A COMPARISON OF BEHAVIORAL-EFFECTS AND MORPHOLOGICAL FEATURES OF GRAFTS RICH IN CHOLINERGIC NEURONS PLACED IN 2 SITES OF THE DENERVATED RATHIPPOCAMPUS

This study compared the morphological characteristics and the behaviou ral effects of intrahippocampal pal septal cell suspension grafts inje cted either just above the pyramidal cell layer of the hippocampal reg ion CA1 or within the dorsal leaf of the dentate gyrus (DG) in rats su bjected to electrolytic fimbria-fornix lesions. The behavioural tests determined home-cage and open-field activity, as well as radial-maze p erformance. Cresyl-violet staining, acetylcholinesterase (AChE) histoc hemistry. and parvalbumin. glial fibrillary acidic protein and glutami c acid decarboxylase immunocytochemistry were used for morphological a ssessments. The cross-sectional area of the grafts was measured betwee n 0.8 mm and 5.3 mm posterior to Bregma and used as an index of their development. Whether injected into CA1 or DG, the grafts provided the partially denervated hippocampus with a dense AChE-positive reinnervat ion. Both types of grafts were devoid of reactive astrocytes (although reactive astrocytes were found close to the graft-hose interface), co ntained almost no parvalbumin-positive neurons and showed a high densi ty of GAD-positive terminals. One of the main differences between the two groups of grafted rats was that the suspension injected into the D G yielded grafts that, in the vicinity of the injection sites (between 2.3 mm and 4.3 mm posterior to Bregma), had a cross-sectional area ex ceeding that of the grafts placed into CA1 by about 63-110% (average 7 9%), the latter being more dispersed than the former in the coronal pl ane. In addition, rats with grafts in the DG exhibited granule cell de generation in the vicinity of the injection sites, whereas rats with g rafts in region CA1 showed no damage near the injection sites. Concern ing the behavioural data, we found that fimbria-fornix lesions induced hyperactivity in both the home cage and the open field and impaired r adial-maze performance. Compared with the lesion-only rats, the grafte d rats in both groups had further increased open-field and home-cage a ctivity. While the grafts placed into region CA1 slightly, but signifi cantly, accentuated the lesion-induced deficit in radial-maze performa nce, those placed into the DG had no effect. These results suggest tha t intrahippocampal grafts, may, in some (still unspecified) conditions , produce adverse behavioural effects or no behavioural effects, despi te an acceptable graft-induced cholinergic reinnervation of the hippoc ampus. They do not allow a clear answer to the question of whether int ra-DG and intra-CA1 septal suspension grafts exhibiting almost compara ble morphological features (except in their size and their dispersion in the vicinity of the of the injection sites) induce behavioural effe cts that would depend on intrahippocampal location of the grafts. They suggest, however, that the granule cell degeneration caused by the im plantation procedure, in conjunction with the intragyral development o f the graft, probably does not account for some of the reported advers e behavioural effects of intrahippocampal basal forebrain grafts. Fina lly, the finding that septal cell suspensions placed into the DG yield ed larger grafts than when an equivalent number of cells was injected into CA1 might be explained by a larger lesion-induced neurotrophic ac tivity in DG than in region CA1, although both regions had undergone a similar degree of cholinergic denervation.