title: An Olfactory Cilia Pattern in the Mammalian Nose Ensures High Sensitivity to Odors.
abstract: In many sensory organs, specialized receptors are strategically arranged to enhance detection sensitivity and acuity. It is unclear whether the olfactory system utilizes a similar organizational scheme to facilitate odor detection. Curiously, olfactory sensory neurons (OSNs) in the mouse nose are differentially stimulated depending on the cell location. We therefore asked whether OSNs in different locations evolve unique structural and/or functional features to optimize odor detection and discrimination. Using immunohistochemistry, computational fluid dynamics modeling, and patch clamp recording, we discovered that OSNs situated in highly stimulated regions have much longer cilia and are more sensitive to odorants than those in weakly stimulated regions. Surprisingly, reduction in neuronal excitability or ablation of the olfactory G protein in OSNs does not alter the cilia length pattern, indicating that neither spontaneous nor odor-evoked activity is required for its establishment. Furthermore, the pattern is evident at birth, maintained into adulthood, and restored following pharmacologically induced degeneration of the olfactory epithelium, suggesting that it is intrinsically programmed. Intriguingly, type III adenylyl cyclase (ACIII), a key protein in olfactory signal transduction and ubiquitous marker for primary cilia, exhibits location-dependent gene expression levels, and genetic ablation of ACIII dramatically alters the cilia pattern. These findings reveal an intrinsically programmed configuration in the nose to ensure high sensitivity to odors.
authors.affiliation: Department of Neuroscience, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Rosemary C
authors.initials: RC
authors.lastname: Challis
authors.affiliation: Department of Neuroscience, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Huikai
authors.initials: H
authors.lastname: Tian
authors.affiliation: Department of Neuroscience, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Jue
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Neuroscience, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Jiwei
authors.initials: J
authors.lastname: He
authors.affiliation: Monell Chemical Senses Center, Philadelphia, PA 19104, USA.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Pharmacology, University of Washington School of Medicine, Seattle, WA 98195, USA.
authors.forename: Xuanmao
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Neuroscience, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Geriatrics, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Yin
authors.affiliation: Department of Neuroscience, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Connelly
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors.forename: Limei
authors.initials: L
authors.lastname: Ma
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors.forename: C Ron
authors.initials: CR
authors.lastname: Yu
authors.affiliation: Department of Physiology, Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Pluznick
authors.affiliation: Department of Pharmacology, University of Washington School of Medicine, Seattle, WA 98195, USA.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Storm
authors.affiliation: Monell Chemical Senses Center, Philadelphia, PA 19104, USA; College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang 315008, China.
authors.forename: Liquan
authors.initials: L
authors.lastname: Huang
authors.affiliation: Monell Chemical Senses Center, Philadelphia, PA 19104, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhao
authors.affiliation: Department of Neuroscience, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. Electronic address: minghong@mail.med.upenn.edu.
authors.forename: Minghong
authors.initials: M
authors.lastname: Ma
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D008953:Models, Anatomic; D008954:Models, Biological; D009297:Nasal Mucosa / Q000378:metabolism; D009666:Nose / Q000502:physiology*; D009812:Odorants; D018034:Olfactory Receptor Neurons / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D012903:Smell / Q000502:physiology*
chemical_list: D000262:Adenylyl Cyclases; C421784:adenylate cyclase 3
keywords: airflow; computational fluid dynamics model; odorant absorption; olfactory cilia; patch clamp; type III adenylyl cyclase