Expression of the NMDA receptor subunit GluN3A (NR3A) in the olfactory system and its regulatory role on olfaction in the adult mouse.
Glutamate is an excitatory neurotransmitter in the olfactory system and its N-methyl-D-aspartate-(NMDA) receptor subunits [GluN1 (NR1), GluN2A (NR2A), and GluN2B (NR2B)] are expressed at synapses in the olfactory bulb and olfactory epithelium. Thus, glutamatergic neurons and NMDA receptors play key roles in olfaction. GluN3A (NR3A) is a unique inhibitory subunit in the NMDA receptor complex; however, the expression and functional role of GluN3A in the olfactory bulb and epithelium remain unclear. The present study examined the expression patterns of GluN3A in the olfactory bulb and epithelium and explored its functional role in the olfactory system. Immunohistochemical and Western blot analyses revealed that GluN3A is abundantly expressed in different cellular layers of the olfactory bulb and epithelium of the adult wild type (WT) mice. In littermate GluN3A knockout (GluN3A(-/-); KO) mice, the expression of olfactory marker protein normally found in mature olfactory sensory neurons was significantly reduced in the olfactory bulb and epithelium. A butyl alcohol stimulus increased immediate-early gene c-Fos expression in the olfactory system of WT mice, while this response was absent in GluN3A KO mice. The level of phosphorylated Ca(2+)/calmodulin-dependent kinase II was significantly lower in GluN3A KO mice compared to WT mice. In buried food finding test, GluN3A mice took significantly longer time to find food compared to WT mice. Consistently, impaired odor distinguishing ability was seen in GluN3A KO mice. These findings suggest that GluN3A, expressed in the adult olfactory system, plays a significant regulatory role in olfactory development and functional activity.
Department of Anesthesiology, Emory University School of Medicine, 101 Woodruff Circle, WMB suite 620, Atlanta, GA, 30322, USA.|Center for Visual and Neurocognitive Rehabilitation, VA Medical Center, Decatur, GA, 30033, USA.
Jin Hwan
JH
Lee
Department of Anesthesiology, Emory University School of Medicine, 101 Woodruff Circle, WMB suite 620, Atlanta, GA, 30322, USA.|Department of Neurology, Emory University School of Medicine, Atlanta, GA, 30322, USA.
Ling
L
Wei
Department of Anesthesiology, Emory University School of Medicine, 101 Woodruff Circle, WMB suite 620, Atlanta, GA, 30322, USA.
Todd C
TC
Deveau
Department of Anesthesiology, Emory University School of Medicine, 101 Woodruff Circle, WMB suite 620, Atlanta, GA, 30322, USA.|Center for Visual and Neurocognitive Rehabilitation, VA Medical Center, Decatur, GA, 30033, USA.
Xiaohuan
X
Gu
Department of Anesthesiology, Emory University School of Medicine, 101 Woodruff Circle, WMB suite 620, Atlanta, GA, 30322, USA. spyu@emory.edu.|Center for Visual and Neurocognitive Rehabilitation, VA Medical Center, Decatur, GA, 30033, USA. spyu@emory.edu.
Shan Ping
SP
Yu
D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D009830:Olfactory Bulb / Q000378:metabolism*; D051842:Olfactory Marker Protein / Q000378:metabolism; D009831:Olfactory Mucosa / Q000378:metabolism*; D055696:Olfactory Perception / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D012903:Smell / Q000502:physiology*
C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; C584082:GluN3A protein, mouse; D051842:Olfactory Marker Protein; C497598:Omp protein, mouse; D016760:Proto-Oncogene Proteins c-fos; D016194:Receptors, N-Methyl-D-Aspartate; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2
GluN3A (NR3A); NMDA; Olfaction; Olfactory bulb; Olfactory epithelium