Figure 5.

Ank3-1b KO mouse PV interneurons are less responsive due to reduced intrinsic excitability. (a-c) In cell attached recordings, Ank3-1b^KO/KO-PVtom PV cells fire less than controls in response to extracellular field stimulation. The stimulation artifact is proportional to stimulation amplitude and is labeled (*) for each trace. (a) The threshold stimulus required to evoke a single AP is markedly increased in Ank3-1b^KO/KO-PVtom PV cells (41.7±30.5 pA vs. control: 12.9±7.2 pA, n=16; P=0.001). (b) Representative traces illustrate reduced maximal firing response of mutant cells (note large stimulation artifact amplitudes). (c) Significantly reduced excitability in Ank3-1b^KO/KO-PVtom PV cells (n=16; P=0.03, 0.003, 0.003, 0.005, 0.003, 0.003, 0.002, 0.007, 0.004, and 0.003) compared to control (n=14). (d–i) Ank3-1b^KO/KO-PVtom PV cells fire less than controls in response to current injection (whole cell recordings). (d) Representative recordings of AP trains show reduced firing responses in a mutant cell compared to WT control cell (injection current, 230 pA). (e) Firing frequency is significantly decreased in Ank3-1b^KO/KO-PVtom mice (n=9; P=0.19, 0.07, 0.12, 0.19, 0.14, 0.05, 0.03, 0.02 for each current) compared to control (n=7). (f) Threshold current is significantly increased (n=11; P=0.016). (g) Representative AP phase plots, with depolarized ascending phase (**) of mutant indicated. (h) AP voltage threshold (n = 11 mutant; 8 WT, P=0.004) and I, half-width (n = 13; P=0.004) are significantly increased in Ank3-1b^KO/KO-PVtom mice compared to control (n = 9).