Functional implications of seizure-induced neurogenesis

The neurobiological doctrine governing the concept of neurogenesis has undergone a revolution in the past few years. What was once considered dubious is now well accepted: new neurons are born in the adult brain. Science fiction is quickly becoming a reality as scientists discover ways to convert skin, bone, or blood cells into neurons. In the epilepsy arena, widespread interest has developed because of the evidence that neurogenesis increases after seizures, trauma, and other insults or injuries that alter seizure susceptibility. This review discusses some of the initial studies in this field, and their often surprising functional implications. The emphasis will be on the granule cells of hippocampus, because they are perhaps more relevant to epilepsy than other areas in which neurogenesis occurs throughout life, the olfactory bulb and subventricular zone. In particular, the following questions will be addressed: 1. Do granule cells that are born in the adult brain become functional, and what are the limits of their function? Do they behave homogeneously? Results from our own laboratory have focused on cells that become established outside the normal boundaries of the granule cell layer, forming a group of "ectopic" granule cells in the hilar region. 2. Is increased neurogenesis beneficial, or might it actually exacerbate seizures? Evidence is presented that supports the hypothesis that new granule cells may not necessarily act to ameliorate seizures, and might even contribute to them. Furthermore, cognitive deficits following seizures might in part be due to new circuits that develop between new cells and the host brain. 3. How do the new cells interact with the host brain? Several changes occur in the dentate gyrus after seizures, and increased neurogenesis is only one of many. What is the interdependence of this multitude of changes, if any? 4. Is neurogenesis increased after seizures in man? Research suggests that the data from human epileptics are actually inconsistent with the studies in animal models of epilepsy, because there is little evidence of increased neurogenesis in epileptic tissue resected from intractable epileptics. Yet neurogenesis has been shown to occur in humans throughout adult life. What might be the reasons for these seemingly disparate results?