Pattern of long-distance projections from fetal hippocampal field CA3 and CA1 cell grafts in lesioned CA3 of adult hippocampus follows intrinsic character of respective donor cells

Fetal hippocampal grafts transplanted to the lesioned CA3 of adult hippocam pus can extend axonal projections to many regions of the host brain. Howeve r, the identity of grafted cells that project to specific host regions is u nknown. We hypothesize that the pattern of long-distance axonal projections from distinct fetal hippocampal cells grafted to lesioned CA3 is specified by the intrinsic nature of respective donor cells rather than characterist ics of the host graft region. We grafted fetal hippocampal CA3 or CA1 cells into kainic acid lesioned CA3 of adult hippocampus at four days post-lesio n. Neurons projecting to either the contralateral hippocampus or the ipsila teral septum were then measured in these grafts at four months post-graftin g using Fluoro-Gold and DiI tract tracing. CA3 grafts located close to the degenerated CA3 cell layer showed a high propensity for establishing projec tions into the contralateral hippocampus (commissural projections) compared to similarly located CA1 grafts, which exhibited negligible commissural pr ojections. Similar distinction was observed between the two graft types eve n when they were located only partially in the lesioned CA3. Among CA3 graf ts, those placed near the degenerated CA3 cell layer established significan tly greater commissural projections than those placed only partially in the CA3 region. Septal projections, in contrast, were robust from both CA3 and CA1 grafts. This differential projection pattern between CA3 and CA1 graft s resembles projections of CA3 and CA1 cells in intact hippocampus. These results demonstrate that the intrinsic character of grafted fetal cel ls determines the type of efferent projections from fetal grafts into diffe rent targets in the lesioned adult host brain. However, the extent of effer ent projections from specific grafts is also influenced by the location of grafted cells within the host region. Thus, graft-mediated appropriate reco nstruction of damaged circuitry in the lesioned brain may require grafting of homotopic donor cells. Further, the robust and specific projections obse rved from CA3 grafts is likely beneficial for functional recovery of hippoc ampus following CA3 injury and hence of significance towards developing a g raft-mediated therapy for human temporal lobe epilepsy. (C) 2000 IBRO. Publ ished by Elsevier Science Ltd. All rights reserved.