LTP: A Personal Journey and Beyond

Long-term potentiation (LTP) has had a major impact on neuroscience. In this review I use LTP citations from PubMed and LTP publications from the Web of Science to analyze the fascinating history of research on LTP. Interest gradually grew from a prolonged delay after its discovery, to its meteoric rise and mature growth, and finally to a recent steep decline. While such rise and fall is not unique in science, the sharpness and magnitude of the swings in LTP are unusually dramatic. I discuss factors that contributed to each phase and point to key developments that led to the inflection points, at times using my own work as illustrations. I call attention to several factors that contributed to the decline in interest and conclude that LTP is to a great extent a victim of its own success. Much of the community now accepts that LTP and CaMKII are the cellular and molecular underpinning of memory. However, a broad shift toward "systems neurosciences" has deflected attention away from crucial cellular and molecular issues still unaddressed in LTP. This neglect is regrettable and unwarranted. Neuroscience doesn't have to choose between mechanisms and behavior, and I describe two somewhat overlooked examples where notable progress is being made in combining the two approaches. Countless exciting opportunities exist for further advances along these lines.