Activity-dependent regulation of neuronal synthesis and release of neurite-promoting heparan sulfate proteoglycans.

Activity-dependent enduring change in neuronal communication is essential for exquisite connectivity during development of the nervous system and for adaptative responses of the mature nervous system. Here we report that glutamate activation of excitatory amino acid receptors induces the release of proteoglycans (PGs) with neurite growth-promoting activity from fetal hippocampal neurons in dissociated culture. Glutamate exposure produced an increase in the release of PGs of the heparan sulfate class but had no effect on the release of chondroitin sulfate PGs. PG release was mediated via both N-methyl-D-aspartate and metabotropic receptor activation. Conditions producing increased PG release also elicited a sustained increase in neuronal PG synthesis. These studies suggest that a class of substrate-bound growth modulatory glycoconjugates could participate in both the induction and maintenance of activity-dependent synaptic modification.