Noradrenergic innervation of the developing and mature septal area of the rat.

The noradrenergic innervation of the developing and mature septal area of the rat was examined with light and electron microscopic immunocytochemistry using an antibody against dopamine-beta-hydroxylase. At birth, a small number of relatively thick noradrenergic fibers were found to innervate the lateral septum (mainly its intermediate part) and the nuclei of the vertical and horizontal limbs of the diagonal band of Broca. By postnatal day 7, a substantial increase in their density was observed. At this age some labeled fibers left the medial forebrain bundle and invaded the nucleus of the horizontal limb of the diagonal band. These fibers then ran in a ventrodorsal direction and innervated the nucleus of the vertical limb before entering the medial septum. Immunoreactive fibers were finer and more varicose than at birth. In the subsequent 2 weeks, the density of labeled fibers in the septal area was further increased. By postnatal day 21, the distribution pattern and density of the noradrenergic innervation appeared similar to the adult. In the adult, noradrenergic fibers exhibited more varicosities than in younger rats. Electron microscopic analysis revealed a low proportion (peaked at P7) of noradrenergic varicosities engaged in synaptic contacts throughout development. The overwhelming majority of these synapses were symmetrical, predominantly with small or medium-sized dendrites. The present findings provide the morphological basis for the functional interactions between noradrenergic afferents and neuronal elements in the septal area. The low proportion of synaptic contacts found in this study suggests that noradrenaline may exert its action in the septal area mainly through transmission by diffusion (volume transmission), as has been suggested for other areas of the developing and adult brain.

Postnatal development of the noradrenergic system in the dorsal lateral geniculate nucleus of the rat.

The noradrenergic innervation of the developing dorsal lateral geniculate nucleus of the rat was examined with light and electron microscopic immunocytochemistry. At birth, few, relatively thick, noradrenergic fibers innervated the nucleus. Their density was steadily increased and they became thinner, tortuous, and varicose with the progression of age. Only a minority (11-15%) of labeled varicosities made synaptic contacts. Most of these synapses were symmetrical and on dendritic shafts. The present findings demonstrate the establishment of the anatomical relationships between noradrenergic afferents and neurons of the dorsal lateral geniculate nucleus during development and may help to understand the role of noradrenaline in the processing of visual information.

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.