Estradiol potentiation of NR2B-dependent EPSCs is not due to changes in NR2B protein expression or phosphorylation.
The hormone, 17β-estradiol (E2), influences the structure and function of synapses in the CA1 region of the hippocampus. E2 increases the density of dendritic spines and excitatory synapses on CA1 pyramidal cells, increases CA1 cells' sensitivity to excitatory synaptic input mediated by the NMDA receptor (NMDAR), enhances NMDAR-dependent long-term potentiation, and improves hippocampus-dependent working memory. Smith and McMahon (2006 J Neurosci 26:8517-8522) reported that the larger NMDAR-mediated excitatory postsynaptic currents (EPSCs) recorded after E2 treatment are due primarily to an increased contribution of NR2B-containing NMDARs. We used a combination of electrophysiology, Western blot, and immunofluorescence to investigate two potential mechanisms by which E2 could enhance NR2B-dependent EPSCs: An increase in NMDAR subunit protein levels and/or a change(s) in NR2B phosphorylation. Our studies confirmed the E2-induced increase in NR2B-dependent EPSC amplitude, but we found no evidence that E2 affects protein levels for the NR1, NR2A, or NR2B subunit of the NMDAR, nor that E2 affects phosphorylation of NR2B. Our findings suggest that the effects of E2 on NMDAR-dependent synaptic physiology in the hippocampus likely result from recruitment of NR2B-containing NMDARs to synapses rather than from increased expression of NMDARs or changes in their phosphorylation state.
Snyder
Melissa A
MA
Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois, USA.
Cooke
Bradley M
BM
Woolley
Catherine S
CS
D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism*; D049229:Dendritic Spines / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D021122:Protein Subunits / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism
C121001:NR2B NMDA receptor; D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate; D004958:Estradiol