Positive and negative regulatory mechanisms that mediate long-term memory storage

The protein kinase A pathway and the cyclic AMP-response element binding protein (CREB) appear to play a critical role in the consolidation of short-term changes in neuronal activity into long-term memory storage in a variety of systems ranging from the gill and siphon withdrawal reflex in Aplysia to olfactory conditioning in Drosophila to spatial and contextual learning in mice. In this review we describe the molecular machinery that mediates memory consolidation in each of these systems. One of the surprising findings to emerge, particularly from studies of long-term facilitation in Aplysia, is that memory storage is mediated by not only positive but also negative regulatory mechanisms, in much the same way as cell division is controlled by the proteins encoded by oncogenes and tumor suppressor genes. This suggests the interesting possibility that there are memory suppressor genes whose protein products impede memory storage.