THE ROLE OF THE INFERIOR COLLICULUS IN A GENETIC MODEL OF AUDIOGENIC-SEIZURES

Previous studies have shown the functional importance of the inferior colliculus (IC) for the propagation and initiation of audiogenic seizu res in several models of epilepsy in rats. A review of the cell types and cytoarchitecture of the IC, including its three major subdivisions , is presented. Significant increases in GABA levels and the number of GABAergic neurons are found in the central nucleus of the IC (ICCN) o f genetically epilepsy-prone rats (GEPR-9s) as compared to Sprague-Daw ley rats that do not display audiogenic seizures. Two independent anat omical methods were used to determine the number of GABAergic neurons, immunocytochemistry and in situ hybridization. In both types of prepa ration, the labeled cells in the ICCN appeared to be of different size s but the number of small cells with diameters less than 15 mu m showe d the greatest increase. Nissl-stained sections showed that the total number of neurons in the ICCN was increased in GEPR-9s and indicated t hat the increase in GABAergic neurons was not due to a change in the p henotype of collicular neurons from non-GABAergic to GABAergic. The nu mber of small neurons in Nissl-stained sections of the ICCN was shown to correlate with seizure severity in the offspring of crosses made be tween Sprague-Dawley rats and GEPR-9s. Furthermore, the GEPR-3s that d isplay moderate seizures showed a significant increase in the number o f small neurons in the ICCN, and the magnitude of this increase was pr edicted from this correlation. Finally, the use of knife cuts through the midbrain indicated that the ICCN sends an important projection to the external nucleus and that this projection plays a vital role in th e propagation of seizure activity from the site of seizure initiation in the ICCN. It remains to be resolved how the increase in small GABAe rgic neurons in the ICCN is responsible for the known pharmacological defects observed at GABAergic synapses.