Morphological deficits in noradrenergic neurons in GEPR-9s stem from abnormalities in both the locus coeruleus and its target tissues

The epileptic condition of the genetically epilepsy-prone rat (GEPR) appear s to be caused partially by deficiencies in the locus coeruleus (LC) innerv ation of the superior colliculus (SC). Previous studies provide quantitativ e documentation of noradrenergic morphological deficits in the moderately e pileptic GEPR-3. The present findings extend these studies by applying cell culture methodology to assessments of the severely epileptic GEPR-9, Our d ata show that total neurite length, the number of neurite branch points per cell, the cross-sectional area of cell bodies, and the cell perimeter are deficient in noradrenergic neurons in LC + SC cocultures derived exclusivel y from GEPR-9s compared to analogous cocultures obtained solely from nonepi leptic control rats. Partial restoration of LC neuron morphology toward nor mal occurs when the GEPR-9 SC component of the coculture is replaced with n onepileptic control SC. Finally, when the GEPR-9 SC is cocultured with the control LC, a partial morphological deficit occurs in the otherwise normal noradrenergic neurons. However, the magnitude of this deficit is less than that observed in noradrenergic neurons of the GEPR-9 LC cocultured with the control SC. These data support the hypothesis that the developmental defic iencies of noradrenergic neurons of the GEPR-9 are derived from two sources , the LC and its target tissue, in this case, the SC. Also, intrinsic abnor malities of the LC appear to make a more pronounced contribution to the nor adrenergic deficits than do those which reside in the SC. (C) 1999 Academic Press.