ROLE FOR CELL-ADHESION AND GLYCOSYL (HNK-1 AND OLIGOMANNOSIDE) RECOGNITION IN THE SHARPENING OF THE REGENERATING RETINOTECTAL PROJECTION INGOLDFISH

Cell-adhesion molecules (CAMs) are thought to play crucial roles in de velopment and plasticity in the nervous system. This study tested for a role for cell adhesion and in particular, the recognition of two gly cosyl epitopes (HNK-1 and oligomannoside) in the activity-driven sharp ening of the retinotopic map formed by the regenerating retinal fibers of goldfish. HNK-1 is a prominent glycosyl epitope on many CAMs and e xtracellular matrix (ECM) molecules, including NCAM, LI, ependymin, an d integrins, which have all been implicated in synaptic plasticity. To test for a role of HNK-1 in the sharpening process, we used osmotic m inipumps to infuse HNK-1 antibodies for 7-21 days into the tectal vent ricle starting at 18 days after optic nerve crush. Retinotopic maps re corded at 76-86 days postcrush showed a lack of sharpening similar to that seen previously with two antibodies to ependymin, an HNK-1-positi ve ECM component present in cerebrospinal fluid. The multiunit recepti ve fields at each point averaged 26 degrees versus 11-12 degrees in re generates infused with control antibodies or Ringer's alone. The HNK-1 epitope also binds to the G2 domain of laminin to mediate neuron-ECM adhesion. To test for a role for laminin, a polyclonal antibody was si milarly infused and also prevented sharpening to approximately the sam e degree. The results support a role for the HNK-1 epitope and laminin in retinotectal sharpening. The oligomannoside epitope (recognized by monoclonal antibody L3) on the CAM L1 interacts with NCAM on the same cell to promote stronger L1 homophilic interactions between cells. Bo th an L1-like molecule and NCAM are prominently reexpressed in the reg enerating retinotectal system of fish. Infusion of oligomannosidic gly copeptides resulted in decreased sharpening, with multiunit receptive fields that averaged 22.7 degrees. Infusions of mannose-poor glycopept ides Less prominently disrupted sharpening, with average multiunit rec eptive fields of 18 degrees. Thus, oligomannosidic glycans in particul ar may play a role in retinotopic sharpening. Blocking glycan-mediated interactions between CAMs and ECM molecules could decrease the extent of exploratory growth of retinal axon collaterals, preventing them fr om finding their retinotopic sites, or could interfere with LI or NCAM and laminin binding at the synaptic densities preventing stabilizatio n of retinotopically appropriate synapses. Together, these results sup port a prominent role for cell adhesion and glycan epitopes in visual synaptic plasticity. (C) 1998 John Wiley & Sons, Inc.