Rapid enhancement of two-step wiring plasticity by estrogen and NMDA receptor activity

Deepak P. Srivastava, Kevin Woolfrey, Kelly A. Jones, Cassandra Y. Shum, L. Leanne Lash, Geoffrey T. Swanson, Peter Penzes

Research output: Contribution to journalArticle

116 Scopus citations


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 17β-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.

Original languageEnglish (US)
Pages (from-to)14650-14655
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number38
StatePublished - Sep 23 2008

ASJC Scopus subject areas

  • General

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