title: Molecular and cellular plasticity in developing epileptic brain.
abstract: Defined transgenic models of epilepsy in the mouse represent unique opportunities to examine interactions between synchronous synaptic activity and cellular programs of brain development. We are beginning to acquire a list of the kinds of genes favoring sudden, intermittent aberrant discharges in central neurons, and we have found that, rather than arising from a few gene superfamilies regulating membrane excitability, they are involved in many diverse functions of the cell. Whereas some primary gene defects impinge directly on membrane electrogenesis and neurotransmitter signaling at synapses, others are too far removed from these processes to clearly visualize the steps by which they promote epileptogenesis. We have tantalizing evidence that several, and probably all, epilepsy genes entrain some degree of secondary molecular and cellular plasticity, and we can guess that these downstream rearrangements may account for the delayed onset of epileptic phenotypes in some syndromes. It is too early to tell whether these, or other induced changes, provide the basis for the reversibility of some epilepsies. The diversity of epilepsy genes and their intervening cellular phenotypes promise to provide a rich source of novel molecular targets for therapeutic discovery and will have a lot to teach us in the future about the developmental potential of neural circuits in the mammalian brain.
authors.affiliation: Department of Neurology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Noebels
authors.forename: M L
authors.initials: ML
authors.lastname: Sutherland
authors.forename: W K
authors.initials: WK
authors.lastname: Nahm
authors.forename: E
authors.initials: E
authors.lastname: DiPasquale
mesh_terms: D000818:Animals; D004827:Epilepsy / Q000235:genetics* / Q000473:pathology*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000235:genetics* / Q000502:physiology