ABSTRACT
Over the last 25 years, neurobiologists have begun to unravel the cellular mechanisms that underlie epileptiform activity. Such investigations have two main objectives: [1] to develop new methods for treating, [curing], or preventing epilepsy; and [2] to learn more about the normal functioning of the human brain, at the cellular/molecular and neurological/psychological levels by analyzing abnormal brain functioning. The electroencephalogram [EF.G] spike is a marker for the hyperexcitable cortex and arises in or near an area with a high epileptogenic potential. The depolarizing shift [DS] that underlies the interictal discharge [ID] appears to be generated by a combination of excitatory synaptic currents and intrinsic voltage-dependent membrane currents. The hyperpolarization that follows the DS [post-DS-1 IT] hunts ID duration, determines ID frequency, and prevents ID deterioration into seizures. The disappearance of the post-DS I IP in some models is related to the onset of seizures and the spread of epileptiform activity. During the transition to seizures, the usually self-limited ID spreads in time and anatomical space. Several processes may intervene in the pathophysiolpgical dysfunction. These include enhancing GABA-mediated inhibition, dampening NMDA-mediated excitability, interfering with specific Ca[2+] currents in central neurons, and perhaps stimulating [gating] pathways