Peripheral modulation of smell: Fact or fiction?

Despite studies dating back 30 or more years showing modulation of odorant responses at the level of the olfactory epithelium, most descriptions of the olfactory system infer that odorant signals make their way from detection by cilia on olfactory sensory neurons to the olfactory bulb unaltered. Recent identification of multiple subtypes of microvillar cells and identification of neuropeptide and neurotransmitter expression in the olfactory mucosa add to the growing body of literature for peripheral modulation in the sense of smell. Complex mechanisms including perireceptor events, modulation of sniff rates, and changes in the properties of sensory neurons match the sensitivity of olfactory sensory neurons to the external odorant environment, internal nutritional status, reproductive status, and levels of arousal or stress. By furthering our understanding of the players mediating peripheral olfaction, we may open the door to novel approaches for modulating the sense of smell in both health and disease.

► Our current view of peripheral olfactory processing is changing rapidly. ► Neurotransmitters released by extrinsic innervation modulate odor sensitivity. ► Many neuromodulators are synthesized and released within the olfactory mucosa. ► Peripheral smell modulation matches odor sensitivity to internal and external states. ► Understanding the complexities of peripheral modulation generates novel therapeutics.