Neuronal plasticity in the hippocampal formation after selective hippocampal cell destruction

Abstract

Deafferentation of septohippocampal projections result in an anomolous sprouting of noradrenergic fibers of peripheral sympathetic origin into the hippocampal formation. Ingrowth of these fibers is directed specifically into the dentate hilus, CA4 and CA3 hippocampal regions. Two particular cell populations are represented in these areas; granule cells in the dentate, and pyramidal cells in CA3 and CA4. Both zinc-dithiazone and noradrenergic histofluorescence staining show quantifiably significant differences after destruction of septohippocampal projections. The objective of the present study was to determine if selective elimination of specific hippocampal cell populations altered zinc-dithiazone and/or catacholamine glyoxylic acid fluorescence. Neurotoxins and electrolytic lesions of the septal nuclei were used to examine effects of cell destruction. Kainic acid (KA) eliminated pyramidal cells in CA3 and CA4. Colchicine selectively eliminated granule cells. Medial septal lesions were administered to eliminate septal projections to induce sympathetic sprouting. Microspectrophotometric quantification of noradrenergic histofluorescence intensity and zinc-dithiazone density showed significant differences between experimental groups. Results indicated a significant increase in zinc and fluorescence in rats receiving KA, septal lesions or combined KA and lesion. Zinc increases were transient, high at 10 days post lesion and returning to normal by 30 days. Colchicine treatment prohibited an increase in fluorescence and permanently lowered zinc density. These findings suggest granuale cells in the dentate are necessary for initiation of sympathetic ingrowth. Furthermore, elimination of CA3 and CA4 pyramidal cells with KA was sufficient to induce noradrenergic sprouting in the hippocampus without destruction of septohippocampal projections. Results were further discussed in relation to behavioral and neural recovery of function.