CHOLINERGIC LESIONS BY 192-IGG-SAPORIN AND SHORT-TERM RECOGNITION MEMORY - ROLE OF THE SEPTOHIPPOCAMPAL PROJECTION

Two experiments examined the effects of cholinergic basal forebrain le sions by intraventricular and intrahippocampal infusions of the immuno toxin 192 IgG-saporin on recognition memory in an operant delayed-non- matching-to-position task in rats. Intraventricular infusions produced extensive reductions in cortical and hippocampal choline acetyltransf erase activity In the first experiment. Behaviourally, a mixed delay-d ependent/independent accuracy deficit and increased biased responding was observed post-lesioning. Thus, both mnemonic as well as non-mnemon ic processes were affected by the lesion. This performance deficit was indistinguishable from the impairment induced by acute intraventricul ar injections of the choline uptake inhibitor hemicholinium-3, which s uggests that cholinergic damage induced by 192 IgG-saporin disrupted p erformance, In the second experiment more discrete intrahippocampal 19 2 IgG-saporin: lesions were made, which reduced hippocampal choline ac etyltransferase activity about 57%, although this reduction was not as extensive as following intraventricular injections. Although intrahip pocampal lesions also impaired non-matching accuracy, this effect fail ed to reach significance during most stages of the experiment. Scopola mine just failed to significantly impair (P = 0.053) performance in hi ppocampal lesioned rats more than in controls. The nicotinic antagonis t mecamylamine did not affect the lesion-induced changes in performanc e. These results suggest that the cholinergic basal forebrain, includi ng the septohippocampal system, is important for the mediation of reco gnition memory, and muscarinic receptor-mediated mechanisms may be of greater importance than alterations pf nicotinic receptor-mediated pro cesses in the septohippocampal system.