Neuronal death in the central nervous system during development

About half the neurons in the brain die at the time when their connections are being formed. This neuronal death is regulated by anterograde and retro grade signals that reflect both electrical activity and the uptake of troph ic factors. Our recent data on the isthmo-optic projection indicate that th ere are in fact two different retrograde signals: a slow-acting survival si gnal mediated by a neurotrophin, and a fast-acting death signal mediated by calcium entry due to electrical activity in the presynaptic terminals. The developmental roles of the cell death are not well understood, but they ap pear to include the elimination of aberrant connections. The intracellular mechanisms of the cell death may nor always correspond to the apoptotic one s so thoroughly investigated in vitro, because only one of the three morpho logical types occurring regularly in vivo resembles apoptosis. However, our experiments on retinal ganglion cells indicate that several apoptotic mech anisms apply in this particular in vivo situation: these include an involve ment of oxygenated free radicals and glutathione, cell cycle-related events , and probably the synthesis of proteins promoting neuroprotection or cell death. (C) 1998 Elsevier, Paris.