Article
Cotransmitter-mediated locus coeruleus action on motoneurons

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Abstract

This article reviews evidence for a direct noradrenergic projection from the dorsolateral pontine tegmentum (DLPT) to spinal motoneurons. The existence of this direct pathway was first inferred by the observation that antidromically evoked responses occur in single cells in the locus coeruleus (LC), a region within the DLPT, following electrical stimulation of the ventral horn of the lumbar spinal cord of the cat. We subsequently confirmed that there is a direct noradrenergic pathway from the LC and adjacent regions of the DLPT to the lumbar ventral horn using anatomical studies that combined retrograde tracing with immunohistochemical identification of neurotransmitters. These anatomical studies further revealed that many of the noradrenergic neurons in the LC and adjacent regions of the DLPT of the cat that send projections to the spinal cord ventral horn also contain colocalized glutamate (Glu) or enkephalin (ENK). Recent studies from our laboratory suggest that Glu and ENK may function as cotransmitters with norepinephrine (NE) in the descending pathway from the DLPT. Electrical stimulation of the LC evokes a depolarizing response in spinal motoneurons that is only partially blocked by α1 adrenergic antagonists. In addition, NE mimicks only the slowly developing and not the fast component of LC-evoked depolarization. Furthermore, the depolarization evoked by LC stimulation is accompanied by a decrease in membrane resistance, whereas that evoked by NE is accompanied by an increased resistance. That Glu may be a second neurotransmitter involved in LC excitation of motoneurons is supported by our observation that the excitatory response evoked in spinal cord ventral roots by electrical stimulation of the LC is attenuated by a non-N-methyl-d-aspartate glutamatergic antagonist. ENK may participate as a cotransmitter with NE to mediate LC effects on lumbar monosynaptic reflex (MSR) amplitude. Electrical stimulation of the LC has a biphasic effect on MSR amplitude, facilitation followed by inhibition. Adrenergic antagonists block only the facilitatory effect of LC stimulation on MSR amplitude, whereas the ENK antagonist naloxone reverses the inhibition. The chemical heterogeneity of the cat DLPT system and the differential responses of motoneurons to the individual cotransmitters help to explain the diversity of postsynaptic potentials that occur following LC stimuli.

References (89)

  • S.J. Fung et al.

    Locus coeruleus control of spinal cord activity. Brainstem control of spinal cord function

  • S.J. Fung et al.

    Membrane excitability changes in hind-limb motoneurons induced by stimulation of the locus coeruleus in cats

    Brain Res.

    (1987)
  • S.J. Fung et al.

    Locus coeruleus control of spinal motor output

    Prog. Brain Res.

    (1991)
  • S.J. Fung et al.

    Coerulospinal cells containing neuropeptide Y in the cat

    Peptides

    (1991)
  • T. Furuyama et al.

    Region-specific expression of subunits of iontropic glutamate receptors (AMPA-type, KA-type and NMDA receptors) in the rat spinal cord with specific reference to nociception

    Mol. Brain Res.

    (1993)
  • H.S. Goldsmith et al.

    Axonal regeneration after spinal cord transection and reconstruction

    Brain Res.

    (1992)
  • C. Gouarderes et al.

    High resolution radioautographic localization of [125I]FK-33–824-labelled mu opioid receptors in the spinal cord of normal and deafferented rats

    Neuroscience

    (1991)
  • P.G. Guyenet

    The coeruleospinal noradrenergic neurons: Anatomical and electrophysiological studies in the rat

    Brain Res.

    (1980)
  • M.B. Hancock et al.

    Spinal projections from the nucleus locus coeruleus and nucleus subcoeruleus in the cat and monkey as demonstrated by the retrograde transport of horseradish peroxidase

    Brain Res. Bull.

    (1976)
  • G. Holstege et al.

    Anatomical evidence for direct brain stem projection to the somatic motoneuronal cell groups and autonomic preganglionic cell groups in cat spinal cord

    Brain Res.

    (1979)
  • J.R. Howe et al.

    Characterization of [3H]rauwolscine binding to alpha2-adrenoceptor sites in the lumbar spinal cord of the cat: Comparison to such binding sites in the cat frontal cerebral cortex

    Brain Res.

    (1986)
  • T. Kaneko et al.

    Immunohisto-chemical demonstration of glutaminase in catecholaminergic and serotoninergic neurons of rat brain

    Brain Res.

    (1990)
  • H.G.J.M. Kuypers et al.

    Funicular trajectories of descending brain stem pathways in cat

    Brain Res.

    (1977)
  • Y.-Y. Lai et al.

