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. 2019 Nov 29;9:17935. doi: 10.1038/s41598-019-54182-2

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© The Author(s) 2019

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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Neddylation is required for synaptic plasticity induction. (a) LTP was induced in acute hippocampal brain slices by high frequency stimulation (HFS). Application of 1 µM MLN-4924 5 min before starting induction (red bar) significantly decreased LTP compared to controls, while MLN-4924 added after the induction (yellow bar) did not affect LTP magnitude. (closed circles: control, red squares: MLN-4924 added before induction, yellow triangles: MLN-4924 after induction, open circles: MLN-4924 no LTP induction). (b) LTD could be induced under control conditions by low frequency stimulation (closed circles) and was strongly reduced when induced in the presence of MLN-4924 (red squares). Open circles show control fEPSP recordings from slices treated with MLN-4924 without inducing plasticity demonstrating that a short application of MLN-4924 does not directly affect synaptic transmission. Red bar indicates 1 µM MLN-4924 application. Insets on top show sample traces; solid line before induction, dashed line after induction. (closed circles: control, open squares: MLN-4924 before induction, open circles: MLN-4942 no LTD induction). (c) MLN-4924 does not directly inhibit NMDA receptor mediated currents. Please note, stimulus artefacts have been omitted for clarity.