Extended Data Figure 8. Scg2 is a molecular effector of bidirectional perisomatic inhibitory plasticity.

a. qRT-PCR validation of conditional Scg2^fl/fl line, where normalized (Left) Scg2 and (Right) Fos RNA levels in cultured hippocampal neurons derived from Scg2^fl/fl mice are shown. Cultures were transduced with lentiviral Cre or ΔCre and membrane depolarized with KCl for 0 h or 6 h. n = 3 biological replicates. Mean ± SEM. Two-sided t-test, **p=0.002.

b. Schematic of intersectional genetic strategy to introduce ChR2 into CCK-INs and sparsely introduce shRNAs specifically into CA1 PCs of Dlx5/6^Flp;CCK^Cre mice.

c. Normalized differences in CCK-IPSC amplitudes between pairs of Scg2 shRNA^— and shRNA⁺ PCs depicted in d-f. Strd, n = 30/4; NE, n = 24/3; KA, n = 19/4. Ordinary one-way ANOVA, multiple comparisons corrected; NE, **p=0.005; KA, **p=0.002.

d-f. Scatter plots of CCK-IPSC amplitudes of pairs as in c. Representative traces from pairs of neurons shown; blue marks depict light onset. Scale: 100 pA, 40 ms.

g. (Top) Schematic of recording configuration. Scatter plots of (Bottom left) PV-IPSC or (Bottom right) CCK-IPSC amplitudes recorded from pairs of neurons of which one was non-transduced (WT) and the other expressed a Scg2 shRNA with an shRNA-resistant full-length Scg2 rescue construct. Normalized differences in IPSC amplitudes between pairs of neurons shown to the right of each scatter plot. PV, n = 19/6; CCK, n = 19/4. One-sample t-test (two-sided) with hypothetical mean of 0, *p=0.011.

(c-g) Each open circle represents a pair of simultaneously recorded neurons; closed circles represent mean ± SEM; n = number of pairs/mice.