Regional topography within noradrenergic locus coeruleus as revealed by retrograde transport of horseradish peroxidase

Abstract

A hitherto unsuspected degree of regional topographic organization in the noradrenergic nucleus, locus coeruleus, was revealed by the use of retrograde transport of horseradish peroxidase (HRP) from terminal areas receiving noradrenergic innervation. HRP was injected into hippocampus, hypothalamus, thalamus, caudate-putamen, septum, amygdala-piriform cortex, cerebellum and cortex. Successful transport was obtained from all areas, including the caudate-putamen and cerebral cortex. The pattern of HRP positive cells in the ipsilateral locus coeruleus was markedly different depending on the location of the HRP injection. Thus, hippocampal injections labeled cells in the dorsal locus coeruleus but not at all in the ventral tip. Injections of HRP into caudate-putamen or cerebellum labeled the ventral tip along with the rest of the dorsal portion. HRP injections into the septum labeled cells only in the dorsal half of the dorsal locus coeruleus. There thus exists a three tier division of locus coeruleus into the ventral one third, dorsal one third and intermediate one third. A further division was seen in the anterior-posterior plane with HRP injections into the thalamus labeling the posterior pole of locus very intensely but with little transport to more anterior levels; conversely HRP injection into the hypothalamus resulted in intense labeling only in the anterior pole of locus coeruleus. Amygdala-piriform cortex HRP injections revealed a further pattern with very intensely reactive cells scattered sparsely throughout the nucleus. Cortical HRP injections yielded weaker labeling also in occasional, scattered cells. All HRP transport to locus coeruleus was shown to be noradrenergic by degeneration with 6-hydroxydopamine and due to terminal, rather than fiber of passage, uptake by control injection into the dorsal NA bundle. It is concluded that the locus coeruleus is not an homogenous nucleus with respect to the origin of the noradrenergic projections to sundry forebrain, spinal and cerebellar areas but is comprised of distinct subdivisions of noradrenergic neurons.

Characterization of neurochemically specific projections from the locus coeruleus with respect to somatosensory‐related barrels

“…Noradrenergic fibers were described as highly ramified and localized in a sunburst orientation within the center of each barrel. Such organization is supported by other studies, which have shown selective connectivity between the rodent locus coeruleus (LC) and its efferent target sites (Mason and Fibiger, 1979;Cedarbaum and Saper, 1981;Waterhouse et al, 1983;Loughlin et al, 1986aLoughlin et al, , 1986bMorrison and Foote, 1986;Simpson et al, 1997). In general, these findings contradict other early investigations, which emphasized the diffuse projection pattern and global actions of the LC/norepinephrine (NE) system (Anden et al, 1966;Ungerstedt, 1971;Pickel et al, 1974;Nakamura and Iwama, 1975;AstonJones andBloom, 1981a, 1981b;Aston-Jones et al, 1986).…”

Histamine neuronal system as a therapeutic target for the treatment of cognitive disorders

“…In comparable architecture of noradrenergic, dopaminergic and serotonergic systems [117,118], somata of histaminergic neurons are restricted to discrete cell clusters in the hypothalamic TMN, and send their axons to innervate nearly the entire CNS [7,8]. Cathecolaminergic and serotonergic nuclei are comprised of distinct compartments with respect to projection fields, as distinct sets of axons innervating separate brain regions originate from separate subgroups of noradrenergic (A1-A7), dopaminergic (A8-A17) and serotonergic (B1-B9) neurons [117,118].…”

Direct and Indirect Inhibition by Catecholamines of Hypocretin/Orexin Neurons

“…But another possibility is that the NE axons that innervate the hypocretin neurons arise not primarily from the LC but from other NE neurons in the hindbrain, perhaps from A1 or A2, or other axons could arise from adrenergic neurons in C1 that project to the LH (Mason and Fibiger, 1979;). These cells have a different function from the LC neurons and may relate more to control of vegetative and homeostatic processes, potentially linking the enteroceptive cells of the gut with the LH.…”