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. 2021 Feb 17;26(6):1748–1760. doi: 10.1038/s41380-020-01001-0

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© The Author(s) 2021

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. 2 — A Electrodes placements (left) and theta-burst pairing (TBP) protocol (right) for LTP at SC-CA1 synapses. B No TBP-induced LTP at SC-CA1 synapses in Cacna1c^+/− slices. C TBP-induced robust homosynaptic LTP at SC-CA1 in Cacna1c^+/+ slices. D Summary of normalized change in EPSC amplitude at 30–35 min shown in (B) and (C). Effect of genotype on LTP: LR₍₁₎ = 5.16, p = 0.023; genotype × pathway interaction: LR₍₁₎ = 7, p = 0.0081. Pairwise comparisons of Test vs Control pathway for Cacna1c^+/−: p = 0.99, n = 17 (12: 4 females and 8 males); Cacna1c^+/+: p = 0.0057, n = 16(9). E Electrodes placements (left) and low-frequency stimulation (LFS-pairing) protocol (right) for SC-CA1 LTP. LFS-pairing induces SC-CA1 LTP in Cacna1c^+/− (F) and Cacna1c^+/+ slices (G). H Summary of EPSC amplitude change at 30–35 min shown in (F) and (G): no effect of genotype (LR₍₁₎ = 0.103, p = 0.748) or genotype × pathway interaction (LR₍₁₎ = 0.227, p = 0.633) on LTP. Pairwise Test vs Control for Cacna1c^+/−: p = 0.0027, n = 10(7); Cacna1c^+/+: p = 0.0011, n = 8(6). I Electrode placements (left) and TBP protocol (right) for LTP at TA-CA1 synapses. TBP induces homosynaptic TA-CA1 LTP in slices from Cacna1c^+/− (J) and Cacna1c^+/+ animals (K). L Summary of changes in normalized EPSC amplitude at 30–35 min shown in (F) and (G): no effect of genotype (LR₍₁₎ = 0.0258, p = 0.8724) and no genotype × pathway interaction (LR₍₁₎ = 0.065, p = 0.798); contrast Test versus Control pathways, in Cacna1c^+/−: p = 0.0093, n = 8(7); Cacna1c^+/+: p = 0.014, n = 7(5). Plots show EPSC amplitude time-course in Test and Control pathways, normalized to 5 min average before LTP induction (arrowheads). Insets: 5 min average EPSC waveforms before (1, black) and 30–35 min after (2, red) LTP induction; scale bars: 50 pA, 50 ms. Sample sizes given as cells(animals—all males unless indicated). Data presented as means ± SEM. *p < 0.05, **p < 0.01 determined by two-way ordinal regression (cumulative link model) followed by analysis of deviance (ANODE) (colour figure online).