DIFFERENTIAL INDUCTION OF IMMEDIATE EARLY GENES BY EXCITATORY AMINO-ACID RECEPTOR TYPES IN PRIMARY CULTURES OF CORTICAL AND STRIATAL NEURONS

In primary cultures of neurons from cerebral cortex and striatum, 30 s stimulation with the excitatory amino acid glutamate elicited a 5 to 9-fold increase in immediate early gene (IEG) mRNAs. Glutamate increased c-fos, c-jun, jun-B, and NGFI-A (zif/268) mRNAs by binding to both alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor types, and increased c-fos, jun-B, and NGFI-A mRNAs by binding to the metabotropic receptor. NMDA receptor activation elicited IEG expression by a transmembrane calcium influx; AMPA receptor-induced depolarization played a permissive role for the opening of the NMDA receptor channel. The protein kinase C (PKC) inhibitor H-7 (but not inhibitors of cyclic nucleotide-dependent and calcium/calmodulin-dependent protein kinases) partially blocked IEG expression induced by glutamate.