Transcription Factor Regulation In Brain: Focus on Activity and NMDA Dependent Regulation

Recent studies in invertebrate neurons indicate a role for rapid genomic responses in neurotransmitter induced synaptic plasticity (Montarolo et al. 1986). RNA and protein synthesis also appear critical for certain forms of neural plasticity in vertebrate systems (Agranoff 1989). These studies focus attention on the role of transmitter regulated gene expression in neuroplasticity. Neurotransmitters (Greenberg et al. 1986), growth factors (Lau and Nathans 1985; Milbrandt 1987) and neuroexcitatory stimuli (Morgan et al. 1987) rapidly induce genes that code for transcription regulatory proteins, demonstrating that cellular membrane events can rapidly regulate genomic function. Moreover, because transcription factors bind to DNA and regulate gene expression, these observations suggest that a regulated cascade of genomic events may be important in transmitter induced responses. To assess the postulated role of transcription factors in brain physiology, we have focused on identifying transcription factor genes that are rapidly induced in brain and on examining mechanisms involved in their regulation. We have identified a set of transcription factors that are regulated by synaptic activity and NMDA receptors and therefore may play a role in neuroplasticity.