Previous studies have shown the functional importance of the inferior colliculus (IC) for the propagation and initiation of audiogenic seizures 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) of genetically epilepsy-prone rats (GEPR-9s) as compared to Sprague-Dawley rats that do not display audiogenic seizures. Two independent anatomical methods were used to determine the number of GABAergic neurons, immunocytochemistry and in situ hybridization. In both types of preparation, the labeled cells in the ICCN appeared to be of different sizes but the number of small cells with diameters less than 15 microns showed the greatest increase. Nissl-stained sections showed that the total number of neurons in the ICCN was increased in GEPR-9s and indicated that the increase in GABAergic neurons was not due to a change in the phenotype of collicular neurons from non-GABAergic to GABAergic. The number of small neurons in Nissl-stained sections of the ICCN was shown to correlate with seizure severity in the offspring of crosses made between Sprague-Dawley rats and GEPR-9s. Furthermore, the GEPR-3s that display moderate seizures showed a significant increase in the number of small neurons in the ICCN, and the magnitude of this increase was predicted 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 the propagation of seizure activity from the site of seizure initiation in the ICCN. It remains to be resolved how the increase in small GABAergic neurons in the ICCN is responsible for the known pharmacological defects observed at GABAergic synapses.

BALB/c mice lack a corpus callosum in about 11% of the population. Two inbred substrains of BALB/c mice, epilepsy-prone (EP) and epilepsy-resistant (ER), have been examined to determine whether these substrains differ in regard to corpus callosum morphology. Further, this study addressed the issue of whether misrouted cortical axons form an aberrant pathway instead of the corpus callosum. Initial studies that examined fresh brain tissue of adult animals revealed normal corpora callosa in all ER mice but deficient or absent corpora callosa in all EP mice. Subsequently, Dil crystals were placed in the motor cortices of aldehyde-fixed brains of 2-week-old animals to investigate cortical projections in both inbred substrains of mice. Fluorescent microscopy revealed that all of the ER animals had normal corpora callosa, whereas all EP animals exhibited either reduced corpora callosa (partially callosal) or an absence (acallosal) of this structure. Both acallosal and partially callosal EP mice displayed an extensive, aberrant projection to the basal forebrain as well as bilateral projections to midline and intralaminar thalamic nuclei. The fibers projecting to the basal forebrain arose from the cortex, coursed toward the midline before turning ventrally along the midline, and appeared to terminate in the medial septal nucleus and the nucleus of the diagonal band. ER animals lacked this aberrant cortical projection to the basal forebrain. Electron microscopic results obtained from EP mice indicated that labeled axons in this aberrant pathway formed axosomatic, axodendritic, and axospinous synapses with the neurons in the medial septal/diagonal band complex. The function of the aberrant projection to the basal forebrain remains unknown but it may provide an abnormal excitatory input to a region that provides cholinergic and GABAergic input to the cerebral cortex and hippocampus. The additional projections to midline and contralateral intralaminar thalamic nuclei in EP mice may function to intensify the synchronization of bilateral discharges.