In 1995 Bartsch found that there are in fact two forms of the CREB protein, much as the model of Jacob and Monod might have predicted: one that activates gene expression (CREB-1), and one that suppresses gene expression (CREB-2). Repeated stimulation causes protein kinase A and MAP kinase to move to the nucleus, where protein kinase A activates CREB-1 and MAP kinase inactivates CREB-2. Thus long-term facilitation of synaptic connections requires not only a switching on of some genes, but also the switching off of others (figure 19–1).
