NMDA-receptor-mediated sensory responses of brain noradrenergic neurons are suppressed by in vivo concentrations of extracellular magnesium.
Recent studies reveal at least three receptor subtypes for excitatory amino acid (EAA) neurotransmitters. Activation of one of these, the N-methyl-D-aspartate (NMDA) receptor-channel complex, has been strongly implicated in neuronal mechanisms of several important brain processes, including learning and memory. As NMDA receptors are highly sensitive to extracellular magnesium (Mg++), we tested whether in vivo concentrations of this ion are sufficient to suppress NMDA-receptor-mediated responses. We show that slow, local microinfusion of Mg(++)-free artificial cerebrospinal fluid onto noradrenergic locus coeruleus (LC) neurons reveals an NMDA-receptor-mediated component of their response to a sensory stimulus. This is the first demonstration that the in vivo concentration of extracellular Mg++ ions suppresses synaptically mediated NMDA receptor activation. We also present evidence that unmasking this NMDA receptor activity induces prolonged enhancement of the EAA-mediated sensory response of LC neurons.
Shiekhattar
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R
Department of Mental Health Sciences, Hahnemann University, Philadelphia, Pennsylvania 19102-1192.
Aston-Jones
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G
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000166:cytology* / Q000502:physiology; D004594:Electrophysiology; D066298:In Vitro Techniques; D008125:Locus Coeruleus / Q000166:cytology / Q000502:physiology; D008274:Magnesium / Q000494:pharmacology*; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism
D000596:Amino Acids; D016194:Receptors, N-Methyl-D-Aspartate; D008274:Magnesium; D009638:Norepinephrine