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Research ArticleNew Research, Cognition and Behavior

Chemogenetic Suppression of Medial Prefrontal-Dorsal Hippocampal Interactions Prevents Estrogenic Enhancement of Memory Consolidation in Female Mice

Jennifer J. Tuscher, Lisa R. Taxier, Jayson C. Schalk, Jacqueline M. Haertel and Karyn M. Frick
eNeuro 1 April 2019, 6 (2) ENEURO.0451-18.2019; https://doi.org/10.1523/ENEURO.0451-18.2019
Jennifer J. Tuscher
Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI 53211
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Lisa R. Taxier
Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI 53211
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Jayson C. Schalk
Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI 53211
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Jacqueline M. Haertel
Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI 53211
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Karyn M. Frick
Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI 53211
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    Figure 1.

    Infusion of E2 into the mPFC immediately after training enhances memory consolidation. Mice infused with E2 directly into the mPFC spent significantly more time than chance (dashed line at 15 s) with the novel object (A, C) when tested 48 h after training, or with the moved object (B, D) 24 h after training. Mice infused with vehicle (Veh) into the mPFC did not spend more time than chance with the novel or moved objects. These data suggest that E2 can improve the consolidation of object memories by acting directly in the mPFC. Bars represent the mean ± standard error of the mean (SEM); *p < 0.05 relative to chance and the vehicle group (n = 10–13/group).

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    Figure 2.

    mPFC E2 infusion increases apical spine density in the mPFC 2 h later. Relative to vehicle (Veh), apical but not basal, spine density was significantly increased in the mPFC 2 h after mPFC infusion of 5-µg E2 per hemisphere (A). mPFC infusion did not alter apical or basal spine density in CA1 2 h after mPFC infusion of E2 (B). Bars represent the mean ± SEM; *p < 0.05 relative to the vehicle group (n = 6–8/group). C, Representative photomicrographs of Golgi-impregnated secondary apical dendrites from pyramidal cells in Layer II/III of the mPFC. Under oil 100×.

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    Figure 3.

    hM4Di and eGFP viral expression in the mPFC is present three weeks after injection. Coronal sections (40 µm) of CaMKIIα-hM4Di-mCitrine DREADD (A, C) or CaMKIIα-eGFP control virus (B, D) in the mPFC of female mice three weeks after injection confirms virus expression throughout the mPFC. Blue puncta: DAPI, a marker of cell nuclei; yellow: mCitrine-tagged DREADD virus; green: eGFP-tagged control virus. Merged images provide additional spatial context for DREADD or control virus expression within the region of interest.

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    Figure 4.

    Chemogenetic suppression of the mPFC immediately after training prevents the memory enhancement induced by DH E2 infusion. Sham, eGFP, or hM4Di control groups receiving CNO+Veh did not spend significantly more time than chance (15 s) with the novel object when tested 48 h after OR training (A, C) or with the displaced object (B, D) 24 h after training. In contrast, sham or eGFP mice receiving CNO+E2 immediately after training did spend significantly more time than chance with the moved and novel objects, displaying intact OP and OR memory. However, hM4Di mice treated with CNO+E2 immediately after training did not demonstrate intact memory, suggesting that DREADD-mediated suppression of the mPFC blocks the beneficial mnemonic effects of DH-infused E2. Bars represent the mean ± SEM; *p < 0.05 relative to chance, all Veh-infused groups, and the hM4Di-E2 group (n = 9–11/group); +p < 0.05 relative to chance and the Sham+Veh-infused and hM4Di-E2 groups (n = 9–11/group).

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March/April 2019
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Chemogenetic Suppression of Medial Prefrontal-Dorsal Hippocampal Interactions Prevents Estrogenic Enhancement of Memory Consolidation in Female Mice
Jennifer J. Tuscher, Lisa R. Taxier, Jayson C. Schalk, Jacqueline M. Haertel, Karyn M. Frick
eNeuro 1 April 2019, 6 (2) ENEURO.0451-18.2019; DOI: 10.1523/ENEURO.0451-18.2019

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Chemogenetic Suppression of Medial Prefrontal-Dorsal Hippocampal Interactions Prevents Estrogenic Enhancement of Memory Consolidation in Female Mice
Jennifer J. Tuscher, Lisa R. Taxier, Jayson C. Schalk, Jacqueline M. Haertel, Karyn M. Frick
eNeuro 1 April 2019, 6 (2) ENEURO.0451-18.2019; DOI: 10.1523/ENEURO.0451-18.2019
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Keywords

  • DREADD
  • estradiol
  • hippocampus
  • mouse
  • prefrontal cortex
  • spine density

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