Genetic models of absence epilepsy: New concepts and insights
[S.l.] : Elsevier
InStein, J. (ed.), Reference module in neuroscience and biobehavioral psychology
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Stein, J. (ed.), Reference module in neuroscience and biobehavioral psychology
SubjectBiological psychology; DI-BCB_DCC_Theme 3: Plasticity and Memory; Biologische psychologie
The discovery, development and use of genetic rodent models of absence epilepsy have led to a new theory about the origin of absence seizures, which has gained impact within the international epilepsy community. A focal zone has been identified in the perioral region of the somatosensory cortex in WAG/Rij and GAERS, the two most commonly used and best characterized genetic absence models. From here the seizure spreads quickly over the cortex and to the thalamus. Network analyses reveal unique dynamics in cortico-thalamic, thalamo-cortical and intrathalamic network. Activity in the cortex start to lead activity in the thalamus already 2 s before SWD onset, this leading role persists throughout the seizure when other cortical and thalamic regions consistently lag behind this focal site. After the first 500-1000 ms of SWD onset, the thalamus and cortex form a complex oscillatory network, with feedforward and feedback control of various cortico-thalamic, thalamo-cortical and intrathalamic relations and spreading directions. Pharmacologic, neurophysiologic, and molecular studies confirm the existence of a highly excitable focal cortical zone. This finding has led to the identification of various new disease-related mechanisms in cortex and thalamus involved in the pathogenesis of absence seizures. The availability of fertile, otherwise healthy, and genuinely epileptic animals has also led to studies of gene-environment interactions and of the interaction of different seizure types. It has also led to the discovery that absence epilepsy is comorbid with various psychopathologies. The issue of comorbidities is gaining interest since it has become clear that not only depression, but also schizophrenia and anxiety disorders, occur more often in epilepsy patients than in the nonepileptic population. In models with two different seizure types such as amygdala kindled or audiogenic sensitive WAG/Rij's or GAERS, the interaction of various seizure types has been studied. Understanding this interaction is important given that many patients have mixed symptoms which are often difficult to treat. Experimental treatment options were explored such as various forms of electrical stimulation, including subcortical deep brain stimulation and new antiabsence drugs and mechanisms were explored. Antiepileptogenesis might be feasible in the genetic models, although its mechanisms remain unclear. Finally, the usage of the genetic animal models has been instrumental to the changed concepts regarding whether generalized epilepsies do really exist.
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