Noradrenergic innervation of the developing and mature visual and motor cortex of the rat brain: a light and electron microscopic immunocytochemical analysis.

The noradrenergic (NA) innervation of the developing and adult visual and motor cortex of the rat was examined with light and electron microscopic immunocytochemistry by using antibodies against dopamine-beta-hydroxylase. At birth, NA fibers were present in both cortical areas, appearing as two tangential streams, one above and the other below the cortical plate. During the subsequent weeks, these two streams arborized gradually innervating all cortical layers. The adult pattern of distribution was attained by postnatal day 14, but the density of innervation, which was higher in the motor than in the visual cortex, appeared similar to the adult by the end of the third postnatal week. Electron microscopic analysis revealed that a low proportion of NA varicosities (the highest value was 12% in the adult motor cortex in single sections) were engaged in synaptic contact, throughout development, in both areas examined. The overwhelming majority of these synapses were symmetrical, involving predominantly small or medium dendrites. This evidence suggests that transmission by diffusion is the major mode of NA action in the developing and adult cerebral cortex. Noradrenaline released in the rare synaptic junctions may act mainly to reduce the activity of its cortical targets. The results altogether provide morphologic evidence for an involvement of noradrenaline in the development of the neocortex and, along with earlier data on the serotonergic system, indicate that the monoaminergic systems are endowed with a specific anatomic organization in various areas of the brain. Copyright 2002 Wiley-Liss, Inc.