N-methyl- d-aspartate induces regular firing patterns in the cat lateral habenula in vivo

Abstract

The present study was undertaken to elucidate the action of excitatory amino acids in the dorsal diencephalic pathway. Single neurons in the lateral habenula of halothane-anesthetized cats were recorded extracellularly, and excitatory amino acid receptor agonists and antagonists were applied by iontophoresis. Most neurons in the lateral habenula were spontaneously active. This spontaneous firing could be inhibited by kynurenic acid, a broad spectrum antagonist of excitatory amino acid receptors, but not by the selective N-methyl- d-aspartate receptor antagonist 2-amino-7-phosphono-heptanoic acid. Iontophoretic application of α-amino-3-hydroxy-5-methyl-5-isoxazolepropionate, quisqualate and kainate mostly elicited a non-burst, regular firing pattern which was sensitive to kynurenic acid. Surprisingly, 116 (96%) out of 121 neurons in the lateral habenula responded to iontophoretic application of N-methyl- d-aspartate with a regular non-burst firing pattern, in contrast to previously published observations from other brain regions where N-methyl- d-aspartate predominantly elicited phasic firing patterns. When cells were recorded with electrode assemblies where one iontophoretic barrel contained MgCl 2 or MgSO 4, only 10 (43%) out of 23 cells responded with regular firing upon application of N-methyl- d-aspartate, while 13 (57%) now displayed a phasic firing pattern. In these cells iontophoretically applied α-amino-3-hydroxy-5 methyl-5-isoxazolepropionate or quisqualate still evoked only regular firing. In a few cases, an initially regular N-methyl- d-aspartate-induced firing pattern could be changed to a phasic pattern following active ejection of Mg 2+ ions. The ability of lateral habenula neurons to switch from tonic to phasic firing patterns could increase the efficacy of neurotransmission through the dorsal diencephalic pathway.