In the mammalian hippocampus, there is a trisynaptic loop that has been often referred to in studies on learning and memory mechanisms and their physiological correlate, the long-term potentiation (LTP). The three sets of synapses are formed by the fibers of perforant pathway terminating on granule cells and by the mossy fibers and Schaeffer collaterals making connections with the pyramidal cells. Each of the three types of synapses can develop LTP. LTP is accompanied by changes in gene expression and it is the nuclear transcription, involving specific transcription factors, that is the starting point for the series of biological amplifications and consolidations both necessary for such sustained changes. The transcription factors are proteins that control gene expression, development and functional formation in every eukaryotic cell. Two categories of transcription factors have been defined to date: general factors that comprise at least 20 proteins to form multiple preinitiation complex at the TATA box (TATA rich sequence) or regulatory factors that bind to promoter or enhancer regions at specific sites on the DNA close to, or distant from, the TATA box. Transcription factors have been divided into five different major classes according to unique protein motifs. These include basic domain, zinc-finger, helix-turn-helix, beta-Scaffold factors with minor groove contacts and other transcription factors not specifically classified. Much evidence has been accumulating in favor of the participation of several transcription factors in the consolidation of memory in the mammalian hippocampus following a spatial memory task. It is, therefore, of great importance that the involvement of transcription factors in de novo protein synthesis relevant to the synaptic mechanisms that mediate the formation of long-term memory should be summarized and discussed. No specific correlation between transduction of extracellular signals and expression of nuclear transcription factors, however, has been demonstrated to date.