ALTERNATE STRATEGIES IN LESION-INDUCED REACTIVE SYNAPTOGENESIS - DIFFERENTIAL EXPRESSION OF L1 IN 2 POPULATIONS OF SPROUTING AXONS

In the CNS the cell adhesion molecule L1 plays a role in axonal growth and fasciculation. Since its roles in synapse formation and CNS regen eration are unknown, we followed the staining of L1 through the sequen ce of degeneration and reactive axon sprouting in the denervated outer molecular layer (ML) of the hippocampal dentate gyrus following ipsil ateral entorhinal cortex (ERC) lesion. We compared immunohistological and ultrastructural localization of L1 and employed image analysis to evaluate lamina-specific changes over time. L1 staining was uniformly distributed over the ML in unlesioned animals. Following ERC lesion, L 1 staining markedly declined in the outer ML; L1 staining in the inner ML remained constant. Over 30 days postlesion, commissural and associ ational (CIA) afferents from inner ML sprouted partway into the denerv ated zone, and L1 was expressed on these sprouting afferents. L1 stain ing exactly corresponded to fiber outgrowth as assessed by Holmes fibe r stain. As the L1-bearing axons of the C/A projection expanded, stain ing for embryonic N-CAM (reexpressed on the dendrites of the denervate d zone) appeared to recede. There was never overlap of L1 and embryoni c N-CAM staining; the difference always marked the boundary between in ner and outer ML. Ultrastructural analysis confirmed localization of L 1 staining to axonal profiles, indicating that the new pattern of L1 s taining reflected distinct types of axonal growth. These changes in ce ll adhesion molecule expression closely paralleled the known sequence of reactive synaptogenesis and axonal sprouting and demonstrate a link between cell adhesion molecule expression and axonal sprouting during self-repair by the CNS. (C) 1995 Academic Press,Inc.