Fig.2

Expressing LGI1^W183R in excitatory neurons increases seizure susceptibility. A Gene targeting strategy for the generation of LGI1^flox/flox mice. B AAV9-DIO-LGI1^WT-GFP or AAV9-DIO-LGI1^W183R-GFP is expressed in cKO or Het excitatory neurons (CaMKII-Cre). Viruses are bilaterally injected into the ventricles (P0). cKO mice subjected to video observation and electrophysiological recording at P17–20 and Het mice are subjected to PTZ treatment and EEG recording at P35. C Representative images for triple fluorescence, GFP, CaMKII(CKII) and DAPI, in the hippocampus (hip) and temporal cortex (temp lb) of cKO mice (P17) (scale bars: 1 mm (whole brain); 50 μm (magnified). D Number ratios of GFP + vs CaMKII-Cre + cells in cKO and Het mice expressing LGI1^WT or LGI1^W183R (n = 5 per group). At P17–20, the ratio of GFP + vs CaMKII + is 43 ± 4 (CA1; LGI1^WT) and 42 ± 4 (CA1; LGI1^W183R), P = 0.86; 41 ± 4 (temp lb; LGI1^WT) and 42 ± 5 (temp lb; LGI1^W183R), P = 0.86. At P35, the ratio of GFP + vs CaMKII + is 44 ± 5 (CA1; LGI1^WT) and 44 ± 5 (CA1; LGI1^W183R), P = 0.98; 42 ± 3 (temp lb; LGI1^WT) and 38 ± 5 (temp lb; LGI1^W183R), P = 0.47. E Kaplan–Meier survival curves. F Quantification of reactions to PTZ injection. Latency to generalized seizure (GS): 383 ± 50 s (Het::LGI1^WT; n = 5) and 212 ± 33 s (Het::LGI1^W183R; n = 10), P = 0.023. G Representative EEGs and power spectral analysis in Het::LGI1^WT and Het::LGI1^W183R mice (P35) during PTZ-induced seizures. G Enlarged view of EEGs in G. H Spectral analysis of the EEGs. Grey dots indicate individual data points. *P < 0.05