LESIONS OF SUPRACALLOSAL OR INFRACALLOSAL HIPPOCAMPAL PATHWAYS IN THERAT - BEHAVIORAL, NEUROCHEMICAL, AND HISTOCHEMICAL EFFECTS

Long-term behavioral and neurochemical effects of bilateral lesions to only the infracallosal component of the ''so-called'' septohippocampa l pathways (cingular bundle, fimbria and fornix) have not been assesse d. This experiment compared the behavioral, histochemical and neuroche mical effects of supracallosal (SUPRA; cingular bundle) and infracallo sal (INFRA; fimbria-fornix) hippocampal denervations in Long-Evans fem ale rats. The rats were tested, over two periods (8-52 and 92-170 days postlesion), for open field locomotion, spontaneous alternation and r adial-maze performance. Subsequently, histochemical or neurochemical d eterminations of cholinergic, serotonergic and noradrenergic hippocamp al innervations were performed using acetylcholinesterase-staining, de termination of high-affinity synaptosomal uptake of choline and seroto nin, and measurement of hippocampal serotonin and noradrenaline concen trations by HPLC methods. Whatever behavioral test was considered, no significant effect was found in rats with SUPRA lesions, whereas rats with INFRA lesions were permanently impaired in all tests. Histochemic al and neurochemical analyses showed hippocampal cholinergic as well a s serotonergic markers to be substantially decreased in INFRA rats as compared to SHAM and SUPRA rats. The SUPRA rats exhibited a weak but s ignificant reduction of both serotonergic and noradrenergic markers co mpared to SHAM and INFRA rats. These results suggest that lesions limi ted to the infracallosal pathway induce a hippocampal denervation suff icient to account for most of the behavioral, histochemical and neuroc hemical deficits classically reported following extensive lesions of t he anterior hippocampal connections. Since the behavioral and neuroche mical deficits were found to be lasting, it is suggested that bilatera l infracallosal damage to the septohippocampal pathways might constitu te an interesting paradigm of partial hippocampal deafferentation to i nvestigate the effects of neural grafts or other treatments in an anim al model of Alzheimer's disease. (C) 1994 Academic Press, Inc.