EFFECTS OF FETAL HIPPOCAMPAL FIELD GRAFTS ON ISCHEMIC-INDUCED DEFICITS IN SPATIAL NAVIGATION IN THE WATER MAZE

Transitory global cerebral ischaemia induced in rats by four vessel oc clusion for 15 min produced substantial loss of CA1 cells in dorsal hi ppocampus, and minimal damage in other intra- and extrahippocampal for ebrain regions examined. Ischaemic rats showed long-lasting deficits i n spatial navigation in the water-maze, consisting of impaired learnin g to locate a hidden platform in a novel pool, a substantial increase in time spent searching close to the platform without finding it, and moderate deficits in matching to position in a working memory task. Gr oups of ischaemic rats were implanted with fetal tissue dissected from hippocampal CA1 field, containing glutamatergic CA1 pyramidal cells, from dentate gyrus, containing glutamatergic dentate granule cells, an d from basal forebrain, containing cholinergic cells, with grafts site d in the alveus above the damaged CA1 region, for comparison with non- grafted ischaemic and non-ischaemic control groups, over a series of t ests from four to 20 weeks after grafting. All ischaemic groups showed comparable acquisition deficits prior to transplantation, and similar loss of CA1 cells on post mortem examination. When tested in a famili ar pool in retention and reversal learning of the original platform po sition, and a working memory task, all ischaemic rats performed better than in initial acquisition. However, rats receiving CA1 grafts showe d the most consistent improvement relative to ischaemic controls. When tested in a second (i.e. novel) pool, ischaemic rats again showed mar ked impairment, whereas rats with CA1 grafts were significantly superi or, and learned as rapidly as non-ischaemic controls. The performance of groups with dentate granule and basal forebrain grafts was similar to that of the non-grafted ischaemic control group throughout testing. These results suggest that ischaemic rats are impaired in the adaptiv e use of spatial information, as shown by acquisition and working memo ry deficits, but not in long- or short-term memory storage processes, and are also impaired in precise spatial localization. The effects of CA1 grafts in restoring spatial abilities, shown most clearly when rat s were tested in a novel environment, suggest that these grafts may ha ve assisted with repair to the damaged host circuit, rather than acted through the release of an appropriate neurotransmitter, since the glu tamatergic dentate granule grafts were ineffective. However, CA1 graft s showed better survival and growth than the other types of transplant , so that functional recovery may have been related to graft viability rather than to the specific type of graft.