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

PLoS One. 2018 Jun 5;13(6):e0198395. doi: 10.1371/journal.pone.0198395. eCollection 2018.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebral Blood Volume
  • Dizocilpine Maleate / pharmacology
  • Female
  • Macaca mulatta
  • Magnetic Resonance Imaging / methods*
  • Olfactory Bulb / diagnostic imaging*
  • Olfactory Bulb / metabolism
  • Olfactory Cortex / diagnostic imaging*
  • Olfactory Cortex / metabolism
  • Olfactory Perception / physiology*
  • Pentanols / pharmacology
  • Receptors, N-Methyl-D-Aspartate / metabolism*

Substances

  • Pentanols
  • Receptors, N-Methyl-D-Aspartate
  • Dizocilpine Maleate
  • isoamyl acetate

Grants and funding

All authors are current or former employees of Merck & Co., Inc., which is the funder of this work. Merck & Co., Inc. provided support in the form of salaries for all authors, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the `author contributions' section.