THE FIMBRIA-FORNIX CINGULAR BUNDLE PATHWAYS - A REVIEW OF NEUROCHEMICAL AND BEHAVIORAL-APPROACHES USING LESIONS AND TRANSPLANTATION TECHNIQUES

Extensive lesions of the fimbria-fornix pathways and the cingular bund le deprive the hippocampus of a substantial part of its cholinergic, n oradrenergic and serotonergic afferents and, among several other behav ioural alterations, induce lasting impairment of spatial learning and memory capabilities. After a brief presentation of the neuroanatomical organization of the hippocampus and the connections relevant to the t opic of this article, studies which have contributed to characterize t he neurochemical and behavioural aspects of the fimbria-fornix lesion ''syndrome'' with lesion techniques differing by the extent, the locat ion or the specificity of the damage produced, are reviewed. Furthermo re, several compensatory changes that may occur as a reaction to hippo campal denervation (sprouting, changes in receptor sensitivity and mod ifications of neurotransmitter turnover in spared fibres) are describe d and discussed in relation with their capacity (or incapacity) to fos ter recovery from the lesion-induced deficits. According to this backg round, experiments using intrahippocampal or ''parahippocampal'' graft s to substitute for missing cholinergic, noradrenergic or serotonergic afferents are considered according to whether the reported findings c oncern neurochemical and/or behavioural effects. Taken together, these experiments suggest that appropriately chosen fetal neurons (or other cells such as, for instance, genetically-modified fibroblasts) implan ted into or close to the denervated hippocampus may substitute, at lea st partially, for missing hippocampal afferents with a neurochemical s pecificity that closely depends on the neurochemical identity of the g rafted neurons. Thereby, such grafts are able not only to restore some functions as they can be detected locally, namely within the hippocam pus, but also to attenuate some of the behavioural (and other types of ) disturbances resulting from the lesions. In some respects, also thes e graft-induced behavioural effects might be considered as occurring w ith a neurochemically-defined specificity. Nevertheless, if a graft-in duced recovery of neurochemical markers in the hippocampus seems to be a prerequisite for also behavioural recovery to be observed, this neu rochemical recovery is neither the one and only condition for behaviou ral effects to be expressed, nor is it the one and only mechanism to a ccount for the latter effects. (C) 1997 Elsevier Science Ltd.