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The ciliary localized GPCR, MCHR1, modulates odor responses in the olfactory bulb
Author(s) -
McIntyre Jeremy C.,
Jasson Kalene,
Ross Jordan,
Fletcher Max,
Reed Randy
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.06910
Subject(s) - olfactory bulb , mcherry , cilium , microbiology and biotechnology , olfactory system , biology , receptor , neuroscience , olfactory receptor , central nervous system , gene , genetics , green fluorescent protein
The sense of smell is essential for maintaining full human health and quality of life. It plays an important role in the detection of environmental dangers as well guiding decisions such as what foods to eat. However, olfactory processing is influenced by the physiological state of an organism. Physiological changes such can be integrated in the hypothalamus, through populations of neurons expressing various neuropeptides. One of these peptides is melanin‐concentrating hormone (MCH) which functions in both promoting feeding and sleep. Neurons expressing MCH project to several areas of the brain including the olfactory bulb (OB), where the MCH receptor, MCHR1, a g‐protein coupled receptor, is expressed. MCH signaling has been implicated in olfactory driven behaviors, however the mechanism by which it does so is unknown. In rodents, there is a single MCH receptor, MCHR1, which is enriched in neuronal primary cilia. To better understand the mechanism by which MCHR1 signaling affects olfactory behaviors we have first analyzed its distribution in the OB. Using antibody labeling, we find that MCHR1 localizes to cilia of interneurons in the granule cell and glomerular layers. To further confirm this, and generate a potential tool for future studies, we used CRISPR/CAS9 to fuse mCherry to the n‐terminus of MCHR1 (mCherry:MCHR1). Expression of mCherry:MCHR1 matches that of endogenous MCHR1, localizing to the primary cilium of granule cells and a subset of periglomerular cells. MCHR1, and mCherry:MCHR1, is not detected in the primary cilia of mitral cells, the primary output neurons of the olfactory bulb. To test the neuromodulatory role of MCHR1 in olfactory signaling, we have performed functional imaging experiments of the OB in response to odorant stimulation. Using epifluorescence calcium imaging, we find that glomerular responses of mitral/tufted cells are enhanced following administration of an MCHR1 antagonist, SNAP‐94847, (t(157) = 5.425, p <0.0001) while application of MCH decreases glomerular responses (t(99) = 10.98, p <0.0001). Together these data suggest that the ciliary GPCR, MCHR1 contributes to modulation of olfactory function. Furthermore, our newly generated mouse line will aid in studying the role of MCHR1 in other brain regions and will aid in determining the importance of ciliary localization of specific GPCRs in modulating neuronal function. Support or Funding Information Support was provided by R00DC013555 and pilot grans from the University of Florida Center for Smell and Taste, and a UF MBI pilot project (JCM), T32DC015994 (KRJ) F31DC 016485 (JMR) and R01DC004553 (RRR)