Cell surface expression of polysialic acid on NCAM is a prerequisite for activity-dependent morphological neuronal and glial plasticity

Polysialic acid (PSA) on the extracellular domain of the neural cell adhesi on molecule (NCAM) reduces cell adhesion and is considered an important reg ulator of cell surface interactions. The hypothalamo-neurohypophysial syste m (HNS), whose glia, neurons, and synapses undergo striking, reversible mor phological changes in response to physiological stimulation, expresses high levels of PSA-NCAM throughout life. Light and electron microscopic immunoc ytochemistry in normal rats and rats in which cell transport was blocked wi th colchicine showed that PSA-NCAM is expressed in both HNS neurons and gli a, particularly at the level of astrocytic processes that envelop neuronal profiles and can undergo remodeling. Moreover, we confirmed that the overal l levels of PSA-NCAM were not greatly altered by stimulation (lactation and chronic salt ingestion). Nevertheless, PSA is essential to morphological p lasticity. Using comparative ultrastructural analysis, we found that, after specific enzymatic removal of PSA from NCAM by microinjection of endoneura minidase close to the hypothalamic magnocellular nuclei in vivo, there was no apparent withdrawal of astrocytic processes nor any increase in synaptic contacts normally induced by lactation and dehydration. Our observations d emonstrate, therefore, that expression of PSA on cell surfaces in the adult HNS is indispensable to its capacity for activity-dependent morphological neuronal-glial and synaptic plasticity. The carbohydrate PSA on NCAM can th us be considered a necessary permissive factor to allow neuronal and glial remodeling to occur whenever the proper inductive stimulus intervenes.