7 14 20 25 30 Young adult Age (days)

Figure 9 Increases in axon density and in synaptic number in layer 1 of the developing rat cerebral cortex. •, synaptic number, parietal cortex; O, axon density, sensorimotor cortex (reproduced with permission of Elsevier Science and Cambridge University Press).

synthetic activity then increases enormously, 25 times the initial value, when the axons reach the connective and segmental nerves.

In the vertebrate CNS, the monoaminergic neurons develop very early during ontogeny and are among the first to differentiate, synthesize, store, and release their transmitter substances (dopamine, noradrenaline, or serotonin) long before the maturation of the brain region they innervate. These neurons are therefore thought to play important roles in neurotrophy and plasticity in the developing nervous system.

2. Mechanism of Synaptogenesis

Most of the structural synapses in the brain are formed within the early stage of life, e.g., during the first month after birth in rats and 1 or 2 years after birth in humans. However, determining the exact mechanism whereby the neurons in the developing nervous system form synapses remains a central challenge in neurobiology. Some neurons, such as those in the brain, do not project their axons very long before finding their appropriate synaptic partners. In other neurons, such as the motoneurons of the spinal cord, the axons traverse long distances to find and form synapses with the desired postsynaptic target membrane, bypassing all "inappropriate" membranes along the migration pathway. The question thus arises how the neurons distinguish appropriate from inappropriate

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