Cyclic-nucleotide–gated cation current and Ca<sup>2+</sup>-activated Cl current elicited by odorant in vertebrate olfactory receptor neurons

Li, Rong Chang; Ben-Chaim, Yair; Yau, King Wai; Lin, Chih Chun

doi:10.1073/pnas.1613891113

Cited by 26 publications

(31 citation statements)

References 69 publications

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“…2D, E). These results suggest that EOGs in Ano2 À/À mice originate from CNG channels and not from a CNG/Cl À channel combination as in wild-type mice Li et al 2016).…”

Section: Afferent Signal Amplification By Anoctaminmentioning

confidence: 70%

“…Additional information for understanding Cl À -based signal amplification came from single-ORN recordings. A recently developed method makes it possible to separate quantitatively cation currents from chloride currents during odor response (Li et al 2016). The study demonstrated that the ratio of currents through Ca 2+ -gated Cl À channels and CNG channels, I Cl /I cation , increased at low odor concentrations, an observation consistent with our finding that ANO2-mediated amplification is strongest at low stimulus intensities.…”

Section: Discussionmentioning

confidence: 99%

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Tracking of unfamiliar odors is facilitated by signal amplification through anoctamin 2 chloride channels in mouse olfactory receptor neurons

et al. 2017

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Many animals follow odor trails to find food, nesting sites, or mates, and they require only faint olfactory cues to do so. The performance of a tracking dog, for instance, poses the question on how the animal is able to distinguish a target odor from the complex chemical background around the trail. Current concepts of odor perception suggest that animals memorize each odor as an olfactory object, a percept that enables fast recognition of the odor and the interpretation of its valence. An open question still is how this learning process operates efficiently at the low odor concentrations that typically prevail when animals inspect an odor trail. To understand olfactory processing under these conditions, we studied the role of an amplification mechanism that boosts signal transduction at low stimulus intensities, a process mediated by calcium‐gated anoctamin 2 chloride channels. Genetically altered Ano2 −/− mice, which lack these channels, display an impaired cue‐tracking behavior at low odor concentrations when challenged with an unfamiliar, but not with a familiar, odor. Moreover, recordings from the olfactory epithelium revealed that odor coding lacks sensitivity and temporal resolution in anoctamin 2‐deficient mice. Our results demonstrate that the detection of an unfamiliar, weak odor, as well as its memorization as an olfactory object, require signal amplification in olfactory receptor neurons. This process may contribute to the phenomenal tracking abilities of animals that follow odor trails.

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“…2D, E). These results suggest that EOGs in Ano2 À/À mice originate from CNG channels and not from a CNG/Cl À channel combination as in wild-type mice Li et al 2016).…”

Section: Afferent Signal Amplification By Anoctaminmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Tracking of unfamiliar odors is facilitated by signal amplification through anoctamin 2 chloride channels in mouse olfactory receptor neurons

et al. 2017

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“…Finally, the Cl − current is the predominant component of the currents that depolarize ORNs [39,58] and is mediated by Ca 2+ -gated Cl − ion channels. This current response induced due to Ca 2+ is again a Hill function of coefficient greater than one, suggesting further cooperativity [81].…”

Section: Competitive Bindingmentioning

confidence: 99%

Antagonism in olfactory receptor neurons and its implications for the perception of odor mixtures

Reddy

Zak

Vergassola

et al. 2017

Preprint

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Natural environments feature mixtures of odorants of diverse quantities, qualities and complexities. Olfactory receptor neurons (ORNs) are the first layer in the sensory pathway and transmit the olfactory signal to higher regions of the brain. Yet, the response of ORNs to mixtures is strongly non-additive, and exhibits antagonistic interactions among odorants. Here, we model the processing of mixtures by mammalian ORNs, focusing on the role of inhibitory mechanisms. Theoretically predicted response curves capture experimentally determined glomerular responses imaged by a calcium indicator expressed in ORNs of live, breathing mice. Antagonism leads to an effective "normalization" of the ensemble glomerular response, which arises from a novel mechanism involving the distinct statistical properties of receptor binding and activation, without any recurrent neuronal circuitry. Normalization allows our encoding model to outperform noninteracting models in odor discrimination tasks, and to explain several psychophysical experiments in humans.

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“…Recently, we have developed in frog ORNs a protocol that successfully dissects the overall olfactory response into its CNG and Cl components (29). We found that, at least in frog, the Cl current is the major component throughout the dynamic range of the response, including near action-potential-signaling threshold to the brain (29).…”

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confidence: 99%

Ca ²⁺ -activated Cl current predominates in threshold response of mouse olfactory receptor neurons

Lin

Ren

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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In mammalian olfactory transduction, odorants activate a cAMP-mediated signaling pathway that leads to the opening of cyclic nucleotide-gated (CNG), nonselective cation channels and depolarization. The Ca influx through open CNG channels triggers an inward current through Ca-activated Cl channels (ANO2), which is expected to produce signal amplification. However, a study on an mouse line reported no elevation in the behavioral threshold of odorant detection compared with wild type (WT). Subsequent studies by others on the same line, nonetheless, found subtle defects in olfactory behavior and some abnormal axonal projections from the olfactory receptor neurons (ORNs) to the olfactory bulb. As such, the question regarding signal amplification by the Cl current in WT mouse remains unsettled. Recently, with suction-pipette recording, we have successfully separated in frog ORNs the CNG and Cl currents during olfactory transduction and found the Cl current to predominate in the response down to the threshold of action-potential signaling to the brain. For better comparison with the mouse data by others, we have now carried out similar current-separation experiments on mouse ORNs. We found that the Cl current clearly also predominated in the mouse olfactory response at signaling threshold, accounting for ∼80% of the response. In the absence of the Cl current, we expect the threshold stimulus to increase by approximately sevenfold.

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Cyclic-nucleotide–gated cation current and Ca²⁺-activated Cl current elicited by odorant in vertebrate olfactory receptor neurons

Cited by 26 publications

References 69 publications

Tracking of unfamiliar odors is facilitated by signal amplification through anoctamin 2 chloride channels in mouse olfactory receptor neurons

Tracking of unfamiliar odors is facilitated by signal amplification through anoctamin 2 chloride channels in mouse olfactory receptor neurons

Antagonism in olfactory receptor neurons and its implications for the perception of odor mixtures

Ca ²⁺ -activated Cl current predominates in threshold response of mouse olfactory receptor neurons

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Cyclic-nucleotide–gated cation current and Ca2+-activated Cl current elicited by odorant in vertebrate olfactory receptor neurons

Cited by 26 publications

References 69 publications

Tracking of unfamiliar odors is facilitated by signal amplification through anoctamin 2 chloride channels in mouse olfactory receptor neurons

Tracking of unfamiliar odors is facilitated by signal amplification through anoctamin 2 chloride channels in mouse olfactory receptor neurons

Antagonism in olfactory receptor neurons and its implications for the perception of odor mixtures

Ca 2+ -activated Cl current predominates in threshold response of mouse olfactory receptor neurons

Contact Info

Product

Resources

About

Cyclic-nucleotide–gated cation current and Ca²⁺-activated Cl current elicited by odorant in vertebrate olfactory receptor neurons

Ca ²⁺ -activated Cl current predominates in threshold response of mouse olfactory receptor neurons