EMBRYONIC NEURAL CELL-ADHESION MOLECULE (N-CAM) IS ELEVATED IN THE DENERVATED RAT DENTATE GYRUS

We evaluated the immunohistological changes in neural cell adhesion mo lecule (N-CAM) expression in the adult rat dentate gyrus during the pe riod of synaptic degeneration, axonal sprouting, and synaptogenesis fo llowing ipsilateral entorhinal cortex (ERC) lesion. This lesion denerv ates the outer two-thirds of the dentate granule cells dendrites and i nduces compensatory sprouting from the subjacent inner one-third into the denervated zone, as well as reactive synaptogenesis in the denerva ted outer molecular layer. In unlesioned adult hippocampus, antibodies to total N-CAM stained the inner molecular layer intensely, and the o uter molecular layer (ML) more lightly. After ERC lesion the intense s taining of the inner layer widened, the expansion following the known temporal sequence of commissural and associational (C/A) axon sproutin g into the denervated zone. In normal unlesioned controls there was ve ry light, uniform staining of the ML with antibodies directed against embryonic N-CAM (eN-CAM). By 2 d post-ERC lesion, the outer two-thirds of the ML stained robustly with antibody to eN-CAM. This area of inte nse staining receded as the C/A axon collaterals from the inner one-th ird entered the denervated zone, so that by 30 d the intense eN-CAM st aining only occupied the outer half of the ML. The increased expressio n of eN-CAM remained present at 60 d post-ERC lesion, past the point t hat synaptic volume density has returned to normal levels in the dener vated zone. Ultrastructural studies showed that the newly expressed eN -CAM was located on the surface of dendrites in the denervated zone, b ut was not found at the synaptic contacts. It was seen on the regenera ting axons as well. These studies allow us to compare temporal and spa tial correspondence between the expression of eN-CAM and the known seq uence of reactive synaptogenesis and axonal sprouting in the dentate g yrus. Our findings indicate that neural cell adhesion molecules are im portant in the dendritic response to sprouting and synaptic remodeling . Reexpression of eN-CAM in the denervated zone is an important compon ent of such axon-dendrite interactions in the CNS. Where reinnervation of the proximal dendritic field of the OML is by axons of the sprouti ng C/A afferents, eN-CAM is no longer expressed in the wake of the tra nslaminar expansion. The outer ML, which is reinnervated by other affe rents, maintains high levels of eN-CAM when reinnervation is complete. Thus, the source of the reinnervating axons determines the response o f the dendritic membrane of the target neurons.