Density Of Noradrenergic Fibers Research Articles

The noradrenergic innervation of the vasa nervorum in old rats: a fluorescence histochemical study

The effect of ageing on the density and pattern of noradrenergic nerves in the perivascular nerve plexus supplying the vasa nervorum of the rat sciatic nerve was studied using combined catecholamine histofluorescence and quantitative image analysis techniques. The density of noradrenergic fibres around arteries and arterioles of the rat sciatic nerve vasa nervorum increased in the old animals. In contrast, no changes in perivascular nerve fibres supplying the veins and venules were found in the vasa nervorum of old rats. The increase in old age of noradrenergic innervation of arteries and arterioles of the vasa nervorum may be related to the pathogenesis of some peripheral nerve diseases.

Changes in the noradrenergic innervation of the area dentata after axotomy of coeruleohippocampal projections or unilateral lesion of the locus coeruleus

Lesions of the septal region result in a significant decrease in the norepinephrine content of the area dentata. Over a period of one year, norepinephrine levels return to normal, presumably due to the proliferation of remaining locus coeruleus fibers. Unilateral lesions of the locus coeruleus produce reductions in [3H]norepinephrine uptake values of about 70% and 30% in the ipsilateral and contralateral area dentata, respectively. By 12 weeks after lesion, the noradrenergic fiber density in the contralateral area dentata is within the range of control measurements, whereas the area dentata ipsilateral to the lesion remains significantly depleted of noradrenergic fibers. At 26 weeks postlesion, no further change was observed in the noradrenergic fiber density of either area dentata. These results are interpreted in light of the hypothesis that locus coeruleus axon proliferation is induced by axotomy and represents the expansion of intact collaterals of damaged fibers.

Alterations of the cortical noradrenergic system in chronic cobalt epileptogenic foci in the rat: A histofluorescent and biochemical study

Various models of acute experimentally-induced epilepsy indicate that aminergic neurons are involved. It has been demonstrated that a decrease in the level of norepinephrine can increase the susceptibility to epileptic seizures. The present research was undertaken in order to study alterations in the cortical noradrenergic system during the evolution of a chronic epileptic model induced by application of metallic cobalt on the sensorimotor cortex in the rat. The alterations were studied by means of the glyoxylic histochemical fluorescence method combined with biochemical analysis of cortical norepinephrine content. This histochemical and biochemical approach revealed a decrease in the density of noradrenergic terminals in the perifocal area. This decrease corresponds to a significant drop in the norepinephrine level, before the onset of spiking activity. Noradrenergic fiber density was still low and the norepinephrine level was lowest when the first epileptic discharges were recorded. At the end of the epileptic syndrome, sprouting of noradrenergic fibers into the perifocal area coincided with an increase in the norepinephrine level. Thus, this study gives further support to the hypothesis that noradrenergic system is involved in epileptogenesis.

The intra-cortical trajectory of the coeruleo-cortical projection in the rat: A tangentially organized cortical afferent

