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. 2019 Oct 23;10:4814. doi: 10.1038/s41467-019-12736-y

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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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Fig. 4 — Synapse-specific changes to short-term plasticity in P10–11 Fmr1-KO mouse. a Top: Example voltage-clamped synaptic currents during repetitive TC stimulation at 50 Hz. Note strong amplitude attenuation of TC-evoked and FFI currents in Fmr1^−/Y. Bottom: Instantaneous G/A ratios for the above traces calculated by dividing FF-IPSC amplitudes by EPSCs for each sampled point in time. Note: (1) the graded attenuation of G/A ratio in the Fmr1^+/Y and slow onset of G/A balance during stimulus train despite large amplitude FF-IPSC, (2) Temporally disorganised ratio in the Fmr1^−/Y. Arrows show stimulation times. Scale: 50 ms/100 pA, G/A = 1. b Short-term depression of EPSCs and FF-IPSCs during 5 × 50 Hz stimulation: Evoked current amplitudes normalized to steady-state amplitude. Error bars: mean ± SEM normalized peak amplitude after for each stimulus for Fmr1^+/Y (blue, N = 19 (EPSCs) and N = 11 (FF-IPSCs) neurons) and Fmr1^−/Y (red, N = 15 (EPSCs) and N = 12 (FF-IPSCs) neurons). Asterisks: significantly different stimulus responses between genotypes (t-test, p < 0.05). Shaded regions are best ± 95% CI fits to bi-exponential decay functions. For both EPSCs and FF-IPSCs, the rate of depression for Fmr1^−/Y responses was faster and a single (i.e. common) fit could not adequately explain the behaviour of both genotypes (Extra sum-of-squares F-test, EPSCs: p = 0.0007, F(2,163) = 7.65, IPSCs: p = 0.0002, F(2,111) = 9.45, N’s as above). c Data from (b) represented as stimulus-by-stimulus G/A ratios from FF-IPSCs by EPSCs. Inset shows data normalised to starting G/A ratios. Asterisks indicate stimuli with significant reductions in G/A ratio for Fmr1^−/Y data (t-test, N’s as in (b)). d Example short-term depression (50 Hz stimulus frequency) of unitary connections between FS-SC and SC-FS neurons (left, right) from paired recordings. Single trials shown. Scale: 50 mV, 10 pA/50 ms. e Short-term plasticity analysis in (b) but for unitary connections tested between connected pairs of FS and SC neurons (Asterisks: p < 0.05, t-test, fits: (p < 0.05, Extra sum-of-squares F-test N: FS to SC Fmr1^+/Y = 9, Fmr1^−/Y = 8, SC to FS: Fmr1^+/Y = 9, Fmr1^−/Y = 6). N’s indicate neurons). f As for (d) but for example connected SC–SC paired recording. Scale: 50 mV, 5 pA/25 ms. g Short-term depression of SC–SC connections was indistinguishable between genotypes (p < 0.05, t-test, N = 17 Fmr1^+/Y, 11 Fmr1^−/Y)