Role of afferents in the development and cell survival of the vertebrate nervous system.

1. During normal development of the vertebrate central nervous system, a considerable number of neurons die. The factors controlling which neurons die and which survive are not fully understood. 2. Target populations are known to maintain their innervating neurons. However, the role of afferents in maintaining their targets is still under review. 3. In the developing nervous system, deafferentation of a neuron population is difficult to achieve because plasticity (structural re-organization) can cause re-innervation of the area. Re-innervation alters, rather than removes, the afferent supply. 4. Afferent input is important for neuronal survival during development because deafferentation increases neuronal death by 20-30% and increasing input diminishes neuronal death. 5. Deafferented neurons die at the normal time for cell death for any given population. This occurs after the arrival of afferent axons but before the completion of connectivity and the onset of function. 6. Neuronal survival is maintained by any input, such as reinnervation by inappropriate fibres, but for optimal survival, morphological maturation and the acquisition of normal physiology, the correct input is required. 7. Afferents maintain their target neurons via a combination of electrical activity and delivery of trophic agents, which adjust intracellular calcium, thereby facilitating protein synthesis, mitochondrial function and suppressing apoptosis. 8. Evidence from animal and in vitro experiments indicates that afferents play an extremely important role in the survival of developing neurons in the immature vertebrate nervous system.