Background

Since the earliest days of neurobiology, the study of neuronal cell death has been a field full of surprises. For example, the very contention that the death of neurons might be a normal part of the developmental program of the brain was greeted initially with great skepticism, and its formal demonstration by Hamburger (1975) and others came as quite a surprise to most workers in the field. Later, after the existence of target-related cell death and its dependence on trophic support had been firmly established, Oppenheim and colleagues uncovered yet another surprise. They showed that blocking neuronal activity during the critical period of a neuron, rather than mimicking the effects of target deprivation as expected, actually spared the doomed neurons from the fate of death (Pittman and Oppenheim, 1979). It is in this long tradition of surprises that we review a series of discoveries relating instances of neuronal cell death to a process normally linked to birth and regeneration: the cell cycle. By this time, however, the existence of a paradox such as this should come as no surprise.