fMRI study of the role of glutamate NMDA receptor in the olfactory processing in monkeys

• Published in: PloS one Vol. 13; no. 6; p. e0198395
• Main Authors: Zhao, Fuqiang, Holahan, Marie A, Wang, Xiaohai, Uslaner, Jason M, Houghton, Andrea K, Evelhoch, Jeffrey L, Winkelmann, Christopher T, Hines, Catherine D G
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 05.06.2018; Public Library of Science (PLoS)
• Subjects: Acetic acid; Analysis; Animals; Attenuation; Biology and Life Sciences; Blood; Blood volume; Cerebral blood flow; Cerebral Blood Volume; Cortex (olfactory); Cortex (piriform); Dizocilpine Maleate - pharmacology; Female; Functional magnetic resonance imaging; Glutamate; Glutamic acid receptors (ionotropic); Health aspects; Information processing; Injection; Interneurons; Isoamyl acetate; Laboratory animals; Macaca mulatta; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Medicine and Health Sciences; Monkeys; N-methyl-D-aspartate; N-Methyl-D-aspartic acid receptors; Neurons; NMR; Nuclear magnetic resonance; Odor; Odors; Olfactory bulb; Olfactory Bulb - diagnostic imaging; Olfactory Bulb - metabolism; Olfactory Cortex - diagnostic imaging; Olfactory Cortex - metabolism; Olfactory Perception - physiology; Olfactory system; Pentanols - pharmacology; Physiological aspects; Primates; Receptors; Receptors, N-Methyl-D-Aspartate - metabolism; Research and Analysis Methods; Rodents; Sensory stimulation; Smell; Studies; United States > US; Pennsylvania
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0198395

Studies in rodents show that olfactory processing in the principal neurons of olfactory bulb (OB) and piriform cortex (PC) is controlled by local inhibitory interneurons, and glutamate NMDA receptor plays a role in this inhibitory control. It is not clear if findings from studies in rodents translate to olfactory processing in nonhuman primates (NHPs). In this study, the effect of the glutamate NMDA receptor antagonist MK801 on odorant-induced olfactory responses in the OB and PC of anesthetized NHPs (rhesus monkeys) was investigated by cerebral blood volume (CBV) fMRI. Isoamyl-acetate was used as the odor stimulant. For each NHP, sixty fMRI measurements were made during a 4-h period, with each 4-min measurement consisting of a 1-min baseline period, a 1-min odor stimulation period, and a 2-min recovery period. MK801 (0.3 mg/kg) was intravenously delivered 1 hour after starting fMRI. Before MK801 injection, olfactory fMRI activations were observed only in the OB, not in the PC. After MK801 injection, olfactory fMRI activations in the OB increased, and robust olfactory fMRI activations were observed in the PC. The data indicate that MK801 enhances the olfactory responses in both the OB and PC. The enhancement effects of MK801 are most likely from its blockage of NMDA receptors on local inhibitory interneurons and the attenuation of the inhibition onto principal neurons. This study suggests that the mechanism of local inhibitory control of principal neurons in the OB and PC derived from studies in rodents translates to NHPs.