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Curr Biol

Title:		Odorant Receptor Inhibition Is Fundamental to Odor Encoding
Author(s):		Pfister P; Smith BC; Evans BJ; Brann JH; Trimmer C; Sheikh M; Arroyave R; Reddy G; Jeong HY; Raps DA; Peterlin Z; Vergassola M; Rogers ME;
Address:		"Firmenich Incorporated, 250 Plainsboro Road, Plainsboro, NJ 08536, USA. Department of Physics, UC San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA. Firmenich Incorporated, 250 Plainsboro Road, Plainsboro, NJ 08536, USA. Electronic address: matthew.rogers@firmenich.com"
Journal Title:		Curr Biol
Year:		2020
Volume:		20200528
Issue:		13
Page Number:		2574 - 2587
DOI:		10.1016/j.cub.2020.04.086
ISSN/ISBN:		1879-0445 (Electronic) 0960-9822 (Linking)
Abstract:		"Most natural odors are complex mixtures of volatile components, competing to bind odorant receptors (ORs) expressed in olfactory sensory neurons (OSNs) of the nose. To date, surprisingly little is known about how OR antagonism shapes neuronal representations in the detection layer of the olfactory system. Here, we investigated its prevalence, the degree to which it disrupts OR ensemble activity, and its conservation across phylogenetically related ORs. Calcium imaging microscopy of dissociated OSNs revealed significant inhibition, often complete attenuation, of responses to indole-a commonly occurring volatile associated with both floral and fecal odors-by a set of 36 tested odorants. To confirm an OR mechanism for the observed inhibition, we performed single-cell transcriptomics on OSNs exhibiting specific response profiles to a diagnostic panel of odorants and identified three paralogous receptors-Olfr740, Olfr741, and Olfr743-which, when tested in vitro, recapitulated OSN responses. We screened ten ORs from the Olfr740 gene family with approximately 800 perfumery-related odorants spanning a range of chemical scaffolds and functional groups. Over half of these compounds (430) antagonized at least one of the ten ORs. OR activity fitted a mathematical model of competitive receptor binding and suggests normalization of OSN ensemble responses to odorant mixtures is the rule rather than the exception. In summary, we observed OR antagonism occurred frequently and in a combinatorial manner. Thus, extensive receptor-mediated computation of mixture information appears to occur in the olfactory epithelium prior to transmission of odor information to the olfactory bulb"
Keywords:		"Animals Gene Expression Profiling Male Mice Mice, Inbred C57BL Mice, Transgenic Odorants/*analysis Olfactory Perception/*physiology Olfactory Receptor Neurons/drug effects/*physiology Receptors, Odorant/*antagonists & inhibitors Single-Cell Analysis *Tran;"
Notes:		"MedlinePfister, Patrick Smith, Benjamin C Evans, Barry J Brann, Jessica H Trimmer, Casey Sheikh, Mushhood Arroyave, Randy Reddy, Gautam Jeong, Hyo-Young Raps, Daniel A Peterlin, Zita Vergassola, Massimo Rogers, Matthew E eng Research Support, Non-U.S. Gov't England 2020/05/30 Curr Biol. 2020 Jul 6; 30(13):2574-2587.e6. doi: 10.1016/j.cub.2020.04.086. Epub 2020 May 28"