Immediate early gene transcription and synaptic modulation

Long-term changes in gene expression appear to be critical to the formation of memory, but little is known about its stimulus- transcription coupling. Numerous studies in the last decade, by focusing on unraveling this signal transduction pathway, have investigated the potential role of the immediat e-early genes in this process. The krox family of immediate-early gene prot eins are of particular interest because they may be involved in stabilizing the synaptic modifications that underlie hippocampal long-term potentiatio n (LTP), A potential upstream mediator of krox induction is cyclic AMP-resp onsive element binding protein (CREB), a posttranslationally activated tran scription factor that has been implicated in numerous memory paradigms. In this study we investigated whether the activation of CREB by phosphorylatio n may have a role in the development of rat perforant- path-stimulated LTP and associated dentate granule cell krox-24 mRNA expression. Contrary to wh at was expected, we failed to show any difference in the levels of phosphor ylated CREB after LTP or following endogenous synaptic facilitation stimula ted by novelty. Using these same model systems we also investigated the pro tein levels of brain- derived neurotrophic factor (BDNF), another immediate -early gene that is induced following a durable form of LTP. However, BDNF protein was not induced within the hippocampus after LTP and was transientl y decreased following novel environmental stimulation. (C) 1999 Wiley-Liss, Inc.