Traumatic Lesions and Transplants of Granule Cells in the Dentate Gyrus Alter the Distribution of Afferent Fibers in the Molecular Layer

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Abstract
The present experiments determined whether traumatic lesions of the dentate gyrus granule cells had a different effect on the afferents in the molecular layer (ML) than nontraumatic lesions. Nontraumatic lesions of the granule cells induced by colchicine, ibotenic acid, x-radiation, and adrenalectomy have been reported to reduce both the acetylcholinesterase (AChE)-positive fibers and entorhinal afferents in the ML. After the nontraumatic granule cell lesions, the laminar distribution of the entorhinal afferents was maintained in the ML, whereas the AChE laminar pattern was lost. In the present study, dentate granule cells were traumatically lesioned by a fluid injection into the infragranular cleavage plane (IGCP) of the dentate gyrus. The traumatic lesion resulted in an altered distribution of the afferents in the ML. The perforant path fibers, shown by injection of wheat germ agglutinin horseradish peroxidase into the entorhinal cortex, occupied a greater proportion of the ML in lesioned animals than in control animals. The normal laminar pattern of AChE-positive afferents was not present after the granule cell lesion. There was an initial increase in AChE-positive fibers in the ML that lasted several weeks but eventually returned to near normal levels. The altered distribution of afferents could in part be due to uneven shrinkage of the molecular layer and/or sprouting of the afferents. Granule cell suspension transplants into the IGCP also traumatically lesioned the host granule cells but immediately replaced the damaged host granule cells with immature granule cells. The distribution of afferents was similar to that found in lesioned-only animals. The traumatic lesion induced MAP2 immunoreactivity in the anisomorphic reactive astrocytes of the ML. At the longer survival times, MAP2 was not seen in either the astrocytes of the ML or in the isomorphic reactive astrocytes in CA3.