192-IGG-SAPORIN-INDUCED LOSS OF CHOLINERGIC NEURONS IN THE SEPTUM ABOLISHES CHOLINERGIC SPROUTING AFTER UNILATERAL ENTORHINAL LESION IN THERAT

After unilateral lesion of the entorhinal cotter, cholinergic septohip pocampal fibres are believed to sprout in the denervated outer molecul ar layer of the rat dentate gyrus. This cholinergic sprouting has been demonstrated by acetylcholinesterase (AChE) histochemistry, a method said selectively to label cholinergic septohippocampal fibres in the h ippocampus, However, a recent report has questioned this concept, sugg esting that AChE may not be an adequate marker to monitor cholinergic sprouting and that other, non-cholinergic axons sprouting after entorh inal cortex lesion cause the dense AChE-positive band in the denervate d outer molecular layer. In order to determine the contribution of cho linergic septohippocampal fibres to the dense AChE band appearing afte r entorhinal cortex lesion, the neurotoxin 192 IgG-saporin, known to d estroy cholinergic neurons in the basal forebrain selectively was used . Rats received bilateral injections of 192 IgG-saporin into the later al ventricles 3 weeks before entorhinal cortex lesion, simultaneously with entorhinal cortex lesion, or 8 weeks after entorhinal cortex lesi on. Immunocytochemistry for choline acetyltransferase (ChAT) and in si tu hybridization for ChAT mRNA demonstrated the loss of cholinergic ne urons in the medial septum and diagonal band after 192 IgG-saporin tre atment. The cholinergic sprouting response in the molecular layer, as visualized with AChE histochemistry, was abolished in all animals trea ted with immunotoxin. These data indicate that the dense AChE band for ming after entorhinal cortex lesion represents the sprouting of cholin ergic septohippocampal fibres.