RAPID COMMUNICATION Requirement of Protein Synthesis for Group I mGluR-Mediated Induction of Epileptiform Discharges

Merlin, Lisa R., Peter J. Bergold, and Robert K. S. Wong. group I mGluR-mediated prolonged epileptiform discharges Requirement of protein synthesis for group I mGluR-mediated inin vitro as well (Merlin and Wong 1997b; Taylor et al. duction of epileptiform discharges. J. Neurophysiol. 80: 989–993, 1995). Furthermore, our data suggest that group I mGluR 1998. Picrotoxin (50 mM) elicited rhythmic synchronized bursting activation has epileptogenic properties: transient mGluR acin CA3 pyramidal cells in guinea pig hippocampal slices. Addition tivation results in persistent epileptiform activity, with longof the selective group I metabotropic glutamate receptor (mGluR) term autopotentiation of the group I mGluR response accomagonist (S)-3,5-dihydroxyphenylglycine (25 mM) elicited an inpanying this modification (Merlin and Wong 1997b). In the crease in burst frequency. This was soon followed by a slowly following studies we address whether the induction and/ progressive increase in burst duration (BD), converting the brief or maintenance of the epileptiform activities produced via 250–520 ms picrotoxin-induced synchronized bursts into prolonged discharges of 1–5 s in duration. BD was significantly inmGluR activation requires active protein synthesis. If the creased within 60 min and reached a maximum after 2–2.5 h of process is protein synthesis dependent, it would further supagonist exposure. The protein synthesis inhibitors anisomycin (15 port the conclusion that group I mGluR activation initiates mM) or cycloheximide (25 mM) significantly impeded the mGluRan enduring epileptogenic process. Portions of this work mediated development of the prolonged bursts; 90–120 min of have appeared in abstract form (Merlin and Wong 1997a). agonist application failed to elicit the expected burst prolongation. By contrast, the mGluR-mediated enhancement of burst frequency M E T H O D S progressed unimpeded. Furthermore, protein synthesis inhibitors had no significant effect on the frequency or duration of fully Guinea pigs 2–4 wk of age were anesthetized with halothane and decapitated in conformance with the recommendations of the developed mGluR-induced prolonged discharges. These results suggest that the group I mGluR-mediated prolongation of synchroGuide for the Humane Care and Use of Animals . The brain was rapidly removed and placed in ice-cold artificial cerebrospinal fluid nized bursts has a protein synthesis-dependent mechanism. (ACSF) containing (in mM) 124 NaCl, 26 NaHCO3, 5 KCl, 1.6 MgCl2 , 2 CaCl2 , and 10 D-glucose. Transverse hippocampal slices (400 mm) were prepared with the use of a Vibratome (Technical I N T R O D U C T I O N