The serotonin innervation of the basal forebrain shows a transient phase during development

The serotonergic innervation of the adult and developing basal forebrain nuclei of the rat was studied with immunocytochemical techniques at the light and electron microscopic levels. A substantial number of relatively thick serotonergic fibers with few varicosities and random orientation were observed at the time of birth. During the subsequent weeks, the serotonergic fibers increased in number and became thinner with many varicosities. They were also re-oriented, and around the end of the third postnatal week they exhibited the pattern of distribution and density seen in the adult. Electron microscopic analysis revealed that serotonin varicosities formed symmetrical or asymmetrical synapses mainly with dendritic shafts throughout postnatal life. Stereological extrapolation from single sections to the whole volume of varicosities showed that the percentage of serotonin varicosities engaged in synaptic junctions varied according to age. The proportion of labelled varicosities forming synapses increased from birth (21.3%) to the end of the second postnatal week (42.5%), then declined markedly in the following week (17.1%) before increasing again to an adult value of 46%. These findings suggest that the formation of synaptic connections by serotonin axons in the basal forebrain shows two distinct phases in postnatal development: exuberant synapses present in the first two weeks of life may be related to the involvement of serotonin in the maturation of this area, whereas synapses formed later in development may affect the functional state of basal forebrain projections to the neocortex and hippocampus. Thus, at these late stages of development and in the adult, serotonin may influence the activity of these forebrain structures both directly and indirectly.