Seizures can be triggered by stimulating non-cortical structures in the quaking mutant mouse

Mutant Quaking mice (C57BL/6J) display convulsive tonic-clonic seizures that can be either spontaneous or triggered by manipulation of the animal or by auditory stimulation. Several abnormalities have been found (especially in the noradrenergic system) in the brainstem of this mutant strain. We first verified by electrophysiological recording that the cerebral cortex was not involved in the generation or in the development of these fits. Then we showed that tonic-clonic seizures similar to those obtained in the freely moving animal were triggered by low-threshold (LT, 5-50 microA) or high-threshold (HT, 55-150 microA) stimuli performed during head restraint. LT stimuli were mostly efficient in a number of ponto-bulbar and mesencephalic structures, including several reticular nuclei, the locus coeruleus, the nucleus subcoeruleus and the red nucleus, whereas HT stimuli were generally necessary to trigger fits by stimulating the nuclei pontis, the substantia nigra, the central gray area and the cerebellar nuclei. Seizures were also provoked at the diencephalic level with LT stimulation delivered in the medial thalamic area, the nucleus reticularis thalami and some subthalamic regions (zona incerta, H field of Forel). In contrast, no fits were obtained by stimulating the cerebellar cortex and the inferior colliculus, the ventral and lateral groups of thalamic nuclei or the telencephalic regions (hippocampus, amygdala, caudate nucleus, putamen and cerebral cortex), with the exception of the globus pallidus.