jerks; (ii) hyperkinetic running, often with repeated, large clonics
of all limbs and frequently incontinence and loss of postural equi-
librium; and (iii) dystonic or hypertonic posture of the trunk, limbs
and tail, often asymmetrically. Motor automatisms such as chew-
ing and grooming also occurred and some mice exhibited
four-limb tonic–clonic seizures (Fig. 2; Supplementary material
movie). Seizures often ended after hypertonic postures. Mice
were immobile for 2–3 min and sometimes catatonic after seizures.
At postnatal day 14, LGI1
/
mice became inactive, except during
seizures, and usually remained isolated in their cage. Heterozygous
LGI1
+/
and wild-type littermates never showed spontaneous epi-
leptic manifestations.
Video-EEG recording demonstrates
epileptic activity in LGI1
/
mice
Spontaneous seizures in LGI1
/
mice were studied in simultan-
eous video and intracranial EEG recordings from postnatal days
10–15 pups. Ictal epileptic EEG abnormalities were evident in all
homozygous LGI1
/
mice (n = 6), and 52 spontaneous electrocli-
nical seizures were recorded (Fig. 3A). Epileptic activity was never
detected in age-matched heterozygous LGI1
+/
(n = 5) (Fig. 3B) or
wild-type (n = 5) (Fig. 3C) littermates. Cortical EEG records from
LGI1
/
pups (n = 6) revealed sequences of several ictal electro-
graphic patterns: (i) low amplitude fast activities (18–47 Hz);
(ii) bursts or discharges of polyspikes of increasing amplitude
and decreasing frequency (20–27 Hz) and (iii) high amplitude
slow potentials, close to 1 Hz, with superimposed low-voltage
polyspikes (Fig. 3A). Ictal EEG activities were often bilateral, but
asymmetrical seizure terminations suggestive of partial seizures
were sometimes detected (Fig. 3D).
In three LGI1
/
pups, EEG signals were recorded from both
cortex and hippocampus (Fig. 4). Periods of physiological theta
rhythm were evident in the hippocampal EEG between seizures
(Fig. 4E). During seizures, ictal electrographic activities were re-
corded concomitantly in the cortex and hippocampus. Our data
suggest that seizures may be initiated in the hippocampus. They
were often preceded by a sharp wave or a spike and wave, of
larger amplitude in the hippocampus than in the cortex. Further,
seizures appeared to be initiated with low voltage fast activities
that started 1–2 s earlier in the hippocampus than in the cortex
(Fig. 4A). After prolonged seizures, EEG activity was profoundly
depressed (Fig. 4D) until interictal activity reappeared after a few
minutes. Interictal activities consisted of spikes, polyspikes, spikes
and waves and were more abundant in the hippocampus
(Fig. 4C). Brief ictal EEG discharges with no obvious behavioural
counterpart were also observed after the first seizures between
BA
C D
E F
Figure 2 Spontaneous seizures in homozygous LGI1
/
mice. Frames from a video recording of a spontaneous seizure in a postnatal
day 16 LGI1
/
mouse. (A) Onset of the seizure with forelimb and hind limb flexion and loss of postural equilibrium, (B) asymmetrical
tonic extension (arrow) with rigidity of the tail, (C) chewing mechanism (arrow), (D) beginning of the hypertonic phase, (E) hypertonic
phase with characteristic rigid hind limb extension and (F) postictal immobility. The behavioural seizure lasted for 100 s.
LGI1 knockout mice Brain 2010: 133; 2749–2762 | 2753
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