A biochemical blueprint for long-term memory

The greatest barrier to the long-term storage of information in a biologica l system is the inevitability of molecular turnover. In this review, we dis cuss the features required of any chemical mechanism capable of overcoming this obstacle, positing that a specific type of "mnemogenic", or memory-for ming, chemical reaction is the basis of the engram. We describe how molecul es as diverse as protein kinases, prions, and transcription factors can par ticipate in mnemogenic reactions, and outline a blueprint for memory that p ostulates mnemogenic reactions at the synapse and in the nucleus and consid ers the constraints imposed by requirements for high fidelity and the abili ty to forget. This sort of a priori analysis may facilitate directed experi mental approaches to understanding the mechanisms of lifelong memory.