POSITIVE AND NEGATIVE REGULATORY MECHANISMS THAT MEDIATE LONG-TERM-MEMORY STORAGE

The protein kinase A pathway and the cyclic AMP-response element bindi ng protein (CREB) appear to play a critical role in the consolidation of short-term changes in neuronal activity into long-term memory stora ge 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 molecu lar machinery that mediates memory consolidation in each of these syst ems. One of the surprising findings to emerge, particularly from studi es of long-term facilitation in Aplysia, is that memory storage is med iated by not only positive but also negative regulatory mechanisms, in much the same way as cell division is controlled by the proteins enco ded by oncogenes and tumor suppressor genes. This suggests the interes ting possibility that there are memory suppressor genes whose protein products impede memory storage. (C) 1998 Elsevier Science B.V. All rig hts reserved.