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Fig. 3 | Translational Neurodegeneration

Fig. 3

From: Targeting galectin-3 to counteract spike-phase uncoupling of fast-spiking interneurons to gamma oscillations in Alzheimer’s disease

Fig. 3

Gal3-induced impairment of excitatory and inhibitory synaptic transmission during gamma oscillations. a Summary bar graphs of EPSC charge transfer in PCs in control conditions (gray) and 40 min after application of 2 µM gal3 (red) (control: 333.2 ± 44.4 pC, gal3: 253.9 ± 41.3 pC, n = 11, N = 6; P = 0.0423, one-tailed paired t-test). b Cumulative probability of PC EPSC amplitude in control conditions (gray) and 40 min after application of 2 µM gal3 (red). Inset: Quantification of mean amplitude (control: 25.7 ± 3.1 pA, gal3: 21.5 ± 3.68 pA, n = 11, N = 6; P = 0.2158, two-tailed paired t-test). c Cumulative probability of PC EPSC frequency in control conditions (gray) and 40 min after application of 2 µM gal3 (red). Inset: Quantification of mean frequency (control: 29.6 ± 0.91 Hz, gal3: 27.4 ± 0.79 Hz, n = 11, N = 6; P = 0.0046, two-tailed paired t-test). d EPSC amplitude distribution in conditions mentioned in a. Inset: Representative traces of EPSC recordings for each condition. e Summary bar graphs of IPSC charge transfer in PCs in control conditions (gray) and 40 min after application of 2 µM gal3 (red) (control: 2170 ± 395.4 pC, gal3: 1052 ± 171.3 pC, n = 9, N = 4; P = 0.0049, one-tailed paired t-test). f Cumulative probability of PC IPSC amplitude in control conditions (gray) and 40 min after application of 2 µM gal3 (red). Inset: Quantification of mean amplitude (control: 128.8 ± 26.3 pA, gal3: 59.5 ± 9.72 pA, n = 9, N = 4; P = 0.0143, two-tailed paired t-test). g Cumulative probability of PC IPSC frequency in control conditions (gray) and 40 min after 2 µM gal3 application (red). Inset: Quantification of mean frequency (control: 27.0 ± 1.17 Hz, gal3: 28.1 ± 0.74 Hz, n = 9, N = 4; P = 0.2004, two-tailed paired t-test). h IPSC amplitude distribution in conditions mentioned in e. Inset: Representative traces of IPSC recordings for each condition. i Coefficient of rhythmicity calculated from PC EPSCs in the conditions described in a (control: 0.82 ± 0.02, gal3: 0.75 ± 0.02, n = 11, N = 6; P = 0.0040, two-tailed paired t-test). j Analysis of the cross-correlation (XC) (LFP, EPSCs) peak size revealed that gal3 did not alter the LFP-EPSC similarity (control: 0.66 ± 0.04, gal3: 0.65 ± 0.06, n = 11, N = 6; P = 0.8994, two-tailed Wilcoxon test). k Top: Representative XC calculation performed between gamma LFP and EPSC signals in the conditions described in a. Bottom: Analysis of the peak lag of the XC (LFP, EPSCs) revealed that gal3 induced a phase shift in the maximal coordination between LFP and EPSCs (control: − 3.71 ± 0.54 ms, gal3: 2.43 ± 2.53, n = 7, N = 6; P = 0.0156, two-tailed Wilcoxon test). l Coefficient of rhythmicity calculated from PC IPSCs in the conditions described in e, showing that gal3 drastically affected IPSC rhythmicity (control: 0.87 ± 0.03, gal3: 0.84 ± 0.03, n = 7, N = 4; P = 0.0078, one-tailed Wilcoxon test). m Quantification of the XC (LFP, IPSCs) peak size showing that gal3 impaired LFP-IPSC similarity (control: 0.91 ± 0.01, gal3: 0.79 ± 0.04, n = 7, N = 4; P = 0.0078, one-tailed Wilcoxon test). n Top: Representative XC calculation performed between gamma LFP and IPSC signals. Bottom: Analysis of the peak lag of the XC (LFP, IPSCs) revealed that gal3 induced a non-significant phase shift in the maximal coordination between LFP and IPSCs (control: 0.91 ± 0.91 ms, gal3: 0.4 ± 0.94, n = 7, N = 4; P = 0.2969, two-tailed Wilcoxon test). o Quantification of the excitatory charge transfer (control: 142.8 ± 31.8 pC, gal3: 100.7 ± 19.6 pC, n = 7, N = 4; P = 0.0146, one-tailed Wilcoxon test). p Cumulative probability of FSN EPSC amplitude in control conditions (gray) and 40 min after application of 2 µM gal3 (red). Inset: Quantification of mean amplitude (control: 12.1 ± 2.5 pA, gal3: 8.59 ± 1.63 pA, n = 7, N = 4; P = 0.0313, two-tailed Wilcoxon test). q Cumulative probability of FSN EPSC frequency in control conditions (gray) and 40 min after application of 2 µM gal3 (red). Inset: Quantification of mean frequency (control: 33.0 ± 0.89 Hz, gal3: 33.8 ± 1.35 Hz, n = 7, N = 4; P = 0.6875, two-tailed Wilcoxon test). r FSN EPSC amplitude distribution in the conditions mentioned in o. Inset: Representative traces of EPSC recordings for each condition. Data are presented as mean ± SE. Significance levels are shown as *P < 0.05, **P < 0.01. IEI: Inter-event interval; n.s: no significant statistical difference; n: number of slices and cells recorded concomitantly; N: number of animals

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