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. 2018 Apr 18;24(8):1206–1219. doi: 10.1038/s41380-018-0034-4

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 5 — NMDA-LTD and NMDA-dependent synaptic pruning is abolished in Pyr-KO mice. a Cartoon of a CA3-CA1 synapse depicting the sequential effect of bath-application of NMDA [1] on eCB release [2], activation of CB1Rs [3], and lowering glutamate release [4]. b Three minute 20 µM NMDA induces persistent LTD in Pyr-WT (71.3 ± 0.96%; n = 12 slices/4 mice; p < 0.001 relative to baseline); no effect in Pyr-KO (103.6 ± 1.03 %; n = 10 slices, 4 mice); p < 0.001, 2-Way RM Anova. c PPR for NMDA-LTD in Pyr-WT: 1.76 ± 0.14 (n = 12 slices/4 mice) vs. Pyr-KO: 1.01 ± 0.16 (n = 10 slices, 4 mice); p < 0.001, 2-Way RM Anova. d NMDA-LTD in Pyr-WT in the presence of 5 µM AM251: 120.3 ± 1.5 % (n = 11 slices/4 mice) vs. Pyr-KO: 122.3 ± 1.0 % (n = 8 slices/3 mice); p = 0.37, 2-Way RM Anova. e PPR during NMDA-LTD in AM251 is comparable between Pyr-WT (0.994 ± 0.013; n = 11 slices/4 mice) vs. Pyr-KO (0.99 ± 0.015; n = 8 slices/3 mice); p = 0.73, 2-Way RM Anova. Data averaged during period from 40 to 90 min post-induction. f Example traces of mEPSCs from Pyr-WT and Pyr-KO before and after induction of NMDA-LTD with a brief (3 min) pulse of 20 µM NMDA. g Bar-graph of average mEPSC frequency, with overlaid individual cell values (black and white symbols). Pyr-WT baseline: 1.44 ± 0.10 Hz (n = 17 cells/6 mice) vs. Pyr-WT NMDA-LTD: 1.04 ± 0.07 Hz (n = 15 cells/6 mice); p = 0.047. Pyr-WT baseline vs. Pyr-KO baseline: 2.11 ± 0.17 Hz (n = 11 cells/4 mice); p = 0.001. Pyr-KO baseline vs. Pyr-KO NMDA-LTD: 1.76 ± 0.11 Hz (n = 15 cells/4 mice); p = 0.153. One-Way Anova with post-hoc Tukey for multiple comparisons. h Bar-graph of average mEPSC amplitude, with overlaid individual cell values (black and white symbols). Pyr-WT baseline: 8.11 ± 0.41 (n = 17 cells/6 mice) vs. Pyr-WT NMDA-LTD: 7.36 ± 0.27 (n = 15 cells/6 mice); p = 0.652; Pyr-KO baseline: 8.29 ± 0.48 (n = 11 cells/4 mice) vs. Pyr-KO NMDA-LTD: 8.23 ± 0.66 (n = 15 cells/4 mice); p = 1.00. Pyr-WT baseline vs. Pyr-KO baseline: p = 0.99. One-Way Anova with post-hoc Tukey for multiple comparisons.