NEOCORTEX IN THE HIPPOCAMPUS - AN ANATOMICAL AND FUNCTIONAL-STUDY OF CA1 HETEROTOPIAS AFTER PRENATAL TREATMENT WITH METHYLAZOXYMETHANOL IN RATS

Migration disorders cause neurons to differentiate in an abnormal hete rotopic position. Although significant insights have been gained into the etiology of these disorders, very little is known about the anatom y of heterotopias. We have studied heterotopic masses arising in the h ippocampal CA1 region after prenatal treatment with methylazoxymethano l (MAM) in rats. Heterotopic cells were phenotypically similar to neoc ortical supragranular neurons and exhibited the same temporal profile of migration and neurogenesis. However, they did not express molecules characteristic of CA1 neurons such as the limbic-associated membrane protein. Horseradish peroxidase injections in heterotopia demonstrated labeled fibers not only in the neocortex and white matter but also in the CA1 stratum radiatum and stratum lacunosum. To study the pathophy siological consequences of this connectivity, we compared the effects of neocortical and limbic seizures on the expression of Fos protein an d on cell death in MAM animals. After metrazol-induced seizures, Fos-p ositive cells were present in CA1 heterotopias, the only hippocampal r egion to be activated with the neocortex. By contrast, kainic acid-ind uced seizures caused a prominent delayed cell death in limbic regions and in CA1 heterotopias. Together, these results suggest that neocorti cal heterotopias in the CA1 region are integrated in both the hippocam pal and neocortical circuitry. J. Comp. Neurol. 394:520-536, 1998. (C) 1998 Wiley-Liss, Inc.