Abstract
Mammalian urine releases complex mixtures of volatile compounds that are used in reproduction, territoriality and conspecific recognition. To understand how such complex mixtures are represented in the main olfactory bulb, we analysed the electrophysiological responses of individual mitral cells to volatile compounds in mouse urine. In both males and females, urine volatile compounds evoke robust responses in a small subset of mitral cells. Fractionation of the volatile compounds using gas chromatography showed that out of the hundreds of compounds present, mitral cells are activated by single compounds. One cohort of mitral cells responded exclusively to male urine; these neurons were activated by (methylthio)methanethiol, a potent, previously unknown semiochemical present only in male urine. When added to urine, synthetic (methylthio)methanethiol significantly enhances urine attractiveness to female mice. We conclude that mitral cells represent natural odorant stimuli by acting as selective feature detectors, and that their activation is largely independent of the presence of other components in the olfactory stimulus.
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Acknowledgements
We thank R. Axel, M. Ehlers, R. Mooney, D. Fitzpatrick and members of the Katz laboratory for critical comments on the manuscript; J. Jin, R. Irving, G. Dubay and L. Nielsen for technical assistance; and X. Han for critical assistance with chemical analysis. This work is supported by the NIH (NICDS) (L.C.K.), the Broad Foundation (D.Y.L.), NSF (E.B.), the Petroleum Research Fund, administered by the American Chemical Society (E.B.), and the Berryman Institute (E.B.). L.C.K. is an Investigator in the Howard Hughes Medical Institute.
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Supplementary information
Supplementary Methods
This file contains details on constructing cell response map and synthesis of (methylthio)methanethiol. (DOC 28 kb)
Supplementary Figure S1
Clustered organization of urine responsive neurons in the main olfactory bulb. (PPT 263 kb)
Supplementary Figure S2
Optical imaging of intrinsic signals reveals no glomerular activation in response to urine odour on dorsal surface of the MOB. (PPT 4482 kb)
Supplementary Figure S3
Schematic representation of a gas chromatography-electrophysiology (GC-E) experiment. (PPT 80 kb)
Supplementary Figure S4
Urine responsive cells activated by multiple compounds in urine. (PPT 340 kb)
Supplementary Figure S5
Averaging multiple GC runs does not reveal the presence of additional weak responses. (PPT 608 kb)
Supplementary Figure S6
Separated compounds present in urine provide a rich source of odourant stimuli detectable by human observers. (PPT 94 kb)
Supplementary Figure S7
The pheromone 6-hydoxy-6-methyl-3-heptanone (6H6M3H) is not responsible for excitation of male-urine selective mitral cells. (PPT 195 kb)
Supplementary Figure S8
Scatter plots comparing the investigation times for intact, castrated and MTMT-containing urine. (PPT 58 kb)
Supplementary Figure S9
Neuronal responses elicited by MTMT are independent of other components in castrated mouse urine. (PPT 559 kb)
Supplementary Figure Legends
Legends to accompany the above Supplementary Figures S1-S9. (DOC 36 kb)
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Lin, D., Zhang, SZ., Block, E. et al. Encoding social signals in the mouse main olfactory bulb. Nature 434, 470–477 (2005). https://doi.org/10.1038/nature03414
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DOI: https://doi.org/10.1038/nature03414
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