Models of neuronal death in vertebrate development: from trophic interactions to network roles

Clarke, P. G. H. (2003). In: Van Ooyen, A., ed. Modeling Neural Development. Cambridge, MA: MIT Press, pp. 167-182.

Abstract

Large numbers of neurons die in development at the time when their connections are being formed, and the survival of individual neurons during this period depends on their integrated response to anterograde signals received from their afferents as well as retrograde signals received from their efferent targets. In central neurons, both the anterograde and the retrograde signals are multiple. Both involve neurotrophic factors and both include a component dependent on electrical activity. The roles of the neuronal death are unclear, but the most widely invoked hypotheses involve the regulation of neuronal number or the refinement of connectivity.

While the signals controlling neuronal death appear to be moderately well understood, we have only a minimal conception of how they combine to affect the developing networks of the nervous system. To achieve such a network-level understanding, it will be necessary to incorporate the principles of neuron-to-neuron signaling into network-level models. The few models so far available are here reviewed and placed in their biological context.