REQUIREMENT OF PROTEIN-SYNTHESIS FOR GROUP-I MGLUR-MEDIATED INDUCTIONOF EPILEPTIFORM DISCHARGES

Picrotoxin (50 mu M) elicited rhythmic synchronized bursting in CA3 py ramidal cells in guinea pig hippocampal slices. Addition of the select ive group I metabotropic glutamate receptor (mGluR) agonist (S)-3,5-di hydroxyphenylglycine (25 mu M) elicited an increase in burst frequency . This was soon followed by a slowly progressive increase in burst dur ation (BD), converting the brief 250-520 ms picrotoxin-induced synchro nized bursts into prolonged discharges of 1-5 s in duration. ED was si gnificantly increased within 60 min and reached a maximum after 2-2.5 h of agonist exposure. The protein synthesis inhibitors anisomycin (15 mu M) or cycloheximide (25 mu M) significantly impeded the mGluR-medi ated development of the prolonged bursts; 90-120 min of agonist applic ation failed to elicit the expected burst prolongation. By contrast, t he mGluR-mediated enhancement of burst frequency progressed unimpeded. Furthermore, protein synthesis inhibitors had no significant effect o n the frequency or duration of fully developed mGluR-induced prolonged discharges. These results suggest that the group I mGluR-mediated pro longation of synchronized bursts has a protein synthesis-dependent mec hanism.