Identification of the cells of origin of a central pathway which sprouts following lesions in mature rats.

Following unilateral destruction of the entorhinal cortical region of the adult rat, the denervated granule cells of the dentate gyrus are reinnervated as a result of the proliferation of a pathway from the surviving contralateral entorhinal area. The present study investigates the cells of origin of this lesion-induced pathway. Following HRP injections into the reinnervated dentate gyrus, heavily labeled cells were evident in layers II and III of the contralateral entorhinal area, in marked contrast to the pattern of labeling in normal animals, where labeled cells are restricted almost entirely to layer III. The atypically labeled cells in the operated animals were found predominantly in the dorsal half of the entorhinal area, and were concentrated in the medial most portion of layer II. These atypically labeled cells in layer II of the operated animals were an average of 16% larger than their unlabeled neighbors in the same lamina. This was not related to the loading with HRP, however, since in normal animals, cells in layer II which are labeled with HRP were no different in size than unlabeled cells. The atypically labeled cells in layer II of operated animals could also be identified at the electron microscopic level, and could be distinguished from the cells in layer III which normally project to regio superior of the contralateral hippocampal formation. While labeled cells were evident in layers II and III following injections into the reinnervated dentate gyrus, no labeled cells were found in the presubiculum or parasubiculum. In combination, these results suggest (1) the pathway which reinnervates the dentate gyrus from the contralateral entorhinal area originates predominantly, if not exclusively, from the cells in layer II, (2) these cells in layer II have the same preferential distribution within the entorhinal area as the rare lightly labeled cells which can be found contralateral to an injection in normal animals and (3) cells which participate in the reinnervation are larger than their unlabeled neighbors which presumably do not give rise to fibers which reinnervate the contralateral dentate gyrus. Since the cells in layer II which sprout following lesions can be identified at both the light and elctron microscopic level, a potentially valuable model system is available in which to analyze cellular changes during sprouting.