Role of the Superior Colliculus and the Intercollicular Nucleus in the Brainstem Seizure Circuitry of the Genetically Epilepsy‐prone Rat

Abstract

Summary:Purpose: The neuronal network responsible for the convulsive behavior associated with sound-induced seizures in genetically epilepsy-prone rats (GEPRs) is believed to include the inferior colliculus and other brainstem structures such as the deep layers of the superior colliculus (DLSC), periaqueductal gray, and pontine reticular formation. However, previous studies also suggested that the DLSC and the nearby intercollicular nucleus (ICN) are part of a midbrain anticonvulsant zone capable of suppressing tonic convulsions when activated with bicuculline. Our aim in this study was to investigate the role of the superior colliculus (SC) and the ICN in generalized tonicclonic seizures (GTCSs).Methods: Bilateral lesions of the SC and the ICN as well as bicuculline infusions into the ICN were used to assess the role of this dorsal midbrain region in brainstem seizures induced by sound stimulation in GEPR-9s and GEPR-3s.Results: Lesions of the SC markedly attenuated audiogenic seizure (AGS) severity by abolishing all behavioral components except the wild running. Lesions of the ICN significantly reduced seizure severity in GEPR-9s, but were somewhat less effective than SC lesions. Bicuculline infusion into the deep layers of the SC and/or the ICN produced audiogenic-like seizures in GEPR-9s.Conclusions: These findings support the hypothesis that the SC and ICN are important components of the brainstem seizure network, but suggest they are not necessary for the wildrunning component of the seizure. The results further indicate that stimulation of the tectum facilitates GTCSs. Thus these findings suggest that the dorsal midbrain, when stimulated, is proconvulsant rather than anticonvulsant regarding brainstem seizures in GEPRs. Key Words: Brainstem seizure-Superior colliculus-Bicuculline-Seizure network.The genetically epilepsy-prone rat (GEPR), a welldescribed animal model of the epilepsies, displays generalized tonic-clonic seizures (GTCS) in response to sound stimulation (1). There are two independently derived strains of GEPRs. The GEPR-3 displays a soundinduced wild run followed by generalized clonus in all limbs, whereas the GEPR-9 typically exhibits a wild run followed by complete tonic extension of the fore-and hindlimbs (see 1 for more complete description of the convulsive behavior). Although a complete description of the essential circuitry for GTCSs in GEPRs is not known, it is clear that the neuronal network for these seizures resides within the brainstem (2). Although it is clear that the forebrain is not necessary for the soundinduced convulsive behavior in GEPRs, several laboratories have shown that repeated audiogenic seizures can result in the activation of a forebrain seizure circuitry along with the concomitant expression of limbic motor convulsions (i.e., facial and forelimb clonus) (3-5). Moreover, recent findings have shown that even after three seizure tests, the current generation of GEPR-9s at the University of Illinois commonly, but not always, displays EEG evidence of cortical discharg...

CBF changes in drug naive juvenile myoclonic epilepsy patients

“…To test the prior hypothesis of thalamus and brainstem dysfunction in idiopathic generalized epilepsy [4,5,11,28,30,34], small volume correction (SVC) was adjusted in these areas.…”

“…Low concentrations of thalamic N-acetylaspartate (NAA) were reported in JME [4,30], and thalamocortical network was emphasized for the genesis of generalized epilepsy [5]. The critical role of brainstem in generalized seizures has also been reported in the animal studies [11,28,34]. Antiepileptic drug (AED) affects regional cerebral blood flow (rCBF), cerebral glucose metabolism, and neurotransmitter systems [6,15,39,43,44].…”

The genetic audiogenic seizure hamster from Salamanca: The GASH:Sal

“…The high Fos immunoreactivity in the ECIC is consistent with a key role in triggering the AGS, since this IC subnucleus has outputs, in addition to primary acoustic structures, to subcortical integrative sensorimotor nuclei [77][78][79][80]. Our data also showed significant overexpression of the c-fos gene in the PAG in the GASH:Sal hamsters, which is consistent with studies in other strains that have AGS (GEPR-9 rats [81], C57BL/6J mice, and DBA/2J mice [66]).…”

Cerebral blood flow abnormality in patients with idiopathic generalized epilepsy

“…The unpaired t-test was used for the group comparisons between the controls and IGE patients. To test the prior hypothesis of thalamus and brainstem dysfunction in IGE [3,15,29,31], a small volume correction (SVC) was made in these areas.…”

“…The superior colliculus is a paired structure and comprises the rostral aspect of the midbrain and is situated posterior to the periaqueductal gray matter. The superior colliculus and the nearby intercollicular nucleus are parts of a midbrain anticonvulsant zone capable of suppressing generalized tonic-clonic seizures [29] and are also important components of the brainstem seizure network [31].An excitatory amino acid is thought to play a major role in neurotransmission in the superior colliculus [21] and considerable evidence for glutamatergic modulation of audiogenic seizures has also been observed. [15] The brainstem auditory evoked potentials were found to be abnormal in patients with generalized epilepsy, whereas the evoked potentials recorded from patients with focal epilepsy were normal [23].…”