    A spinal projection of serotonergic neurons of the locus coeruleus in the cat

    Neurosci. Lett.

    (1985)
  • Y.-Y. Lai et al.

    The actions of two monoamines on spinal motoneurons from stimulation of the locus coeruleus in the cat

    Brain Res.

    (1989)
  • J. Lechner et al.

    Brainstem peptidergic neurons projecting to the medial and lateral thalamus and zona incerta in the rat

    Brain Res.

    (1993)
  • L. Leger et al.

    Localization of substance P- and enkephalin-like immunoreactivity in relation to catecholamine-containing cell bodies in the cat dorsolateral pontine tegmentum: An immunofluorescence study

    Neuroscience

    (1983)
  • J.L. Maderdrut et al.

    Distribution and development of proenkephalin-like immunoreactivity in the lumbar spinal cord of the chicken

    Brain Res.

    (1986)
  • S.A. Marks et al.

    [3H]Prazosin binding in the intermediolateral cell column and the effects of iontophoresed methoxamine on sympathetic preganglionic neuronal activity in the anaesthetized cat and rat

    Brain Res.

    (1990)
  • M.L. Mayer et al.

    The physiology of excitatory amino acids in the vertebrate central nervous system

    Prog. Neurobiol.

    (1987)
  • L.F. McNicholas et al.

    Innervation of the spinal cord by sympathetic fibers

    Exp. Neurol.

    (1980)
  • S. Miachon et al.

    Identification of catecholamine cell bodies in the pons and ponsmesencephalon junction of the cat brain, using tyrosine hydroxylase and dopamine-β-hydroxylase immunohistochemistry

    Brain Res.

    (1984)
  • J.J. Mitchell et al.

    Quantitative autoradiographic analysis of excitatory amino acid receptors in the cat spinal cord

    Neurosci. Lett.

    (1991)
  • P.J. Monroe et al.

    Evaluation of the interactions of serotonergic and adrenergic drugs with μ, δ, and κ opioid binding sites

    Neurosci. Lett.

    (1991)
  • P. Mouchet et al.

    Immunohistochemical study of catecholaminergic cell bodies in the rat spinal cord

    Brain Res. Bull.

    (1986)
  • P. Mouchet et al.

    Immunohistochemical study of the catecholaminergic innervation of the spinal cord of the rat using specific antibodies against dopamine and noradrenaline

    J. Chem. Neuroanat.

    (1992)
  • T. Nakazato

    Locus coeruleus neurons projecting to the forebrain and the spinal cord in the cat

    Neuroscience

    (1987)
  • A.P. Nicholas et al.

    Serotonin-, substance P- and glutamate/aspartate-like immunoreactivities in medullo-spinal pathways of rat and primate

    Neuroscience

    (1992)
  • L.G. Nygren et al.

    A new major projection from locus coeruleus: The main source of noradrenergic nerve terminals in the ventral and dorsal columns of the spinal cord

    Brain Res.

    (1977)
  • O. Pompeiano et al.

    Responses of locus coeruleus and subcoeruleus neurons to sinusoidal stimulation of labyrinth receptors

    Neuroscience

    (1990)
  • V.K. Reddy et al.

    Pontospinal transmitters and their distribution

    Prog. Brain Res.

    (1991)
  • B. Scatton et al.

    Degeneration of noradrenergic and serotonergic but not dopaminergic neurones in the lumbarspinal cord of parkinsonian patients

    Brain Res.

    (1986)
  • B. Skoog et al.

    Do noradrenergic descending tract fibres contribute to the depression of transmission from group II muscle afferents following brainstem stimulationin the cat?

    Neurosci. Lett.

    (1991)
  • K.A. Sluka et al.

    Spinal projections of the locus coeruleus and the nucleus subcoeruleus in the Harlan and the Sasco Sprague-Dawley rat

    Brain Res.

    (1992)
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    2

    Present address: Veterans General Hosp., VACRS, Taipei, Taiwan 112, Republic of China.

    3

    Present address: Dept. Fisiol. e Biochim., Univ. di Pisa, Via S Zeno 31, 56100 Pisa, Italy.

    4

    Present address: Dept. Psychiat., Neurobiol. Res., 151A3, VA Med. Ctr., Sepulveda, CA 91343.

    5

    Present address: Dept. Neurosci., Texas Tech. Univ. Hlth. Sci. Ctr., Lubbock, TX 79430.

    6

    Present address: Dept. Pharmacol., Uniformed Services Univ. Hlth. Sci., Bethesda, MD 20814.

    7

    Present address: Dept. Physiol., UCLA, Los Angeles, CA 90024.

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