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. 2021 Aug 25;12:5116. doi: 10.1038/s41467-021-25356-2

Fig. 4. Stimulated Shank2–/– Pv neurons fail to inhibit target PNs while displaying unaltered baseline synaptic transmission and excitability.

Fig. 4

a Normal frequency and amplitude of sEPSCs in pyramidal neurons (PNs) in the Shank2–/– mPFC (prelimbic, layer 2/3, 12–13 weeks) (n = 14 neurons, 4 mice [WT], 15/4 [KO], ns, not significant, two-tailed Student’s t-test [frequency], two-tailed Mann–Whitney test [amplitude]). b Normal sIPSCs in Shank2–/– mPFC PNs (n = 19/6 [WT], 18/4 [KO], ns, not significant, two-tailed Mann–Whitney test). c Normal excitability in Shank2–/– mPFC PNs, as indicated by input-output curve (n = 21/5 [WT], 13/5 [KO], ns, not significant, two-way RM-ANOVA). d Normal sEPSCs in Shank2–/– mPFC Pv neurons (n = 13/4 mice [WT], 15/4 [KO], ns, not significant, two-tailed Student’s t-test [frequency], two-tailed Mann–Whitney test [amplitude]). e Normal sIPSCs in Shank2–/– mPFC Pv neurons. Pv neurons were visualized by 3-week AAV-DIO-ChR2-EYFP infection (n = 23/6 [WT], 28/8 [KO], ns, not significant, two-tailed Student’s t-test). f Normal excitability in Shank2–/– mPFC Pv neurons (n = 24/6 [WT], 19/4 [KO], two-way RM-ANOVA). g–i WT Pv neuronal stimulation at 10 Hz (ChR2, 473 nm, 5 ms) inhibits PN firings in the mPFC (prelimbic, layer 2/3), whereas Shank2–/– Pv neuronal stimulation fails to inhibit PN firings, as shown by firing rates plotted across simulated EPSCs (siEPSCs), involving random current injections similar to in vivo situations21. mPFC Pv neurons infected with AAV-DIO-ChR2-EYFP were stimulated with siEPSC injections in the presence or absence of Pv neuronal light stimulation (n = 8/3 [WT-off], 9/3 [WT-on], 17/6 [KO-off] and 17/6 [KO-on], *p < 0.05, two-way ANOVA with Tukey’s test and Mann–Whitney test). j, k Pv neuronal stimulation suppresses PN discharges in both WT and Shank2–/– mPFCs during the short (~100 ms) time window immediately after 5-ms light stimulation, although the changes were smaller and normalized within ~20 ms after stimulation in Shank2–/– Pv neurons (n = 8/3 [WT-off], 9/3 [WT-on], 17/6 [KO-off], and 17/6 [KO-on], *p < 0.05, two-tailed Mann–Whitney test). See Source data for raw data values and Supplementary Table 1 for statistical details.