Dual control by targets and afferents of developmental neuronal death in the mammalian central nervous system: A study in the parabigeminal nucleus of the rat

Natural and induced cell degeneration were studied in the mesencephalic parabigeminal nucleus of postnatally developing rats. Natural cell death in the normal parabigeminal nucleus had already started at birth, was maximal at 3 days, and proceeded with a declining rate until postnatal days 8–10 in the dorsal, middle, and ventral divisions that compose the nucleus. The number of neurons declined by approximately one‐third between birth and postnatal day 15. A unilateral lesion of the superior colliculus made at birth modified this pattern. In the deafferented ipsilateral middle division, the rate of cell death was above normal from day 1 to day 10, and the number of neurons at day 15 was 60% less than in unoperated controls. In the contralateral middle division, in which at least some of the neurons were axotomized by the lesion, the rate of cell death increased at days 1–2 and decreased below normal at days 3–5. Induced changes in the number of neurons were consistent with this pattern, and at day 15 the number was similar to the control value. In the ipsilateral dorsal and ventral divisions, which suffered simultaneous axotmy and deafferentation, the rate of cell death increased in 2 peaks at days 1–2 and 4–6, and the numbers of neurons dropped to negligible values at day 15. The frequency curves of degenerating cells were poor predictors of the absolute changes in neuron numbers, and evidence was found of continued postnatal migration of neurons into the developing parabigeminal nucleus. This study indicated that retrograde and anterograde degeneration cotemporal with natural cell death in the developing parabigeminal nucleus proceed with distinct time courses and interact when induced simultaneously. The nucleus regulates through a reduction in the rate of cell death after an early depletion of neurons caused by axotomy, as long as the tectal input remains intact. The results support the hypothesis that the afferent supply, as well as the integrity of axons, have major roles in the control of neuronal survival in the developing brain.