Figure 1.

Excitatory transmission onto LHb neurons guides cognitive performance during the T-maze task

(A) Schematic of the behavioral paradigm.

(B) Boxplots and scatterplots of the time to reach the arm containers (habituation, black: n = 28 mice/140 trials, 20.02 ± 1.006; test session, red: n = 29 mice/144 trials, 8.688 ± 0.5951). Mann-Whitney test (U = 2,602, ^∗∗∗p < 0.001).

(C) Boxplots and scatterplots of the error incidence (habituation, black: n = 31 mice, 5.839 ± 0.6258; test session, red: n = 31 mice, 6.29 ± 0.5888).

(D) Representative injection site of AAV-GCaMP6f and fiber implantation (scale bar: 100 μm). 3V, third ventricle; M/LHb, medial/lateral habenula; Th, thalamus.

(E) Single-mouse heatmap of LHb fluorescence aligned to entry into the non-rewarded container (error dip; scale bar: 2 s).

(F) Time course of the average LHb fluorescence aligned to entry into the non-rewarded container (error dip). Boxplots and scatterplots of the area under the curve (AUC) (habituation, black: n = 5 mice/40 trials, 8.191 ± 3.429; test session, red: n = 5 mice/74 trials, 25.86 ± 2.758). Mann-Whitney test (U = 830, ^∗∗∗p < 0.001).

(G) Representative injection site of AAV-JAWS and fiber implantation (scale bar: 200 μm). DG, dentate gyrus.

(H) Schematic of the behavioral paradigm. Red light during the test session, aligned to entry into the non-rewarded container.

(I) Boxplots and scatterplots of the error incidence in GFP mice (black: n = 12 mice, 5.75 ± 0.7739 during habituation and 5.75 ± 1.021 during test) and JAWS mice (red: n = 13 mice, 5.154 ± 0.972 during habituation and 13 ± 2.044 during test). Two-way repeated-measure ANOVA (F_1,23 = 8.306) with Sidak correction (^∗∗∗p < 0.001, habituation versus test).

(J) Experimental timeline. Example traces of AMPA/NMDA after the test session (scale bars: 10 pA and 10 ms). Correlation plot between AMPA/NMDA and error incidence of the test session (open circles: individual values; closed circles: single-mouse averages; n = 11 mice/43 cells). Pearson correlation (R² = 0.833, F_1,9 = 44.89, ^∗∗∗p < 0.001).

(K) Experimental timeline. Boxplots and scatterplots of the error incidence during habituation (n = 16 mice, 5.313 ± 0.7113). Example traces of AMPA/NMDA after habituation (scale bars: 10 pA and 5 ms). Correlation plot between AMPA/NMDA and error incidence during habituation (open circles: individual values; closed circles: single-mouse averages; n = 8 mice/33 cells). Pearson correlation (R² = 0.0838, F_1,6 = 0.5486, p = 0.487).

Data are represented with heatmaps, boxplots (median and quartiles), or mean ± SEM. See also Figure S1.