No. | Injection: AAV-FLEX- | Sub/CA1 | CA3 | PrS | PaS | DG | EC | C-SWD | Number of seizures | Days recorded |
---|---|---|---|---|---|---|---|---|---|---|
Group 1: AAV-FLEX-TeLC injected, no seizures | ||||||||||
1 | TeLC | ++ | + | ++ | ++ | + | ++ | − | 0 | 28 |
2 | TeLC | ++ | + | − | 0 | 32 | ||||
3 | TeLC | +++ | ++ | − | 0 | 48 | ||||
4 | TeLC | +++ | + | ++ | +++ | ++ | ++ | + | 0 | 55 |
5 | TeLC | +++ | +++ | + | ++ | +++ | + | 0 | 56 | |
6 | TeLC | ++ | + | 0 | 48 | |||||
7 | TeLC | ++ | + | 0 | 55 | |||||
8 | TeLC | +++ | ++ | ++ | +++ | +++ | ++ | + | 0 | 56 |
9 | TeLC | ++ | + | ++ | + | + | 0 | 55 | ||
Group 2: AAV-FLEX-TeLC injected, with seizures | ||||||||||
10 | TeLC | +++ | + | + | + | 1 | 35 | |||
11 | TeLC | ++ | + | ++ | ++ | ++ | + | 3 | 56 | |
12 | TeLC | +++ | + | +++ | + | + | + | 19 | 47 | |
13 | TeLC | ++ | ++ | +++ | +++ | ++ | + | 5 | 30 | |
14 | TeLC | +++ | + | + | 2 | 47 | ||||
15 | TeLC | +++ | + | ++ | + | 5 | 47 | |||
16 | TeLC | +++ | + | + | 2 | 18 | ||||
17 | TeLC | +++ | + | + | + | + | 6 | 32 | ||
18 | TeLC | +++ | + | ++ | +++ | +++ | + | 12 | 56 | |
19 | TeLC | ++ | ++ | + | 9 | 30 | ||||
20 | TeLC | +++ | + | + | + | 9 | 40 | |||
21 | TeLC | ++ | + | + | 6 | 30 | ||||
22 | TeLC | +++ | + | ++ | + | 9 | 25 | |||
23 | TeLC | ++ | + | 2 | 38 | |||||
24 | TeLC | ++ | + | 5 | 28 | |||||
25 | TeLC | +++ | + | ++ | + | 7 | 34 | |||
Group 3: AAV-FLEX-GFP injected | ||||||||||
26 | GFP | ++ | + | +++ | − | 0 | 56 | |||
27 | GFP | ++ | + | + | +++ | +++ | +++ | − | 0 | 55 |
28 | GFP | +++ | ++ | +++ | + | + | − | 0 | 47 | |
29 | GFP | n.e. | − | 0 | 55 | |||||
30 | GFP | n.e. | − | 0 | 43 | |||||
31 | GFP | +++ | ++ | +++ | +++ | ++ | ++ | − | 0 | 57 |
32 | GFP | ++ | − | 0 | 54 | |||||
33 | GFP | ++ | + | − | 0 | 52 | ||||
34 | GFP | ++ | ++ | ++ | +++ | ++ | + | − | 0 | 52 |
Group 4: AAV-FLEX-TeLC injected and 10 d later with PTZ | ||||||||||
35 | TeLC + PTZ | ++ | + | + | 14 | 28 | ||||
36 | TeLC + PTZ | ++ | + | 6 | 53 | |||||
37 | TeLC + PTZ | ++ | + | + | + | 43 se | 34 | |||
38 | TeLC + PTZ | ++ | + | + | 9 | 53 | ||||
39 | TeLC + PTZ | ++ | + | 9 | 52 | |||||
40 | TeLC + PTZ | ++ | + | + | 7 | 52 |
Injections were performed unilaterally into the ventral subiculum, and mice were subjected to telemetric EEG and video monitoring. Group 1 (1–9), Mice that revealed no spontaneous seizures, but (except 1–3) C-SWDs. Six of these mice (4–9) that had experienced C-SWDs but were seizure free at day 42 (Fig. 3) were then injected with a threshold dose of PTZ resulting in acute and then recurrent spontaneous seizures (Fig. 6). Group 2 (10–25), 16 of 25 AAV-TeLC-injected mice (10–25) revealed spontaneous recurrent seizures and C-SWDs. Group 3 (26–34), none of nine AAV-GFP-injected mice exhibited recurrent seizures and were considered as controls. The fact that these mice also did not present C-SWDs argues against an unspecific effect of vector injection. Group 4 (35–40), these mice were injected with AAV-TeLC and after 10 d with PTZ. They were seizure free after AAV-TeLC injection but exhibited acute and then spontaneous recurrent C-SWDs and seizures after PTZ injection. Mouse 37 died from a status epilepticus on day 34. Expression of GFP (tag for AAV-TeLC) was most prominent in the subiculum/sector CA1, often extending to the presubiculum and parasubiculum, and, in some instances to the entorhinal cortex or to the dentate gyrus. se, Status epilepticus; PrS, presubiculum; PaS, parasubiculum; EC, entorhinal cortex; DG, dentate gyrus; n.e., not evaluated.