NMDA-receptor modulation of lateral inhibition and c-fos expression in olfactory bulb.
Olfactory bulb primary output neurons, mitral/tufted cells, are glutamatergic and excite inhibitory interneurons, granule cells, by activation of both alpha-amino-3-hydroxy-5-methyl-ioxazole-4-propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) glutamate receptors. The data presented here demonstrate that the NMDA antagonists MK-801 and CGP39551, but not ketamine, significantly enhanced expression of c-fos mRNA by mitral cells as measured by in situ hybridization. All three antagonists significantly reduced mitral/tufted cell excitation of granule cells as measured with extracellular field potentials following antidromic stimulation of the lateral olfactory tract (LOT). In turn, the NMDA antagonists significantly reduced granule cell mediated feedback inhibition of mitral/tufted cells, as measured with field potential recordings of paired-pulse LOT stimulation, suppression of mitral/tufted cell single-unit spontaneous activity following LOT stimulation, and intracellularly recorded IPSP amplitude in mitral/tufted cells following LOT stimulation. While there was not a perfect correlation between the effects of the NMDA antagonists on c-fos mRNA expression and on inhibition, the results suggest that disinhibition of mitral/tufted cells accounts for the observed enhancement in c-fos mRNA expression induced by NMDA receptor antagonists.
Wilson
D A
DA
Department of Zoology, University of Oklahoma, Norman 73019, USA.
Sullivan
R M
RM
Gall
C M
CM
Guthrie
K M
KM
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects*; D009830:Olfactory Bulb / Q000187:drug effects* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D018691:Excitatory Amino Acid Antagonists; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; C064540:CGP 39551; D007649:Ketamine; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate