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. 2021 Mar 17;109(6):947–956.e5. doi: 10.1016/j.neuron.2021.01.008

Figure 4.

Figure 4

Reduction and potentiation of habenular AMPAR transmission mimics and rescues stress-driven cognitive deficits

(A) Experimental timeline. Representative injection site of AAV-hM3Dq (scale bar: 100 μm).

(B) Example traces of AMPA/NMDA (scale bars: 30 pA and 10 ms). Boxplots and scatterplots of AMPA/NMDA from control/GFP mice (black: n = 3 mice/13 cells, 2.353 ± 0.4565), stress/GFP mice (red: n = 3 mice/11 cells, 0.4818 ± 0.1509), and control/M3Dq mice (blue: n = 3 mice/12 cells, 0.5575 ± 0.1453). One-way ANOVA (F2,33 = 12.18) with Holm-Sidak correction (∗∗∗p < 0.001, comparisons against control/GFP).

(C) Experimental timeline. Boxplots and scatterplots of the error incidence in control/GFP mice (black: n = 12 mice, 6.833 ± 1.043 during habituation and 4.167 ± 0.6134 during test), stress/GFP mice (red: n = 12 mice, 5.75 ± 0.7295 during habituation and 8.75 ± 1.262 during test), and control/M3Dq mice (blue: n = 15 mice, 5.533 ± 0.5152 during habituation and 8 ± 0.8338 during test). Two-way repeated-measure ANOVA (F1,36 = 2.342) with Sidak correction (∗p < 0.05, habituation versus test).

(D) Representative injection site of AAV-Rab5 (scale bar: 100 μm). Experimental timeline.

(E) Example traces of AMPA/NMDA (scale bars: 25 pA and 10 ms). Boxplots and scatterplots of AMPA/NMDA (GFP, black: n = 3 mice/15 cells, 2.391 ± 0.4619; Rab5, red: n = 5 mice/20 cells, 0.938 ± 0.116). Mann-Whitney test (U = 74.5, ∗p < 0.05).

(F) Boxplots and scatterplots of the error incidence (GFP, black: n = 13 mice, 6.538 ± 0.9715 during habituation and 5.231 ± 0.9881 during test; Rab5, red: n = 14 mice, 10.79 ± 1.1 during habituation and 10.43 ± 1.848 during test). Two-way repeated-measure ANOVA (F1,25 = 9.965, ∗∗p < 0.01, GFP versus Rab5 interaction).

(G) Representative injection site of AAV-PA-Rac1 and fiber implantation (scale bar: 200 μm).

(H) Experimental timeline. Boxplots and scatterplots of the error incidence in PA-Rac1 mice subjected to control/light (black: n = 11 mice, 6.636 ± 1.591 during habituation and 4.545 ± 1.729 during test), stress/no-light (red: n = 14 mice, 4.429 ± 0.9061 during habituation and 10.36 ± 1.393 during test), and stress/light (blue: n = 15 mice, 5.933 ± 0.8421 during habituation and 5 ± 1.317 during test). Two-way repeated-measure ANOVA (F1,37 = 0.9971) with Sidak correction (∗∗p < 0.01, habituation versus test).

(I) Example traces of AMPA/NMDA (scale bars: 20 pA and 5 ms). Boxplots and scatterplots of AMPA/NMDA from a cohort of mice in (H) (black: control/light, n = 2 mice/10 cells, 2.454 ± 0.466; red: stress/no-light, n = 3 mice/11 cells, 0.8827 ± 0.1408; blue: stress/light, n = 3 mice/14 cells, 1.726 ± 0.2739). One-way ANOVA (F2,32 = 5.882, ∗∗p < 0.01). Overlay of the stressed PA-Rac1 mice onto the correlation analysis of Figure 1J (open circles: individual values; closed circles: single-mouse averages; n = 6 mice/25 cells).

Data are represented with boxplots (median and quartiles) or mean ± SEM. See also Figure S4.