A role for immediate-early transcription factors in learning and memory

This article summarizes recent studies from the long-term potentiation (LTP), long-term depression (LTD), and behavioral learning literature, indicating that immediate-early genes (IEGs) may play an important role in learning and memory. The LTP studies suggest that synaptic modifications occurring during NMDA-receptor-mediated hippocampal LTP and LTD are stabilized by the protein products of the krox family of IEGs (as well as by brain-derived neurotrophic factor, BDNF). Activation of muscarinic receptors also induces members of the krox as well as the fos and jun family (jun-B but not c-jun) IEGs in hippocampal neurons and this action may be involved in the facilitatory effects of muscarinic receptor activation on both hippocampal LTP and learning. The possible role of IEGs in the learning-enhancing effects of cholinergically mediated hippocampal theta is also discussed. Finally, I review a number of recent studies showing IEG expression in brain neurons after behavioral learning. Together these results suggest some role for select IEGs (e.g., Krox 24) in learning and memory, although definitive studies using antisense DNA technology are required to establish any causal links. In particular, IEGs may be critical components of the signal transduction cascade that links NMDA and muscarinic receptors to the neuronal genome and ultimately to the generation of permanent modifications in neuronal biochemistry that provides the substrate for learning.