Elsevier

Neuroscience

Volume 53, Issue 3, April 1993, Pages 705-715
Neuroscience

Response of locus coeruleus neurons to footshock stimulation is mediated by neurons in the rostral ventral medulla

https://doi.org/10.1016/0306-4522(93)90618-PGet rights and content

Abstract

While it is well documented that locus coeruleus neurons are potently activated by footpinch or sciatic nerve stimulation, little is known about the circuit producing this sensory response. Previous work in our laboratory has identified the medullary nucleus paragigantocellularis as a major excitatory afferent to the locus coeruleus. Here, we use local microinjections into the paragigantocellularis to test whether this nucleus is a link in the pathway mediating the activation of locus coeruleus neurons by subcutaneous footpad stimulation, or footshock, in anesthetized rats. Lidocaine HCl microinjected into the paragigantocellularis reversibly attenuated footshock-evoked activation of 50 out of 56 locus coeruleus cells, with responses in 20 cells completely blocked. Microinjections of GABA into the paragigantocellularis reduced the footshock-evoked responses of 17 out of 27 locus coeruleus cells (seven complete blocks); microinjections of the GABAB agonist baclofen had no effect (0 out of 11 cells blocked). Microinjections of a synaptic decoupling cocktail of manganese and cadmium also attenuated locus coeruleus activation in eight out of nine cells with two complete blocks. With each agent, the most effective injection placement for complete blockade of responses was the ventromedial paragigantocellularis; injections bordering this region attenuated responses, while those outside of the paragigantocellularis (dorsal medullary reticular formation, nucleus tractus solitarius, or facial nucleus), or vehicle injections, were ineffective.

These results are consistent with previous findings that pharmacologie blockade of paragigantocellularis-evoked locus coeruleus activity also blocks footshock-evoked responses of locus coeruleus neurons [Ennis and Aston-Jones (1988) J. Neurosci.8, 3644–3657], and support the view that this somatosensory response, and perhaps other sensory-evoked responses of locus coeruleus neurons, involve the nucleus paragigantocellularis.

Reference (70)

  • DampneyR.A.L. et al.

    Role of ventrolateral medulla in vasomotor regulation: a correlative anatomical and physiological study

    Brain Res.

    (1982)
  • ElamM. et al.

    Locus coeruleus neurons and sympathetic nerves: activation by cutaneous sensory afferents

    Brain Res.

    (1986)
  • ElamM. et al.

    Locus coeruleus neurons and sympathetic nerves: activation by visceral afferents

    Brain Res.

    (1986)
  • ElamM. et al.

    Hypercapnia and hypoxia: chemoreceptor-mediated control of locus coeruleus neurons and splanchnic, sympathetic nerves

    Brain Res.

    (1981)
  • EngbergG.

    Nicotine induced excitation of locus coeruleus neurons is mediated via release of excitatory amino acids

    Life Sci.

    (1989)
  • EnnisM. et al.

    A potent excitatory input to the nucleus locus coeruleus from the ventrolateral medulla

    Neurosci. Lett.

    (1986)
  • EnnisM. et al.

    Two physiologically distinct populations of neurons in the ventrolateral medulla innervate the locus coeruleus

    Brain Res.

    (1987)
  • EnnisM.E. et al.

    Activation of locus coeruleus neurons by nucleus paragigantocellularis or noxious sensory stimulation is mediated by intracoerulear excitatory amino acid neurotransmission

    Brain Res.

    (1992)
  • GuyenetP.G.

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

    Brain Res.

    (1980)
  • GuyenetP.G. et al.

    Comparative effects of sciatic nerve stimulation, blood pressure, and morphine on the activity of A5 and A6 pontine noradrenergic neurons

    Brain Res.

    (1985)
  • HajosM. et al.

    A role of excitatory amino acids in the activation of locus coeruleus neurons following cutaneous thermal stimuli

    Brain Res.

    (1990)
  • KeelerJ.R. et al.

    The ventral surface of the medulla in the rat: pharmacologic and autoradiographic localization of GABA-induced cardiovascular effects

    Brain Res.

    (1984)
  • KimuraF. et al.

    Locus coeruleus neurons in the neonatal rat: electrical activity and responses to sensory stimulation

    Devl Brain Res.

    (1985)
  • KorfJ. et al.

    Noradrenergic neurons: morphine inhibition of spontaneous activity

    Eur. J. Pharmac.

    (1974)
  • KuanY.F. et al.

    Ca-channel blockers and the electrophysiology of synaptic transmission of the guinea-pig olfactory cortex

    Eur. J. Pharmac.

    (1986)
  • LovickT.A.

    Projections from brainstem nuclei to the nucleus paragigantocellularis lateralis in the cat

    J. auton. nerv. Syst.

    (1986)
  • MalpeliJ.G. et al.

    A method of reversible inactivation of small regions of brain tissue

    J. Neurosci. Meth.

    (1979)
  • McAllenR.M. et al.

    Effects of kainic acid applied to the ventral surface of the medulla oblongata on vasomotor tone, the baroreceptor reflex and hypothalamic autonomic responses

    Brain Res.

    (1982)
  • McMahonS.B. et al.

    Electrophysiological mapping of brainstem projections of spinal cord lamina I cells in the rat

    Brain Res.

    (1985)
  • PieriboneV.A. et al.

    Adrenergic innervation of the rat nucleus locus coeruleus arises predominantly from the C1 adrenergic cell group in the rostral medulla

    Neuroscience

    (1991)
  • ShiekhattarR. et al.

    Local infusion of calcium-free solutions in vivo activates locus coeruleus neurons

    Brain Res. Bull.

    (1991)
  • SvenssonT.H. et al.

    Brain noradrenergic neurons in the locus coeruleus: inhibition by blood volume load through vagal afferents

    Brain Res.

    (1979)
  • ValentinoR.J. et al.

    Activation of noradrenergic locus coeruleus neurons by hemodynamic stress is due to local release of corticotropin-releasing factor

    Brain Res.

    (1991)
  • AkaokaH. et al.

    Electrophysiological effects of local administration of apomorphine in the rat substantia nigra zona compacta

    Neuroscience

    (1987)
  • AndrezikJ.A. et al.

    The nucleus paragigantocellularis lateralis in the rat. Conformation and cytology

    Anat. Embryol.

    (1981)
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