QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, October 14, 2009, 29(41):12982-12993; doi:10.1523/JNEUROSCI.3059-09.2009

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Kramár, E. A. Articles by Lynch, G. PubMed PubMed Citation Articles by Kramár, E. A. Articles by Lynch, G.

 Previous Article  |  Next Article 

Development/Plasticity/Repair
Cytoskeletal Changes Underlie Estrogen's Acute Effects on Synaptic Transmission and Plasticity

Enikö A. Kramár,¹ Lulu Y. Chen,² Nicholas J. Brandon,³ Christopher S. Rex,¹ Feng Liu,³ Christine M. Gall,² and Gary Lynch^1,2

¹Departments of Psychiatry and Human Behavior and ²Anatomy and Neurobiology, University of California, Irvine, California 92697, and ³Wyeth Research, Discovery Neuroscience, Monmouth Junction, New Jersey 08852

Correspondence should be addressed to Enikö A. Kramár, Gillespie Neuroscience Research Facility, 837 Health Science Road, University of California, Irvine, CA 92697. Email: ekramar{at}uci.edu

Estrogen, in addition to its genomic effects in brain, causes rapid and reversible changes to synaptic operations. We report here that these acute actions are due to selective activation of an actin-signaling cascade normally used in the production of long-term potentiation (LTP). Estrogen, or a selective agonist of the steroid's β-receptor, caused a modest increase in fast glutamatergic transmission and a pronounced facilitation of LTP in adult hippocampal slices; both effects were completely eliminated by latrunculin, a toxin that prevents actin filament assembly. Estrogen also increased spine concentrations of filamentous actin and strongly enhanced its polymerization in association with LTP. A search for the origins of these effects showed that estrogen activates the small GTPase RhoA and phosphorylates (inactivates) the actin severing protein cofilin, a downstream target of RhoA. Moreover, an antagonist of RhoA kinase (ROCK) blocked estrogen's synaptic effects. Estrogen thus emerges as a positive modulator of a RhoA>ROCK>LIM kinase>cofilin pathway that regulates the subsynaptic cytoskeleton. It does not, however, strongly affect a second LTP-related pathway, involving the GTPases Rac and Cdc42 and their effector p21-activated kinase, which may explain why its acute effects are reversible. Finally, ovariectomy depressed RhoA activity, spine cytoskeletal plasticity, and LTP, whereas brief infusions of estrogen rescued plasticity, suggesting that the deficits in plasticity arise from acute, as well as genomic, consequences of hormone loss.

---

Received June 27, 2009; revised July 27, 2009; accepted Aug. 1, 2009.

Correspondence should be addressed to Enikö A. Kramár, Gillespie Neuroscience Research Facility, 837 Health Science Road, University of California, Irvine, CA 92697. Email: ekramar{at}uci.edu

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help