Figure 7.

Only transient inhibition of PV neurons in the subiculum. A, Distribution of hM4Di/RFP expressed after AAV-hM4Di injection. B, hM4Di is found in neurons and dendrites at the injection site. C–E, At the injection site, the majority of PV neurons was also labeled for RFP (a tag for hM4Di). F, PV-cre mice injected with AAV-hM4Di (n = 7) were treated after 12 d with saline (not indicated) and after 15 d with CNO (10 mg/kg, i.p.). Neither treatment resulted in acute or spontaneous seizures (EEG recordings for 5 d after CNO). G, To investigate whether CNO treatment was efficient, we injected additional 12 mice with CNO or saline on day 15 after AAV-hM4Di and 45 min later with a threshold dose of PTZ (30 mg/kg, i.p.). EEGs were monitored for a further 24 h. All CNO- and PTZ-injected mice (n = 6) showed acute C-SWDs (4.2 ± 1.14 per 24 h) and two mice showed acute seizures (one and three seizures, respectively) during the initial 2 h, indicating that GABAergic transmission is reduced after CNO injection (right bars). Six AAV-hM4Di-injected mice (n = 6) treated concomitantly with saline (instead of CNO) and later with PTZ revealed neither C-SWDs nor seizures (left bars). CA1 and CA3, Hippocampal sectors CA1 and CA3; DG, dentate gyrus; EC, entorhinal cortex; Sub, subiculum. Scale bars: A, 500 μm; E (for B–E), 25 μm.