Nucleus-specific expression of ionotropic glutamate receptor subunit mRNAs and binding sites in primate thalamus.
Thalamic afferents and efferents utilize glutamate as their primary neurotransmitter. There are four families of glutamate receptors that can transduce this activity, as well as regulate glutamate release from thalamic relay neurons. The three ionotropic subtypes are of particular importance, because subunit composition confers variability in functional properties of each subtype. We have quantified the expression of NMDA, AMPA and kainate receptors in the thalamus of the macaque using receptor autoradiography and in situ hybridization. NMDA receptors are multimeric associations of NR1 and NR2A-NR2D subunits that form ligand-gated ion channels. Particular subunits are associated with modulatory binding sites that affect receptor activity. NR1 was the most abundant subunit mRNA; NR2A, NR2B, and NR2D subunit mRNAs were also present, but were expressed in nucleus-specific patterns. Very high levels of [3H]ifenprodil binding to the polyamine site of the NMDA complex were detected in a fairly homogeneous distribution. Binding of the ion channel ligand [3H]MK-801 was also abundant, and limbic nuclei expressed higher levels than motor nuclei or the reticular nucleus. [3H]CGP39653 binding to the glutamate site of the NMDA receptor was the least abundant of the NMDA receptor binding sites. There was variability in the stoichiometric relationships of binding sites across nuclei, suggesting that there is heterogeneity in the pharmacological properties of NMDA receptors expressed in the thalamus. AMPA and kainate are also multimeric associations of specific subunits that form ligand-gated ion channels. These subunits are encoded by specific genes: gluR1-gluR4 for AMPA receptors, and gluR5-gluR7 and KA1-KA2 for kainate receptors. GluR4 and gluR6 mRNAs were, respectively the most abundant of the AMPA and kainate receptor subunit transcripts. Both AMPA and kainate receptor subunit transcripts were expressed in a nucleus-specific pattern. The binding of [3H]kainate was higher than that of [3H]AMPA throughout the thalamus, but AMPA subunit mRNA levels were three to five orders of magnitude higher than those encoding the kainate receptor subunits. The mismatch between the levels of expression of kainate receptor subunit transcripts and binding sites is suggestive of a presynaptic localization of kainate receptors on thalamic afferents. These results suggest that ionotropic glutamate receptors are heterogeneously expressed in the thalamus of the primate, and that their differential expression is both subunit- and nucleus-specific.
Mental Health Research Institute and Department of Psychiatry, University of Michigan, 48109, Ann Arbor 48109, USA.
H M
HM
Ibrahim
D J
DJ
Healy
A J
AJ
Hogg
J H
JH
Meador-Woodruff
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D016291:Dizocilpine Maleate / Q000493:pharmacokinetics; D018691:Excitatory Amino Acid Antagonists / Q000493:pharmacokinetics; D008254:Macaca nemestrina; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009928:Organ Specificity; D010880:Piperidines / Q000493:pharmacokinetics; D012333:RNA, Messenger / Q000032:analysis; D018091:Receptors, AMPA / Q000235:genetics* / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000235:genetics* / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics* / Q000378:metabolism*; D013787:Thalamic Nuclei / Q000166:cytology / Q000378:metabolism*; D014158:Transcription, Genetic; D014316:Tritium
D015763:2-Amino-5-phosphonovalerate; D016291:Dizocilpine Maleate; D018691:Excitatory Amino Acid Antagonists; D010880:Piperidines; D012333:RNA, Messenger; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D014316:Tritium; C069052:CGP 39653; C010739:ifenprodil