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

doi:10.1016/0006-8993(92)90182-9

Brain Research

Volume 598, Issues 1–2, 11 December 1992, Pages 185-195

https://doi.org/10.1016/0006-8993(92)90182-9 Get rights and content

Abstract

The nucleus paragigantocellularis (PGi), located in the rostral ventrolateral medulla, is one of two major afferents to the nucleus locus coeruleus (LC). Electrical stimulation of PGi exerts a robust, predominantly excitatory influence on LC neurons that is blocked by intracerebroventricular (i.c.v.) administration of the broad spectrum excitatory amino acid (EAA) antagonists kynurenic acid (KYN) or γ-d-glutamylglycine (DGG), but not by the selective N-methyl-d-aspartate (NMDA) receptor antagonist 2-amino-7-phosphonoheptanoate (AP7). I.c.v. injection of KYN or DGG also blocked activation of LC neurons evoked by noxious somatosensory stimuli. These results indicate that activation of LC neurons by PGi and noxious stimuli may be mediated by an EAA acting at a non-NMDA receptor in LC. In the present study, microiontophoretic techniques were used to determine the sensitivity of LC neurons in vivo to the selective EAA receptor agonists kainate (KA), NMDA and quisqualate (QUIS). Microinfusion and microiontophoresis were also used to determine whether direct application of KYN, the preferential non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3 dione (CNQX) or the selective NMDA receptor antagonist 2-amino-5-phosphonovalerate (AP5) onto LC neurons blocked excitation elicited by stimulation of PGi or the sciatic nerve. The results demonstrated that individual LC neurons were robustly activated by direct application of KA, NMDA and QUIS. Iontophoretically applied KYN reduced or completely antagonized responses evoked by all 3 agonists. In contrast, iontophoretically applied AP5 strongly attenuated NMDA-evoked excitation, while KA-and QUIS-evoked responses were not affected by this agent. Furthermore, direct application of KYN or the specific non-NMDA receptor antagonist, CNQX, onto LC neurons substantially attenuated or completely blocked synaptic activation produced by PGi or sciatic nerve stimulation in nearly every LC neuron tested. Microinfusion of the selective NMDA receptor antagonist AP5 had no effect on sciatic nerve-evoked responses. These results confirm our hypothesis that activation of LC neurons from PGi is mediated by an EAA operating primarily at a non-NMDA receptor subtype on LC neurons. Furthermore, these findings provide additional support for the hypothesis that this pathway mediates at least some sensory-evoked responses of LC neurons.

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Citation Excerpt :
Previous studies demonstrated that noxious somatic stimulation in healthy animals activates LC neurons (heat, footshock, tail pinch, etc.: Cedarbaum and Aghajanian, 1978; Hirata and Aston-Jones, 1994; Hirata and Aston-Jones, 1996; Viisanen and Pertovaara, 2007; Llorca-Torralba et al., 2016) and consequently, there is an increase in noradrenaline release in terminal areas such as the spinal cord and prefrontal cortex among others (Korf et al., 1973; Florin-Lechner et al., 1996; Singewald and Philippu, 1998). This pattern of phasic discharge is characterized by a brief excitatory component followed by a refractory inhibitory period, and it is consistent with the glutamate release from the paragigantocellularis nucleus (PGi) that transmits nociceptive inputs from periphery (Ennis et al., 1992; Chiang and Aston-Jones, 1993). Previous data demonstrated that the response to noxious mechanical stimulation typically increases at the spinal cord level after nerve injury (Pertovaara et al., 1997), and we have previously shown that the PGi activity increases seven days after CCI (Alba-Delgado et al., 2012a).
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Activation of locus coeruleus neurons by nucleus paragigantocellularis or noxious sensory stimulation is mediated by intracoerulear excitatory amino acid neurotransmission

Abstract

Neurosci. Lett.

Neuroscience

Prog. Brain Res.

Neuropharmacology

Neurosci. Lett.

Brain Res.

Brain Res.

Brain Res.

Life Sci.

Neurosci. Lett.

Brain Res.

Brain Res.

Brain Res.

Brain Res.

Brain Res.

Neuroscience

Prog. Brain Res.

Exp. Neurol.

Neurosci. Lett.

Brain Res.

Brain Res.

Brain Res. Bull.

Neuroscience

Opiate withdrawal-induced hyperactivity of locus coeruleus neurons is substantially mediated by augmented excitatory amino acid input

J. Neurosci.

The nucleus paragigantocellularis lateralis in the rat. Demonstration of afferents by the retrograde transport of horseradish peroxidase

Anat. Embryol.

Electrophysiological evidence of adrenergic inhibition of locus coeruleus from the ventrolateral medulla

Soc. Neurosci. Abstr.

Behavioral functions of locus coeruleus derived from cellular attributes

Physiol. Psychol.

Serotonin selectively attenuatesglutamate-evoked activation of noradrenergic locus coeruleus neurons

J. Neurosci.

Lumbar cord innervates a specific subregion of the periaqueductal gray which projects to paragigantocellularis and prepositus hypoglossi, the major afferents to locus coeruleus (LC): possible connection between periphery and LC

Soc. Neurosci. Abstr.

Activity of norepinephrine-containing locus coeruleus neurons in behaving rats anticipates fluctuations in the sleep waking cycle

J. Neurosci.