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The Journal of Neuroscience, August 16, 2006, 26(33):8517-8522; doi:10.1523/JNEUROSCI.5279-05.2006

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Brief Communications
Estradiol-Induced Increase in the Magnitude of Long-Term Potentiation Is Prevented by Blocking NR2B-Containing Receptors

Caroline C. Smith and Lori L. McMahon

Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, Alabama 35294

Correspondence should be addressed to Dr. Lori L. McMahon, The University of Alabama at Birmingham, 1918 University Boulevard, McCallum Building 964, Birmingham, AL 35294-0005. Email: mcmahon{at}physiology.uab.edu

Estradiol, through activation of genomic estrogen receptors, induces changes in synaptic morphology and function in hippocampus, a brain region important for memory acquisition. Specifically, this hormone increases CA1 pyramidal cell dendritic spine density, NMDA receptor (NMDAR)-mediated transmission, and the magnitude of long-term potentiation (LTP) at CA3–CA1 synapses. We recently reported that the estradiol-induced increase in LTP magnitude occurs only when there is a simultaneous increase in the fractional contribution of NMDAR-mediated transmission relative to AMPA receptor transmission, suggesting a direct role for the increase in NMDAR transmission to the heightened LTP magnitude. Estradiol has been shown to increase expression of the NMDAR subunit NR2B, but whether this translates into an increase in function of NR2B-containing receptors remains to be determined. Here we show that not only is the estradiol-induced increase in NMDAR transmission mediated by NR2B-containing receptors, but blocking these receptors using RO25-6981 [R-(R,S)--(4-hydroxyphenyl)--methyl-4-(phenylmethyl)-1-piperidine propranol] (0.5 µM), an NR2B selective antagonist, prevents the estradiol-induced increase in LTP magnitude. Thus, our data show a causal link between the estradiol-induced increase in transmission mediated by NR2B-containing NMDARs and the increase in LTP magnitude.

Key words: estradiol; NMDA receptor; synaptic plasticity; hippocampus; LTP; NR2B

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Received Dec. 9, 2005; revised June 27, 2006; accepted June 29, 2006.

Correspondence should be addressed to Dr. Lori L. McMahon, The University of Alabama at Birmingham, 1918 University Boulevard, McCallum Building 964, Birmingham, AL 35294-0005. Email: mcmahon{at}physiology.uab.edu

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