Embryonic entorhinal transplants project selectively to the deafferented entorhinal zone of adult mouse hippocampi, as demonstrated by the use of Thy-1 allelic immunohistochemistry. Effect of timing of transplantation in relation to deafferentation

The mouse Thy-1.1/Thy-1.2 allelic marking system is used to show that transplanted embryonic entorhinal cortex can reinnervate adult host hippocampi. The projection is limited to the appropriate terminal zones--viz. the outer two-thirds of the stratum moleculare of the dentate gyrus, and the stratum lacunosum-moleculare of the hippocampus--and extends for up to about 2 mm into the denervated host terminal field. The reconstruction of the entorhinal projections to the host requires direct contact between the embryonic donor tissue and the denervated adult host terminal field, and is dependent upon removal of the ipsilateral host entorhinal area. In the absence of an overall deafferenting host entorhinal lesion the transplanted entorhinal area forms only small local projections which are confined to areas which would have been locally deafferented as a result of direct damage to the host entorhinal afferents (i.e. during their intrahippocampal course) by the hippocampal lesion caused at the time when the transplant was inserted. The correct relative timing of deafferentation and transplantation is vital for the formation of the transplant-to-host projection. The host dendrites can be made receptive to entorhinal transplant projections by removal of the host entorhinal area at the time of transplantation. When deafferentation is performed first and transplantation is delayed, it is found that the deafferented host dendrites retain this receptivity even when deafferentation has been performed as much as two months before transplantation. Reversing the order of transplantation and deafferentation, however, shows that the transplants have only a transient ability to project to the deafferented host territory. Thus, transplants inserted and allowed to become established for one week before host deafferentation make very much reduced projections to the host, and from two weeks onwards are incapable of any detectable response to subsequent removal of the host entorhinal area. Coextensive with the formation of transplant-to-host entorhinodentate projections, the host entorhinal lesion also induces an intensification of the acetylcholinesterase staining of the host septodentate afferents in the denervated outer dentate stratum moleculare. The findings demonstrate the accurate reconstruction of a lost projection in adult brain by transplanting the appropriate type of embryonic tissue, but the results of altering the relative timing of deafferentation and transplantation raise currently unsolved questions about the nature of the competitive interactions between transplant and host axons.(ABSTRACT TRUNCATED AT 400 WORDS)