INBRED EPILEPSY-PRONE SUBSTRAIN OF BALB C MICE SHOWS ABSENCE OF THE CORPUS-CALLOSUM, AN ABNORMAL PROJECTION TO THE BASAL FOREBRAIN, AND BILATERAL PROJECTIONS TO THE THALAMUS/

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-re sistant (ER), have been examined to determine whether these substrains differ in regard to corpus callosum morphology. Further, this study a ddressed the issue of whether misrouted cortical axons form an aberran t pathway instead of the corpus callosum. Initial studies that examine d fresh brain tissue of adult animals revealed normal corpora callosa in all ER mice hut deficient or absent corpora callosa in all EP mice. Subsequently, Dil crystals were placed in the motor cortices of aldeh yde-fixed brains of 2-week-old animals to investigate cortical project ions in both inbred substrains of mice. Fluorescent microscopy reveale d that all of the ER animals had normal corpora callosa, whereas all E P animals exhibited either reduced corpora callosa (partially callosal ) or an absence (acallosal) of this structure. Both acallosal and part ially callosal EP mice displayed an extensive, aberrant projection to the basal forebrain as well as bilateral projections to midline and in tralaminar thalamic nuclei. The fibers projecting to the basal forebra in arose from the cortex, coursed toward the midline before turning ve ntrally along the midline, and appeared to terminate in the medial sep tal nucleus and the nucleus of the diagonal band. ER animals lacked th is aberrant cortical projection to the basal forebrain. Electron micro scopic results obtained from EP mice indicated that labeled axons in t his aberrant pathway formed axosomatic, axodendritic, and axospinous s ynapses with the neurons in the medial septal/diagonal band complex. T he function of the aberrant projection to the basal forebrain remains unknown but it may provide an abnormal excitatory input to a region th at 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.