Plasticity of neuronal connections in developing brains of mammals.

Although mature nervous systems show substantial malleability following various surgical or environmental manipulations, developing brains show far more prominent plasticity, particularly in terms of morphological features. Neuronal circuits, for example, can be dramatically rewired following neonatal but not adult brain lesions. It remains unknown why neuronal circuits in developing brains show such remarkable plasticity. A number of anatomical and physiological studies suggest that there are transient projections in developing brains and they are eliminated by cell death and/or collateral elimination as development proceeds. This raises a possibility that aberrant projections observed following various surgical or environmental manipulations such as partial denervation, results from retention or stabilization of transient projections. However, evidence suggests that cell death does not play an important role in developmental fine-tuning of neuronal projections. Furthermore, although the elimination of axon collaterals takes place, individual neurons appear to elaborate axonal arbors in appropriate target areas, resulting in a net increase in the size of axonal arbor emerging from individual neurons. In accord with these observations, the number of synapses appear to increase during the period when axonal elimination proceeds. Taken together, reinforcement of appropriate projections rather than elimination of excessive connections plays a major role in developmental specification of neuronal connections. Appearance of aberrant projections after partial denervation may not be a consequence of disordered axonal growth, since they form topographic maps which precisely mirrors those for normal projections. They may be induced due to reinforcement of pre-existing neuronal connections rather than to construction of novel pathways. Observations of axonal morphology in denervated areas indicate that lesion-induced enlargement of projections is due to transformation of axonal morphology, from simple and poorly branched to multiply branched. Perhaps such simple and poorly branched axons in inappropriate target areas may represent ones in the course of elimination but they may serve as a source of sprouting when denervated. In other words, after total elimination of axons any surgical or environmental manipulation cannot induce enlargement of projections. The mechanisms underlying such modifiability of neuronal connections remains unclarified but possible participation of an activity-dependent competitive mechanism is discussed.