Extended Data Fig. 9: A series of rescue and overexpression analyses suggest a critical role for the processing of SCG2.

a, b, Scatter plots of PV-IPSC (a) and CCK-IPSC (b) amplitudes recorded from mKate2⁺ pairs that are either Cre^— (WT) or Cre⁺ (KO). Scg2-KO neurons also expressed a Cre-dependent full-length SCG2 construct (Rescue WT) to rescue the loss of Scg2. PV, n = 22/5; CCK, n = 27/3. c, d, As in a, b but using a Cre-dependent non-cleavable SCG2 mutant (Rescue 9AA) instead, which failed to rescue the loss of Scg2. PV, n = 23/4; CCK, n = 23/4. e, f, Scatter plots of PV-IPSC (e) and CCK-IPSC (f) amplitudes recorded from untransduced (WT) and neighbouring full-length SCG2-overexpressing CA1 PCs (OE WT), showing that gain-of-function of SCG2 is sufficient to induce bidirectional perisomatic inhibitory plasticity in the absence of neural activity. PV, n = 20/5; CCK, n = 25/3. g, Western blot confirmation of stable expression of SCG2 and the non-cleavable SCG2 mutant (9AA-Mutant) constructs containing an HA-tag in 293T cells. Expression levels were measured by immunoblot analysis with HA antibody. Loading controls (GAPDH) were run on a separate blot (see Supplementary Fig. 2b for full scans). n = 2 biological replicates. h, i, As in e, f but with overexpression of the non-cleavable SCG2 mutant (9AA Mutant) instead, which failed to induce changes in inhibition. PV, n = 19/4; CCK, n = 16/3. In a–f, h, i, each open circle represents a pair of simultaneously recorded neurons; closed circles represent mean ± s.e.m; n = number of pairs/number of mice.