Calcium regulation of neuronal gene expression

Plasticity is a remarkable feature of the brain, allowing neuronal structur e and function to accommodate to patterns of electrical activity. One compo nent of these long-term changes is the activity-driven induction of new gen e expression, which is required for both the long-lasting long-term potenti ation of synaptic transmission associated with learning and memory, and the activity-dependent survival events that help to shape and wire the brain d uring development. We have characterized molecular mechanisms by which neur onal membrane depolarization and subsequent calcium influx into the cytopla sm lead to the induction of new gene transcription. We have identified thre e points within this cascade of events where the specificity of genes induc ed by different types of stimuli can be regulated. By using the induction o f the gene that encodes brain-derived neurotrophic factor (BDNF) as a model , we have found that the ability of a calcium influx to induce transcriptio n of this gene is regulated by the route of calcium entry into the cell, by the pattern of phosphorylation induced on the transcription factor cAMP-re sponse element (CRE) binding protein (CREB), and by the complement of activ e transcription factors recruited to the BDNF promoter. These results refin e and expand the working model of activity-induced gene induction in the br ain, and help to explain how different types of neuronal stimuli can activa te distinct transcriptional responses.