Time course of increases in retrograde labeling and increases in cell size of entorhinal cortex neurons sprouting in response to unilateral entorhinal lesions
Authors: Goldschmidt Richard B. , Steward Oswald 
Published: January 2005

Unilateral lesions of the entorhinal cortex in adult rats induce sprouting of the projections from the surviving contralateral entorhinal area to the denervated fascia dentata. In animals with long‐standing lesions, the cells in the surviving entorhinal area exhibit increased transport of HRP following injections into the reinnervated fascia dentata, and the labeled cells which participate in the reinnervation are larger than unlabeled cells which do not give rise to reinnervating fibers. In the present study, we examine whether these changes in retrograde labeling and cell size occur during the period in which sprouting is known to occur. HRP injections were placed in the fascia dentata in normal animals, and in animals which had received unilateral lesions of the ipsilateral entorhinal area 2, 4, 6, 8, 10, 14, or 20 days, and over 1 year previously. For each post‐lesion interval, animals survived for 2 days post‐injection. Labeled cells in layer II of the surviving contralateral entorhinal area were counted at a standard dorso‐ventral level from the best labeled cases at each survival interval. In addition, the size of the labeled cells was compared with the size of the nearest unlabeled cell in the same lamina from a larger sample of cases.

When animals were killed 4 days following unilateral entorhinal lesions (2 days post‐injection) no changes in the number of labeled cells in layer II were observed, in comparison to normal animals. Animals which had received HRP injections 4 days post‐lesion and which were sacrificed on the 6th post‐lesion day exhibited small increases in the number of labeled cells in layer II, and these increases became even more prominent in cases sacrificed on the 8th day post‐lesion. No further increases i the number of labeled cells were observed in cases sacrificed from 10 days to over 1 year post‐lesion.

Measurements of cell size in the entorhinal cortex indicated that in normal animals and in animals sacrificed from 4–6 days post‐lesion, the labeled cells in layer II were no larger than their unlabeled neighbors. However, the size of all cells in operated animals was less than in normal animals. In cases sacrificed 8 days post‐lesion, however, the labeled cells were an average of 28% larger than their unlabeled neighbors, and in cases sacrificed at longer post‐lesion intervals, this increase was maintained, although the percentage increase at later intervals was slightly smaller, ranging around 16% over control values. Because the timing of the increases in retrograde labeling and the relative increases in cell size correspond well with the time course of sprouting of this system measured autoradiographically, we conclude that these cellular changes are related to the proliferation of axon terminals within the denervated fascia dentata. The decrease in the size of all cells in layer II in the operated animals may be a result of the denervation of these cells through a loss of commissural projections from the contralateral entorhinal area.