Stability of septohippocampal neurons following excitotoxic lesions of the rat hippocampus.

The present study examined the effects of removing hippocampal nerve growth factor (NGF)-producing neurons upon cholinergic and noncholinergic septohippocampal projecting neurons. To deplete septal/diagonal band neurons of their intrinsic source of NGF, rats received unilateral intrahippocampal injections of ibotenic acid and were sacrificed 2-24 weeks later. Choline acetyltransferase and parvalbumin immunohistochemistry failed to reveal changes in the number of cholinergic or gamma-aminobutyric acid-containing neurons, respectively, within the septal/diagonal band region ipsilateral to the hippocampal lesion at any time point examined. Additionally, immunocytochemical localization of nonphosphorylated and phosphorylated neurofilament proteins did not reveal abnormal staining characteristics within the septal/diagonal band complex, suggesting that this lesion does not alter cytoskeletal features of neurons which project to the hippocampus. Selected rats received unilateral hippocampal lesions and 3 months later were injected with fluorogold into the remaining hippocampal remnant and with wheat germ agglutinin conjugated to horse radish peroxidase into the intact contralateral hippocampus. Both retrograde tracers were predominantly transported to their respective ipsilateral septum and vertical limb of the diagonal band. This indicates that following the lesion, septal/diagonal band neurons still project ipsilaterally and sprouting to the NGF-rich contralateral side does not occur. RNA blot analysis revealed a decrease in NGF mRNA expression within the lesioned hippocampus with a maximum reduction of approximately 70%. In contrast, no change in NGF mRNA expression was observed within the ipsilateral septum relative to the contralateral side. The present study demonstrates that removal of hippocampal target neurons does not alter the number, morphology, or projections of both cholinergic and noncholinergic septal/diagonal band neurons.