Locus Coeruleus

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This chapter discusses neurochemical properties of locus coeruleus (LC) neurons and the neurotransmitters that are found in neuronal inputs to and outputs from the locus coeruleus. The LC is a dense group of cells in the lateral part of the pontine tegmentum. The axons of LC neurons give off fine collaterals within the nucleus that terminate on dendrites there. The most characteristic ultrastructural feature of LC cells is their high number of somatic and dendritic spines. Almost half of the norepinephrine cells in the central nervous system reside in the LC. Moderately high serotonin levels and tryptophan hydroxylase activity have been measured in rat LC. Cells in the LC may participate in controlling cortical blood flow, systemic blood pressure, respiratory patterns, micturation, arousal, sleep, food and water intake, and release of anterior pituitary hormones. The physiological, pharmacological, and anatomical studies that have been performed to date point toward a special integrative role for LC neurons.

Introduction

The locus coeruleus, a small group of relatively uniform neurons in the pontine tegmentum, has been recognized for more than 170 years (ref. Russell, 1955). In the century following its discovery, the topography of the locus coeruleus was studied in detail and its role in the central nervous system was discussed at length, to little avail. Ramón y Cajál (1909) was the first—as he was so often—to give a correct description of the neuronal structure and fiber network of the locus coeruleus.

The physiological role of the locus coeruleus remained a mystery until about 25 years ago. Without any definitive knowledge of the physiological properties of the locus coeruleus, Russell (1955) concluded that “certainly it would not be unexpected if several, or all, vegetative phenomena received some suprasegmental facilitatory or suppressor influences through a relay center such as the locus coeruleus.” Five years later, based on rather nonspecific histochemical techniques, Maeda et al. (1960) suggested that aromatic monoamines such as catecholamines and serotonin might be concentrated in the locus coeruleus. A few years later, cells in the locus coeruleus were indeed shown to contain norepinephrine and to send processes to a variety of central structures (Dahlström and Fuxe, 1964). Since that time hundreds of publications describing the locus coeruleus have appeared in the literature. Many of these papers have stressed the role of locus coeruleus neurons in regulating autonomic and vegetative functions.

Our article will not provide detailed summaries of data on the function or morphology of the locus coeruleus. A lengthly review of these fields was published a few years ago (Amaral and Sinnamon, 1977). Furthermore, excellent and extensive reviews of its anatomy (Swanson, 1976a), phylogeny (Russell, 1955), neuronal connections (Moore and Bloom, 1979; Levitt and Moore, 1979), and physiology (Amaral and Sinnamon, 1977; Moore and Bloom, 1979) have appeared. We shall focus, in this article, on the neurochemical properties of locus coeruleus neurons and the neurotransmitters which are found in neuronal inputs to and outputs from the locus coeruleus.

Section snippets

Topography

The locus coeruleus (LC) is a dense group of cells in the lateral part of the pontine tegmentum. These cells extend from the level of the rostral tip of the fourth ventricle (or the caudal end of the aqueduct), rostrally, to the internal genu of the facial nerve, caudally. In terms of its volume and the number of cells that it contains, the LC is a small nucleus, comprised of only 1400–1600 cells in rats (Descarries and Saucier, 1972; Swanson, 1976a). Since it is a small, dense collection of

Biochemistry and Immunocytochemistry

Ever since the demonstration by Dahlström and Fuxe (1964) that the LC is composed almost entirely of norepinephrine-containing neurons, the LC has been considered to be the major noradrenergic nucleus in the brain. This has obscured, until recently, the fact that there are cells in the LC which synthesize neurotransmitter substances besides norepinephrine. In some of these cells the other transmitter coexists with norepinephrine; in others it does not. These statements are based on both

Efferents from the Locus Coeruleus

Various neuroanatomical techniques have been used to study efferent (projecting) pathways and terminal fields of LC neurons. Some of these, such as anterograde (Pickel et al., 1974; Jones et al., 1977; Jones and Moore, 1977; Hopkins and Holstege, 1978) or retrograde (Mason and Fibiger, 1979) tracing techniques have proved very useful in demonstrating projections in detail; others, such as electron microscopy, have aided in the visualization of terminal fields (Záborszky et al., 1977). Two new

Afferents to the Locus Coeruleus

Part of the nerve terminals in the LC are intrinsic, i.e., they are terminals of recurrent axons. The number of intrinsic vs extrinsic nerve endings has not been determined, and all the sources of the extrinsic nerve endings have not been elucidated yet. In spite of this, cells in many brain areas—the spinal cord, medulla oblongata, mesencephalon, hypothalamus, thalamus, amygdala, and cerbral cortex—are thought to project to the LC. Some of the cells that innervate the LC have been chemically

Pharmacology of the Locus Coeruleus Neurons

Many putative neurotransmitters have been discovered in nerve terminals in the locus coeruleus (see Tables I and II), but their actions on LC neurons are as yet incompletely understood.

  • 1.

    Norepinephrine. Aghajanian and his colleagues (1977) have shown that norepinephrine, epinephrine, and isoproterenol depress LC unit activity, while administration of the α-adrenergic receptor antagonist, piperoxane, produces an increase in the activity of LC cells. Based on these findings, they have

Physiology

Cells in the locus coeruleus may participate in controlling cortical blood flow (Katayama et al., 1981), systemic blood pressure (Snyder and Reis, 1975), respiratory patterns (Johnson and Russell, 1952), micturation (Kuru, 1965), arousal (Moore and Bloom, 1979), sleep (Jouvet and Delorme, 1967), food and water intake (Osumi et al., 1975), and release of anterior pituitary hormones (Sawyer, 1975; Ganong, 1974).

The data that support these claims are typically somewhat indirect. The methods for

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