Cortical and sub-cortical lesions in the rat were used to analyze the intracortical trajectory of the noradrenergic axons, which were visualized by aldehyde-induced catecholamine histofluorescence and by immunohistochemistry using an antibody directed against rat dopamine-β-hydroxylase. Following subcortical lesions there is a slowly progressive reduction in the density of cortical noradrenergic axons, indicating that they undergo asynchronous anterograde degeneration. By 2 weeks after transection of the dorsal noradrenergic bundle, no dopamine β-hydroxylase-immunoreactive fibers are detectable in the ipsilateral cortex. Neither transection of the cingulum bundle, nor parasagittal incisions through the dorsal cortex lateral to the cingulum, diminished the noradrenergic innervation of medial or dorso-lateral cortex. A cortical lesion medial to the cingulum bundle markedly reduced the density of noradrenergic fibers in cingulate cortex caudal to the lesion, but did not affect the innervation of dorso-lateral cortex. In contrast, dorso-lateral frontal incisions and decortication (frontal lobotomy) produced a marked ipsilateral decrease in the noradrenergic fiber density throughout the remaining dorso-lateral cortex, while sparing the innervation of cingulate and infra-rhinal cortex. These results demonstrate that the dorso-lateral cortex is innervated by noradrenergic fibers in the medial forebrain bundle that reach the frontal pole, turn dorsally over the anterior portion of the forceps minor and continue caudally within the deep layers of frontal and dorso-lateral cortex, supplying the noradrenergic innervation throughout their trajectory. The medial cortex is innervated by a separate group of noradrenergic fibers that ascend through the septum, curve over the genu of the corpus callosum, and run caudally in the supracallosal stria. The present results show that the cingulum bundle is not a major intra-cortical noradrenergic pathway and does not provide branches that contribute significantly to the innervation of dorsal or lateral cortex. Thus the medial and lateral cortex can be selectively and differentially denervated of noradrenergic fibers and a coarse topographic order exists in the noradrenergic innervation of cortex. Since noradrenergic fibers travel long distances within the cortical grey matter, a small lesion of frontal cortex can have far-reaching effects on the innervation of distant, more caudal regions of cortex. The coeruleocortical projection has properties that differ from those of the best characterized cortical afferents and may be a useful model for the study of other ascending monoamine systems. The tangential, intracortical trajectory of the noradrenergic fibers would confer upon the coeruleo-cortical system the capacity to modulate neuronal activity simultaneously through a vast expanse of neocortex. A formulation of cortical organization is presented which integrates the tangential organization of the coeruleo-cortical projection with the concept of columnar organization of cortex.

Noradrenergic innervation patterns in three regions of medial cortex: An immunofluorescence characterization

A homologous antiserum directed against rat dopamine β-hydroxylase (DBH) was used for the immunohistofluorescent visualization of the noradrenergic (NA) innervation of medial cortex in the albino rat. Three cytoarchitectonic divisions of the medial cortex were studied: prelimbic (PL), anterior cingulate (AC), and granular retrosplenial (RSg). Each division of medial cortex possesses a characteristic and distinct pattern and density of NA fibers. The branching patterns and density of the fibers in PL cortex are similar to those of lateral cortex. AC cortex has the lowest density of NA innervation found in the neocortex; there is minimal arborization in layer I, and a very low density of fibers in layers II and III. In contrast RSg is the most densely innervated region, and NA fibers arborize extensively throughout all layers. The dopaminergic (DA) fibers in medial cortex were studied with glyoxylic acid-induced histofluorescence following midbrain lesions of the dorsal noradrenergic bundle (DNB). A laminar complementarity exists in AC cortex such that the DA fibers terminate in layers I–III, while the NA fibers are largely confined to the deep layers. The distinctive patterns of termination of coeruleocortical fibers indicate that in different cortical areas NA axons contact different elements of neuronal circuitry and that there is some degree of specificity in the distribution of NA terminals within the cortex.

Intracranial self-stimulation in relation to the ascending noradrenergic fiber systems of the pontine tegmentum and caudal midbrain: A moveable electrode mapping study

Chronically implanted moveable electrodes were used to map the pontine tegmentum and caudal midbrain for intracranial self-stimulation in relation to the ascending noradrenergic systems as revealed by fluorescence histochemistry. In no area tested was there a consistent correlation between the quality or the presence of self-stimulation and the degree of noradrenergic fiber density or cellular aggregation. Of particular importance was the failure to obtain self-stimulation from the locus coeruleus, despite repeated testing and extensive attempts at behavioral shaping. Those areas supporting self-stimulation included the dorsal raphe nucleus, the superior cerebellar peduncle and the mesencephalic and motor nuclei of the trigeminal nerve. These data appear to rule out activation of the ascending noradrenergic systems as an explanation of the rewarding effects of stimulation in these areas. A gustatory-visceral fiber system is suggested as an alternative possible substrate.