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Odorant-specific modes of signaling in mammalian olfaction.

Odors play an important role in our quality of life and well being, a role that is compromised by the effect of disease, drugs, aging, and environmental onslaught on the olfactory epithelium (OE). Olfactory receptor neurons (ORNs) in OE provide the primary input to the olfactory system, such that disruption of the cellular processes leading to the activation of the ORNs inevitably compromises olfactory function. The organization of the olfactory periphery in mammals is emerging to be more complex than originally thought. An often underappreciated aspect of that complexity is that odorants have 2 odorant-specific modes of signaling, that is, they inhibit as well as excite the ORNs. The ubiquity of this phenomenon across diverse animal species suggests that having opponent input into the olfactory system is fundamental to how olfaction works, yet in contrast to our canonical understanding of how odorants excite mammalian ORNs, our understanding of how odorants inhibit these cells is still unclear. Odorants potentially can inhibit ORNs through multiple not necessarily mutually exclusive mechanisms but compelling new data argue that phosphoinositide (PI) signaling at least in part mediates inhibitory odorant input to mammalian ORNs. The idea that inhibitory input is mediated through a distinct input pathway argues for the fundamental importance of inhibitory input to olfactory coding in mammals and identifies an additional possible cellular basis for olfactory dysfunction.