Had alterations occurred, and if seizures begot seizures, then this would not be the case. However, it may be worth stressing that antiepileptic regimens are usually pursued after successful surgery; this is not readily compatible with a completely focal origin and restriction of the events. In addition, the removal in successful operations of large samples of the presumed focus may reflect the need to remove generators other than the identified

focus, possibly because of generalization of seizures and alterations of sites distal to the focus. In other terms, we do not know at present whether the morphological substrate Inhibitors,research,lifescience,medical of the focus corresponds exactly to the electrical pacemaker cell assembly. I suggest that this is not the case, and that an ensemble of neurons outside the focus – in the vicinity of, or in distal regions connected to the focus – contribute to the damage and the Inhibitors,research,lifescience,medical seizures. However,

additional experiments are clearly needed to clarify how many seizures lead to INK 128 order synapse reorganizations, and how this contributes to the formation of distal independent pacemaker cell assemblies (sec also below). We need to compare the extent of the damage after a few seizures to that observed after a long Inhibitors,research,lifescience,medical period of ongoing seizures. Inhibitors,research,lifescience,medical My predictions are that these will differ significantly. The second implication is that epileptic networks may well operate differently from naive ones, independently of the epileptogenicity. Thus, if aberrant synapses operate

with different receptors, the generation of behaviorally relevant oscillations by the network will be Inhibitors,research,lifescience,medical affected. The kinetics of epileptic kainite-mediated synaptic currents is much longer than the naive AM’PA currents, and thus the generation of high-frequency oscillations and the integrative properties are expected to be affected. Since epileptic networks use similar ensembles to those that generate important integrative functions, they are expected to impact these functions. In keeping with this, place cells operate differently in naive hippocampi and in epileptic ones.72 The third implication is that reactive plasticity should be taken more into account in our understanding of medroxyprogesterone epilepsies, and possibly also neurodegenerative disorders. If synapses reorganize, new ones are formed, and a fortiori if these operate by different receptors and intracellular signals, then it may be worth using genuine epileptic networks to understand the underlying mechanisms and develop new antiepileptic drugs and regimens. Using a naive network that seizes acutely under the influence of a convulsive agent is to a large extent irrelevant.