ACTIVITY-DEPENDENT REGULATION OF NEURONAL SYNTHESIS AND RELEASE OF NEURITE-PROMOTING HEPARAN-SULFATE PROTEOGLYCANS

Activity-dependent enduring change in neuronal communication is essent ial for exquisite connectivity during development of the nervous syste m and for adaptive responses of the mature nervous system. Here we rep ort that glutamate activation of excitatory amino acid receptors induc es the release of proteoglycans (PGs) with neurite growth-promoting ac tivity from fetal hippocampal neurons in dissociated culture. Glutamat e exposure produced an increase in the release of PGs of the heparan s ulfate class but had no effect on the release of chondroitin sulfate P Gs. PG release was mediated via both N-methyl-D-aspartate and metabotr opic receptor activation. Conditions producing increased PG release al so elicited a sustained increase in neuronal PG synthesis. These studi es suggest that a class of substrate-bound growth modulatory glycoconj ugates could participate in both the induction and maintenance of acti vity-dependent synaptic modification. (C) 1994 Academic Press, Inc.