THE POLYSIALIC ACID MODIFICATION OF THE NEURAL CELL-ADHESION MOLECULEIS INVOLVED IN SPATIAL-LEARNING AND HIPPOCAMPAL LONG-TERM POTENTIATION

The alpha-2,8-linked polysialic acid (PSA) modification of the neural cell adhesion molecule (NCAM) modulates morphogenetic cell interaction s. PSA is strongly expressed during neural development and generally d own-regulated in the adult, However, it remains prominent in some area s of the brain, e.g., the hippocampus. We assayed the functional role( s) of PSA in synaptic plasticity in the hippocampus in two experimenta l paradigms by removing PSA with endo-neuraminidase NE (endo-N) an enz yme which specifically cleaves alpha-2,8-linked polysialic acid. (1) T he acquisition and retention of spatial memory of rats in the Morris w ater maze, critically dependent on the hippocampus, was significantly impaired after a localized injection of endo-N into the hippocampus, w hereas visual and motor capacities were unaffected, (2) Tetanic stimul ation of the Schaffer collaterals in endo-N-treated hippocampal slices in vitro failed to elicit LTP and yielded only a short post-tetanic p otentiation, but the response returned to control levels within 2 minu tes, whereas basal synaptic activity and short-term potentiation were not affected. Our findings suggest that the carbohydrate epitope PSA p lays an important role in synaptic plasticity. (C) 1996 Wiley-Liss, In c.