Olfactory receptor and neural pathway responsible for highly selective sensing of musk odors

Mika Shirasu; Keiichi Yoshikawa; Yoshiki Takai; Ai Nakashima; Haruki Takeuchi; Hitoshi Sakano; Kazushige Touhara

doi:10.1016/j.neuron.2013.10.021

Olfactory receptor and neural pathway responsible for highly selective sensing of musk odors

Neuron. 2014 Jan 8;81(1):165-78. doi: 10.1016/j.neuron.2013.10.021. Epub 2013 Dec 19.

Authors

Mika Shirasu¹, Keiichi Yoshikawa², Yoshiki Takai², Ai Nakashima³, Haruki Takeuchi³, Hitoshi Sakano³, Kazushige Touhara⁴

Affiliations

¹ Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan; ERATO Touhara Chemosensory Signal Project, JST, The University of Tokyo, Tokyo 113-8657, Japan.
² Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan.
³ Department of Brain Function, School of Medical Science, University of Fukui, Fukui 910-1193, Japan.
⁴ Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan; ERATO Touhara Chemosensory Signal Project, JST, The University of Tokyo, Tokyo 113-8657, Japan. Electronic address: ktouhara@mail.ecc.u-tokyo.ac.jp.

PMID: 24361078
DOI: 10.1016/j.neuron.2013.10.021

Abstract

Musk odorants are used widely in cosmetic industries because of their fascinating animalic scent. However, how this aroma is perceived in the mammalian olfactory system remains a great mystery. Here, we show that muscone, one musk odor secreted by various animals from stink glands, activates a few glomeruli clustered in a neuroanatomically unique anteromedial olfactory bulb. The muscone-responsive glomeruli are highly specific to macrocyclic ketones; interestingly, other synthetic musk odorants with nitro or polycyclic moieties or ester bonds activate distinct but nearby glomeruli. Anterodorsal bulbar lesions cause muscone anosmia, suggesting that this region is involved in muscone perception. Finally, we identified the mouse olfactory receptor, MOR215-1, that was a specific muscone receptor expressed by neurons innervating the muscone-responsive anteromedial glomeruli and also the human muscone receptor, OR5AN1. The current study documents the olfactory neural pathway in mice that senses and transmits musk signals from receptor to brain.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Colforsin / pharmacology
Cycloparaffins / pharmacology
Dose-Response Relationship, Drug
Fatty Acids, Monounsaturated*
Gene Expression Regulation / drug effects
Gene Expression Regulation / genetics
Green Fluorescent Proteins / genetics
Green Fluorescent Proteins / metabolism
Humans
Membrane Potentials / drug effects
Membrane Potentials / genetics
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neural Cell Adhesion Molecules / metabolism
Odorants
Olfactory Bulb / cytology*
Olfactory Bulb / surgery
Olfactory Pathways / drug effects
Olfactory Pathways / physiology*
Olfactory Receptor Neurons / drug effects
Olfactory Receptor Neurons / physiology*
Proto-Oncogene Proteins c-fos / metabolism
Receptors, Odorant / genetics
Smell / drug effects
Smell / physiology*
Xenopus laevis

Substances

Cycloparaffins
Fatty Acids, Monounsaturated
Ncam2 protein, mouse
Neural Cell Adhesion Molecules
OR52A1 protein, human
Proto-Oncogene Proteins c-fos
Receptors, Odorant
enhanced green fluorescent protein
musk
Green Fluorescent Proteins
Colforsin
muscone