Recent evidence suggests that cell surface receptor stimulation regulates expression of genes that may in turn be involved in long-term alterations of cellular behavior. To characterize synaptic mechanisms involved in regulating cellular immediate early genes (IEGs) in the brain, this chapter studies mRNA levels in hippocampal granule cells after excitatory stimulation via perforant path (pp) afferents. The pp-granule cell synapse has been extensively characterized because it demonstrates long-term potentiation of synaptic potentials following specific stimuli. This paradigm therefore provides the opportunity to examine the association of IEG activation with specific synaptic stimuli as well as with neuronal plasticity. The major findings of these studies are (1) IEG mRNA levels are dynamically regulated in the brain by neuron activating stimuli; (2) immediate early genes may be selectively regulated by specific stimuli; (3) synaptic NMDA receptor activation is involved in the rapid regulation of zif/268 mRNA levels by high-frequency pp stimuli; (4) convergent inhibitory synaptic inputs coordinately modulate LTP and zif/268 mRNA increases; and (5) the intensity of synaptic stimuli necessary to increase zif/268 mRNA levels is similar to that required to induce LTP.
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