Secondly, understanding the cellular basis of aberrant synchronized discharges of neurons during epileptic seizures also yields insights into the mechanisms of normal synchronization in the
brain. Finally, the necessity to perform invasive electrode (depth and subdural) recordings in patients with epilepsy results in unique opportunities to study human cognitive processes at extremely high time resolution by recording Inhibitors,research,lifescience,medical field or even single unit potentials during cognitive tasks. This technique can be combined with different functional imaging techniques, which ideally complement invasive recordings from the human brain by providing excellent spatial resolution. Research into the basic mechanisms of epilepsy The study of idiopathic genetic epilepsies : how do single gene mutations cause epilepsy? Genetic factors are the major determinants in at least
40% of all epilepsies; these are designated Inhibitors,research,lifescience,medical as “idiopathic epilepsies.” Only about 2% of these idiopathic epilepsies are inherited as monogenic disorders, in which one gene conveys the major heritable impact, while environment and lifestyle Inhibitors,research,lifescience,medical play a limited role. Genetic studies have allowed identification of the first disease genes that define monogenic idiopathic epilepsies.1,2 In these cases, genetic studies have identified causal gene variants, many of them neuronal ion channels, receptors, or associated proteins. Subsequently, the function of these variants was examined carefully in expression Inhibitors,research,lifescience,medical systems, and selleck kinase inhibitor specific functional changes were found. These analyses, while compelling in implicating specific genes in idiopathic epilepsies, are not the last word in understanding how a gene mutation leads to a behavioral and clinical phenotype. We are beginning to obtain such an understanding in some instances from transgenic mouse models that carry disease-associated gene Inhibitors,research,lifescience,medical variants.3 The advantage of such models is that they harbor human disease-associated
gene variants, and can be examined at various points during the development second of epilepsy with in vitro and molecular techniques. The limitation of such models is that the mechanisms of epileptogenesis may not be the same in mice and humans, and that disease-associated human gene variants are expressed on a background of mouse genes that may interact in unexpected ways with the human ortholog. Nevertheless, such studies are increasingly part of an integrated strategy to understand the mechanisms of monogenic epilepsies involving both human genetics and physiological, and molecular studies in transgenic mouse models. The study of focal epilepsy What are the mechanisms of seizures? By far most types of epilepsies, however, are not monogenic.