Brain Research, 456 (1988) 193-198 193 Elsevier BRE 23004 Human fetal basal forebrain neurons grafted to the denervated rat hippocampus produce an organotypic cholinergic reinnervation pattern O.G. Nilsson 1, P. Brundin 1, H. Widner 2, R.E. Strecker 1 and A. Bj6rklund 1 IDepartment of Medical Cell Research, Section of Neurobiology, University of Lund, Lund (Sweden) and 2Department of Immunology, University of Stockholm, Stockholm (Sweden) (Accepted 12 April 1988) Key words: Neural transplantation; Human fetus; Septum; Hippocampus; Acetylcholinesterase; Immunization The septal/diagonal band (SDB) area, obtained from a 9- to 10-week-old aborted human fetus, was grafted to the hippocampal for- mation of adult, immunosuppressed rats subjected to an aspirative lesion of the fimbria-fornix. Nineteen weeks after transplantation, microscopical analysis revealed large, partly acetylcholinesterase (AChE)-positive grafts in the hippocampus in 3 of the 5 recipients. The AChE-positive grafts gave rise to a reinnervation of the host hippocampus and an AChE-positive lamination of the different hip- pocampal subfields with the same characteristics as the normal septum-derived innervation. Immunological evaluation of host sera re- vealed that all rats were immunized by the graft. This indicates that grafted human cholinergic SDB neurons can respond to or interact with factors that regulate and guide the innervation of the rat hippocampus. Intracerebral grafts of fetal neural tissue can estab- lish extensive efferent connections with previously denervated regions in the host brain. The innervation patterns produced by different kinds of grafted neu- rons has been shown to be different and specific for various types of neurons. In the rodent hippocampal formation, grafts of cholinergic septal tissue 3, norad- renergic locus coeruleus tissue 2'4, and serotonergic raphe tissue ~'l~'ls all give rise to characteristic inner- vation patterns of the deafferented hippocampal for- mation that mimic the normal innervations. Thus, using acetylcholinesterase (ACHE) histocbemistry to visualize cholinergic axons, it has been shown that syngeneic grafts of fetal septal/diagonal band (SDB) neurons placed directly in the deafferented rodent hippocampus reinnervate host hippocampal subfields with a largely normal laminated AChE-positive in- nervation pattern 3. Moreover, these AChE-positive grafts can form functional connections with the host hippocampus 11"IS. The ability to extensively inner- vate the hippocampus with a normal AChE-positive pattern has recently been shown to be partly specific for grafted SDB cholinergic neurons since grafts of other types of central cholinergic neurons either pro- dt~ce less innervation or give rise to an innervation pattern that is abnormal la. The ability of SDB neu- rons to reinnervate the hippocampus is at least to some extent also retained when they are xeno- grafted, as mouse basal forebrain tissue grafted to rat hippocampus both produces a normal innervation pattern and has functional effects s~9. Relatively little is known about the immunological characteristics of the brain and to what extent human fetal CNS tissue is immunogenic. We have recently found that human ventral mesencephalic tissue from aborted fetuses of 6.5-12 weeks post-conceptional ages grafted to the rat striatum is capable of eliciting an antibody pro- duction directed against human T-cell antigens 7. In the present experiment, we investigated wheth- er human cholinergic SDB neurons are able to sur- vive and reinnervate the rat hippocampus and wheth- er this donor tissue/target combination will immunize Correspondence: O.G. Nilsson, Department of Medical Cell Research, Section of Neurobiology, Biskopsgatan 5, S-223 62 Lund, Sweden. 0006-8993/88/$03.50 © 1988 Elsevier Science Publishers B.V. (Biomedical Division)