Figure 2. Hyperactive Sst neurons lead to sustained disinhibition of L5-PN in TDP mice.
(a) Hyperactive Sst interneurons in M1 cortex of 3-week old TDP mice. Left: representative AP firings of Sst interneurons in response to 200 pA current injection, from SstCre::tdTomato (Ctrl) and TDP::SstCre::tdTomato (TDP) mice. Right: dot plots of resting membrane potential (RMP) and AP firing frequency (Ctrl and TDP, n = 23, 20 neurons, 3 mice; Mann-Whitney U-test). (b) Hypoactive Pv interneurons in M1 of 3-weeks old TDP mice. Left: representative AP firings of Pv interneurons in response to 200 pA current injection, from PvCre::tdTomato (Ctrl) and TDP::PvCre::tdTomato (TDP) mice. Right: dot plots of RMP and AP firing frequency (Ctrl and TDP, n = 34 and 29 neurons, 3 mice; Mann-Whitney U-test). (c) Pv interneurons exhibited increased frequency of sIPSC in 3-week TDP mice. Left: representative sIPSC traces from PvCre (Ctrl) and TDP::PvCre (TDP) mice injected with Cre dependent eYFP virus. Right: dot plots of frequency and amplitude of sIPSC (Ctrl and TDP, n = 39, 41 neurons, 3 mice; Mann-Whitney U-test). (d) Sustained hyperactive Sst interneurons in M1 cortex of 8-week old TDP mice. Left: representative AP firings of Sst interneurons in response to 300 pA current injection, from SstCre (Ctrl) and TDP::SstCre (TDP) mice injected with Cre dependent eYFP virus. Right: dot plots of RMP and AP firing frequency (Ctrl and TDP, n = 24, 28 neurons, 3 mice; Mann-Whitney U-test). (e) Photo-stimulation of ChR2 (10 ms, 20 Hz) and eNpHR3.0 (40 ms, 20 Hz) on Sst interneurons of M1 cortex induced changes in sIPSCs of L5-PN. Left: representative sIPSC traces of L5-PN before and after photo-stimulation of Sst interneurons, from 8-week old SstCre mice injected with Cre dependent ChR2 or eNpHR3.0 virus. Right: Population (open circles) and average (filled circles) of normalized ratio (“light on” over “light off”) in sIPSC charges of ChR2 and eNpHR3.0 (n = 15, 20 neurons, 3 mice; Wilcoxon Signed Rank Test). Error bars are mean ± SEM. *, p < 0.05; **, p < 0.01; N.S., not significant.