Extended Data Fig. 3: Genetic inhibition of mTORC2 (but not mTORC1) reverses the increased excitatory synaptic transmission in Pten fb-KO mice.

(a-c) Summary data (a-b) and sample traces (c) show increased frequency (a, Control n = 7, Pten fb-KO n = 6, t = 4.62, P < 0.0001), but not amplitude (b, Control n = 7, Pten fb-KO n = 6, t = 0.47, P = 0.641) of spontaneous excitatory postsynaptic currents (sEPSCs) in CA1 neurons from Pten fb-KO mice compared to control littermates. Unlike in Pten-Rptor fb-DKO mice (n = 9; a, c, Control vs. Pten-Rptor fb-DKO: t = 6.26, P < 0.0001), in Pten-Rictor fb-DKO mice (n = 5), sEPSC frequency is restored to control values (a, c, Control vs. Pten-Rictor fb-DKO: t = 0.86, P = 0.99). Data are mean ± SEM. Statistics are based on one-way ANOVA followed by uncorrected two-sided Fisher’s LSD method for pairwise comparisons. (d-f) Summary data (d-e) and sample traces (f) show similar frequency (d, Control n = 8, Pten fb-KO n = 14, t = 0.47, P = 0.636) and amplitude (e, Control n = 8, Pten fb-KO n = 14, t = 0.09, P = 0.925) of spontaneous inhibitory postsynaptic currents (sIPSCs) in CA1 neurons from control and Pten fb-KO mice. Statistics were based two-sided Student’s t-test Data are mean ± SEM. (g) Input-output curves in CA1 pyramidal neurons show that Pten fb-KO mice and Pten-Rptor fb-DKO mice fired more action potentials (APs) than control littermates at 350pA or higher current injection (n = 7 per group, control vs. Pten fb-KO, 350pA: t = 2.76, P = 0.020; 400 pA: t = 3.23, P = 0.0041; 450 pA: t = 4.13, P = 0.0002). By contrast, the increased excitability in Pten fb-KO mice is reduced in Pten-Rictor fb-DKO mice (n = 7 per group, Pten fb-KO vs. Pten-Rictor fb-DKO, 350 pA: t = 2.76, P = 0.020; 400 pA: t = 3.05, P = 0.010; 450 pA: t = 3.42, P = 0.002. Data are mean ± SEM. Statistics were based on two-way ANOVA followed by Bonferroni’s two-sided multiple comparison test. (h) Representative response elicited in CA1 pyramidal neurons (at -70 mV) upon injection of 400 pA for 500 ms.