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. Author manuscript; available in PMC: 2018 May 1.
Published in final edited form as: Neurosci Biobehav Rev. 2016 Mar 31;76(Pt B):363–379. doi: 10.1016/j.neubiorev.2016.03.024

Figure 2.

Figure 2

(A) Treatment (20–30 min) of hippocampal sections with 50 nM 17b-Estradiol (E2) increased dendritic spine density in the stratum radiatum (shown) and stratum oriens (not shown) of the CA1 subregion of the dorsal hippocampus and shown in the biocytin filled pyramidal neurons (scale bar, 100mm). In parallel, infusion of 50 nM 17-b estradiol (E2) in the dorsal hippocampus of ovariectomized female mice 15 min prior to learning (habituation) and testing rapidly enhanced performance in the Object Placement (OP), Object Recognition (OR), and Social Recognition (SR) task within 40 min of treatments. In this specific paradigm vehicle control mice (only control for OP task is shown here) do not show learning while E2 treated mice did, as indicated by a significant increase from habituation (black bars) to test (white bars) in the percent of time spent investigating a novel or displaced stimulus vs a familiar stimulus. Within the same timeframe, patch clamping recordings from CA1 pyramidal neurons of learning-naïve mice showed a significant inhibitory effect of the same 50nM dose of E2 on the frequency of miniature Excitatory Postsynaptic Current (mEPSC) and on the amplitude of AMPA-induced membrane depolarization. This effects is consistent with the notion that E2 rapidly induces the formation of silent/immature synapses. * P<0.05, *** P<0.001 in comparison to vehicle control; # P<0.05, ## P<0.01, ### P<0.001 in comparison to habituation phase. Modified from Phan et al., PNAS 112: 16018–16023.

(B) Dorsal hippocampal mTOR activation is necessary for E2 to enhance object recognition memory consolidation. Levels of phospho-p42 ERK, but not phsopho-p44 ERK, are increased in ovariectomized mice 5 min after bilateral dorsal hippocampal infusion of 5 μg/hemisphere E2 (*p < 0.05 relative to vehicle). This effect was blocked by the ERK inhibitor U0126 (0.5 μg/hemisphere), the PI3K inhibitor LY298002 (0.005 μg/hemisphere), or the mTOR inhibitor rapamycin (0.25 μg/hemisphere). Each inhibitor also prevented E2 from enhancing object recognition memory; only mice infused with E2 alone spent more time than chance (15 s) with the novel object (*p < 0.05). Error bars=mean ± standard error of the mean (SEM). Phosphorylated ERK normalized to total ERK. Insets are representative Western blots of phosphorylated and total ERK. Adapted with permission from Fortress et al., 2013.