Differential development of the dual serotoninergic fiber system in the cerebral cortex of the cat

The changes in distribution and density of the serotoninergic innervation of the cerebral cortex were studied in kittens from birth (PO) to 60 days of age (P59). Three cortical areas were sampled: prefrontal, primary auditory, and primary visual areas. Two systems of serotoninergic axons were demonstrated by immunocytochemical techniques: the fine axon system characterized by small fusiform varicosities up to 1 micron in diameter, and the beaded axon system, the fibers of which have round varicosities up to 5 microns in diameter. The density of the two types of fibers across the cortical layers at different ages was measured with a semiautomatic computerized system. In all three areas, the density of fine axons increased steadily from birth, although the pattern of innervation changed from an even distribution at PO to a distinct concentration of the fibers in layers I-III by week 2 in the prefrontal cortex and by week 3 in auditory and visual cortices. By contrast, the beaded axons first appeared in the cortex at week 2 for the prefrontal cortex, at week 3 in auditory and visual areas. Initially, these fibers were distributed throughout all cortical layers and were of much lower density than the fine axons. At later ages the beaded axons became confined to layers I-III where they gradually increased in number, and from week 4, they formed pericellular arrays which were only observed in the prefrontal and auditory cortices, not in visual cortex. These findings provide further evidence for the existence of two parallel subsystems of serotoninergic axons which are different not only in their morphology and nuclear origin, but also in their development. Our finding that the two serotoninergic fiber systems arrive in the cortex in two different stages suggests that they have differential roles in development. The late formation of the pericellular arrays indicates that the formation of the specific connections made by the beaded fibers could be dependent on a certain degree of maturity of the target neurons.