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

Matthew Ennis, Gary Aston-Jones, Ramin Shiekhattar

Research output: Contribution to journalArticlepeer-review

115 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)185-195
Number of pages11
JournalBrain research
Issue number1-2
StatePublished - Dec 11 1992
Externally publishedYes


  • 2-Amino-5-phosphonovalerate
  • CNQX
  • Glutamate
  • Kynurenate
  • Noradrenaline
  • Sensory response
  • Ventrolateral medulla

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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