The central adrenergic system. An immunofluorescence study of the location of cell bodies and their efferent connections in the rat utilizing dopamine‐B‐hydroxylase as a marker

Abstract

A sensitive immunofluorescence technique was used to describe systematically the distrubution of dopamine-beta-hydroxylase (DBH)-containing cell bodies, non-terminal fiber pathways, and terminal fields in the brain of the male albino rat. DBH is the enzyme that catalyzes the conversion of dopamine to noradrenaline, and as such is useful as an anatomical marker for noradrenaline and possibly adrenaline neurons. The enzyme is not present in dopamine- or indolamine-containing neurons. Ten micron frozen sections (1-in 20 series) were prepared in the frontal, sagittal, and horizontal planes from the olfactory bulb to the upper cervical segments of the spinal cord; adjacent sections in each plane were stained for DBH and for cells (toluidine blue=azure II). An atlas consisting of 40 projection drawings of selected frontal sections illustrates the results of the investigation. DBH perikarya are confined to three groups in the pons and medulla: the well defined locus coeruleus, a more diffuse but continuous subcoeruleus group that arches through the pons and ventral medulla, and a third dorsal medullary group centered in the dorsal motor nucleus of the vagus. A single principal adrenergic fiber system distributes a great many of the axons from these neuron groups to a majority of nuclear areas in the brain. In the pons and medulla two components of the fiber system may be distinguished. A medullary branch may be followed from the posterior aspect of the subcoeruleus group dorsally and then anteriorly through the lateral tegmental field and ventral aspect of the vestibular complex to a position subjacent to the locus coeruleus, where it is joined by a subcoeruleus branch consisting of a large number of fibers coursing among cells along the length of the subcoeruleus group, and by fibers arising from the locus coeruleus. Anterior to the locus coeruleus the principal adrenergic bundle courses as a single fiber tract immediately ventrolateral to the central gray in the mesencephalon and in the zona incerta and substantia innominata in the diencephalon. At the level of the septal area separate bundles reach the cortex dorsally over the genu of the corpus calosum via the medial septal-diagonal band nuclei and the lateral septum and ventrally between the olfactory tubercle and caudate-putamen. In the medulla and pons adrenergic fibers undoubtedly course in both directions. Anterior to the most rostral pontine cell bodies, however, all fibers presumably ascend. Along the course of the bundle distinct branches emerge to innervate circumscribed terminal fields. In addition, certain regions of the brain such as the reticular formation and pontine gray receive diffuse DBH innervation derived from less clearly defined pathways. A small number of areas in the brain contain little or no detectable DBH. These include the caudate-putamen, nucleus accumbens, globus pallidus, olfactory tubercle, subthalamic nucleus, substantia nigra, pretectal area, third, fourth and sixth cranial verve nuclei, and the trapezoid body nucleus.

There and Back Again: A Tale of Norepinephrine and Drug Addiction

“…Conversely, lesions of the LC decrease striatal DA neuron activity (Tassin et al, 1979) and DA release (Russell et al, 1989;Lategan et al, 1990;Lategan et al, 1992). The PFC, a brain region implicated in responses to psychostimulants, also receives dense noradrenergic input from the LC (Swanson and Hartman, 1975;Morrison et al, 1981), which then sends excitatory glutamatergic projections to dopaminergic VTA neuronsFthough this connection may involve another glutamatergic relay nucleus (Carr and Sesack, 2000). Finally, the VNB projects directly to the NAc (Berridge et al, 1997;Delfs et al, 1998;Tong et al, 2006).…”

“…Currently, activation of an AR by DA in vivo is supported by good evidence in just one instance: a2cARs in the striatum. Given the relatively sparse noradrenergic innervation of the striatum (Lindvall and Björklund, 1974;Swanson and Hartman, 1975), there is a surprising abundance of a2ARs in this region, especially the a2cAR (Ordway et al, 1993;Nicholas et al, 1993;Uhlen et al, 1997). This paradox led Ordway et al to propose that DA, rather than NE, is the endogenous ligand for a2cARs in the striatum (Zhang et al, 1999).…”

Electrophysiological properties of catecholaminergic neurons in the norepinephrine-deficient mouse

“…In addition, the LC projects directly to, and modulates the activity of, midbrain dopamine (DA) neurons (Swanson and Hartman, 1975;Jones and Moore, 1977;Liprando et al, 2004), which are critical for reward and motor related behaviors (Girault and Greengard, 2004;Montague et al, 2004). In an intact animal, NE neurons recorded in vitro fire spontaneously in a single-spike Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication.…”

“…Additionally, bath application of dopamine at high concentrations only modestly induces an outward current in both control and Dbh −/−mice, and this effect may be mediated by D2-like receptors (Yokoyama et al, 1994;Suzuki et al, 1998). The LC and other NE nuclei (A1/A2 NE cell region) project directly to, and modulate the activity of, midbrain DA neurons (Swanson and Hartman, 1975;Jones and Moore, 1977;Liprando et al, 2004), and both basal and amphetamine-induced striatal DA release is compromised in Dbh −/− mice (Schank et al, 2005). Therefore, the sensitivity of DA neurons to exogenous application of DA was also tested.…”

6-Hydroxydopamine lesion of the rat prefrontal cortex impairs motor initiation but not motor execution

“…Furthermore, the PFC receives a dopaminergic innervation from mesocortical dopamine (DA) cells (Bj6rklund and Lindvall 1984) and DAergic axon terminals exhibit synaptic contacts mainly with pyramidal neurons in deeper cortical layers (Verney et al 1990). Besides, there exists a noradrenergic innervation which originates in the locus coeruleus and projects particularly to the superficial cortical layers (Swanson and Hartman 1975).…”