Contemporary methods in neurocytology and their application to the study of epilepsy

The contemporary neuroanatomist has a number of available methods to analyze epileptic brain tissue. Many studies have utilized Nissl- and Golgi-stained preparations to determine that gliosis and neuronal loss occur at epileptic foci as well as a decrease in the dendritic spine density. These structural changes did not reveal any specific basic mechanism that may cause epileptic activity. In contrast, the relatively newer techniques in neurocytology provide functional data that relate to the physiology and chemistry of the brain tissue. The use of immunocytochemical, histochemical, and receptor ligand-binding autoradiographic methods have aided in the understanding of cellular neurochemistry in both normal and epileptic tissue. In addition, the use of intracellular horseradish peroxidase and recording and quantitative morphological methods at both light- and electron-microscopic levels has helped gain insights into the functional state of synapses and neurons. Together, these methods have been utilized to help unravel the mystery of epilepsy. Our laboratory has utilized immunocytochemical and quantitative light- and electron-microscopic methods to analyze four models of epilepsy; two resemble posttraumatic focal epilepsy, and the other two are genetic models of epilepsy. Our data indicate that a preferential loss of cortical GABAergic, inhibitory terminals occurs at posttraumatic epileptic foci. In contrast, the genetic models of epilepsy did not display a loss of GABAergic terminals. Instead, specific brain regions of epileptic animals had an increased number of GABAergic neurons and terminals. These data indicate that two different neuronal circuits may provide the anatomical substrate for epileptic activity: loss of inhibition and disinhibition.