Xenografts of mouse hippocampal tissue. Exchange of laminar and neuropeptide specific nerve connections with the host rat brain.

Immature hippocampal and fascia dentata tissue from embryonic and newborn C57 mice was grafted to the hippocampal region of newborn Kyoto rats. The age of the donor mice varied from embryonic day 13 to the day of birth, and the recipient rats from the day of birth up to 2 days. After survival times of from 5 weeks to 1 year the recipient brains were histologically processed for the tracing of host-xenograft connections by silver staining and electron microscopy of anterograde degeneration, AChE histochemistry, immunohistochemical demonstration of the neuropeptides CCK and enkephalin, and the histochemical Timm sulphide silver method, as well as stained by ordinary cell and fiber stains. The survival of the xenografts depended on the donor age, with less than 10% survival for newborn donors and 60-69% for E13-16 donors. The surviving xenografts developed an organotypic organization and retained a mouse-specific CCK-reactivity in the associational hilodentate system and the dentate mossy fibers. Judged by their positive AChE histochemistry most xenografts received a host rat cholinergic projection when placed in normal cholinoreceptive areas, including areas outside the normal reach of the septo-hippocampal system like the neocortex. Xenografts encroaching on the trajectory of the host rat commissural and perforant path projections or their terminal fields in fascia dentata received laminar and neuropeptide specific host projections. Electron microscopy of host rat perforant path fibers traced to the xenograft dentate molecular layer confirmed the laminar distribution and revealed numerous asymmetric synaptic contacts with spines. An efferent xenograft projection of CCK-reactive mouse mossy fibers into the host CA3 mossy fiber layer demonstrated that this cross-species, mouse to rat innervation also applied to the normal developmental rules, despite the, for the rat abnormal, CCK-content. The formation of laminar and neuropeptide specific mouse-rat nerve connections demonstrates the potentials of intracerebral neuronal grafting in basic and applied neurobiological research by providing new experimental models for the analysis of developmental and functional interactions between nerve cells.