The neurotrophic theory and naturally occurring motoneuron death.

There is increasing evidence that target-derived molecules play a crucial role in the regulation of neuronal survival during development. These molecules, termed neurotrophic factors, are thought to act in specific ways as defined by the neurotrophic theory. One central tenet of the neurotrophic theory is that some neurons in a population die because trophic molecules are available in only limited amounts during periods of naturally occurring cell death. Delivery of trophic factor to nerve terminals could be regulated by several mechanisms, including, for example, limited production (biosynthesis) by target cells, limited release by targets, or limited uptake by pre-synaptic terminals. An examination of recent studies of motoneuron development indicates that motoneurons compete, via axonal branching and synaptic contacts, for restricted sites on targets that provide access to trophic factors. According to this view, it is terminal branches and contact ('synaptic') sites that limit the regulation of neuronal survival, rather than trophic factor production.