authors.initials: P
authors.lastname: Penzes
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000187:drug effects; D004798:Enzymes / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
chemical_list: D004798:Enzymes; D004958:Estradiol; D004967:Estrogens; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C473649:NR1A NMDA receptor, rat
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