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

2017 ◽  
Vol 5 (15) ◽  
pp. e13373 ◽  
Author(s):  
Franziska Neureither ◽  
Nadine Stowasser ◽  
Stephan Frings ◽  
Frank Möhrlen
Keyword(s):  
Olfactory Receptor ◽  
Signal Amplification ◽  
Chloride Channels ◽  
Olfactory Receptor Neurons ◽  
Receptor Neurons

scholarly journals Calcium-activated chloride channels clamp odor-evoked spike activity in olfactory receptor neurons

2018 ◽  
Author(s):  
Joseph D. Zak ◽  
Julien Grimaud ◽  
Rong-Chang Li ◽  
Chih-Chun Lin ◽  
Venkatesh N. Murthy
Keyword(s):  
Olfactory Receptor ◽  
Chloride Channels ◽  
Feedback Mechanism ◽  
Olfactory Receptor Neurons ◽  
Odor Source ◽  
Wild Type ◽  
Behavioral Deficits ◽  
Receptor Neurons

AbstractThe calcium-activated chloride channel anoctamin-2 (Ano2) is thought to amplify transduction currents in ORNs, a hypothesis supported by previous studies in dissociated neurons from Ano2-/- mice. Paradoxically, despite a reduction in transduction currents in Ano2-/- ORNs, their spike output for odor stimuli may be higher. We examined the role of Ano2 in ORNs in their native environment in freely breathing mice by imaging activity in ORN axons as they arrive in the olfactory bulb glomeruli. Odor-evoked responses in ORN axons of Ano2-/- mice were consistently larger for a variety of odorants and concentrations. In an open arena, Ano2-/- mice took longer to approach a localized odor source than wild-type mice, revealing clear olfactory behavioral deficits. Our studies provide the first in vivo evidence toward an alternative role for Ano2 in the olfactory transduction cascade, where it may serve as a feedback mechanism to clamp ORN spike output.

scholarly journals Ca2+-activated Cl− current ensures robust and reliable signal amplification in vertebrate olfactory receptor neurons

2018 ◽  
Vol 116 (3) ◽  
pp. 1053-1058 ◽  
Author(s):  
Johannes Reisert ◽  
Jürgen Reingruber
Keyword(s):  
Olfactory Receptor ◽  
Signal Amplification ◽  
Olfactory Receptor Neuron ◽  
Olfactory Receptor Neurons ◽  
Ion Concentration ◽  
Modeling And Simulations ◽  
Small Space ◽  
Receptor Neurons ◽  
Concentration Changes ◽  
Transduction Current

Activation of most primary sensory neurons results in transduction currents that are carried by cations. One notable exception is the vertebrate olfactory receptor neuron (ORN), where the transduction current is carried largely by the anion Cl−. However, it remains unclear why ORNs use an anionic current for signal amplification. We have sought to provide clarification on this topic by studying the so far neglected dynamics of Na+, Ca2+, K+, and Cl− in the small space of olfactory cilia during an odorant response. Using computational modeling and simulations we compared the outcomes of signal amplification based on either Cl− or Na+ currents. We found that amplification produced by Na+ influx instead of a Cl− efflux is problematic for several reasons: First, the Na+ current amplitude varies greatly, depending on mucosal ion concentration changes. Second, a Na+ current leads to a large increase in the ciliary Na+ concentration during an odorant response. This increase inhibits and even reverses Ca2+ clearance by Na+/Ca2+/K+ exchange, which is essential for response termination. Finally, a Na+ current increases the ciliary osmotic pressure, which could cause swelling to damage the cilia. By contrast, a transduction pathway based on Cl− efflux circumvents these problems and renders the odorant response robust and reliable.

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

2016 ◽  
Vol 113 (40) ◽  
pp. 11078-11087 ◽  
Author(s):  
Rong-Chang Li ◽  
Yair Ben-Chaim ◽  
King-Wai Yau ◽  
Chih-Chun Lin
Keyword(s):  
Cyclic Nucleotide ◽  
Olfactory Receptor ◽  
Signal Amplification ◽  
Time Course ◽  
Olfactory Receptor Neurons ◽  
Cation Current ◽  
Nonselective Cation Channels ◽  
Predominant Component ◽  
Receptor Neurons ◽  
The Brain

Olfactory transduction in vertebrate olfactory receptor neurons (ORNs) involves primarily a cAMP-signaling cascade that leads to the opening of cyclic-nucleotide–gated (CNG), nonselective cation channels. The consequent Ca2+ influx triggers adaptation but also signal amplification, the latter by opening a Ca2+-activated Cl channel (ANO2) to elicit, unusually, an inward Cl current. Hence the olfactory response has inward CNG and Cl components that are in rapid succession and not easily separable. We report here success in quantitatively separating these two currents with respect to amplitude and time course over a broad range of odorant strengths. Importantly, we found that the Cl current is the predominant component throughout the olfactory dose–response relation, down to the threshold of signaling to the brain. This observation is very surprising given a recent report by others that the olfactory-signal amplification effected by the Ca2+-activated Cl current does not influence the behavioral olfactory threshold in mice.

scholarly journals The Ca2+-activated Cl− current ensures robust and reliable signal amplification in vertebrate olfactory receptor neurons

2018 ◽  
Author(s):  
Johannes Reisert ◽  
Jürgen Reingruber
Keyword(s):  
Olfactory Receptor ◽  
Signal Amplification ◽  
Olfactory Receptor Neuron ◽  
Olfactory Receptor Neurons ◽  
Ion Concentration ◽  
Modeling And Simulations ◽  
Small Space ◽  
Receptor Neurons ◽  
Concentration Changes ◽  
Transduction Current

AbstractActivation of most primary sensory neurons results in transduction currents that are carried by cations. One notable exception is the vertebrate olfactory receptor neuron (ORN), where the transduction current is carried largely by the anion Cl−. However, it remains unclear why ORNs use an anionic current for signal amplification. We have sought to provide clarification on this topic by studying the so far neglected dynamics of Na+, Ca2+, K+ and Cl− in the small space of olfactory cilia during an odorant response. Using computational modeling and simulations we compared the outcomes of signal amplification based on either Cl− or Na+ currents. We found that amplification produced by Na+ influx instead of a Cl− efflux is problematic due to several reasons: First, the Na+ current amplitude varies greatly depending on mucosal ion concentration changes. Second, a Na+ current leads to a large increase in the ciliary Na+ concentration during an odorant response. This increase inhibits and even reverses Ca2+ clearance by Na+/Ca2+/K+ exchange, which is essential for response termination. Finally, a Na+ current increases the ciliary osmotic pressure, which could cause swelling to damage the cilia. By contrast, a transduction pathway based on Cl− efflux circumvents these problems and renders the odorant response robust and reliable.

scholarly journals Ca2+-activated Cl current predominates in threshold response of mouse olfactory receptor neurons

2018 ◽  
Vol 115 (21) ◽  
pp. 5570-5575 ◽  
Author(s):  
Rong-Chang Li ◽  
Chih-Chun Lin ◽  
Xiaozhi Ren ◽  
Jingjing Sherry Wu ◽  
Laurie L. Molday ◽  
...  
Keyword(s):  
Olfactory Receptor ◽  
Signal Amplification ◽  
Olfactory Receptor Neurons ◽  
Behavioral Threshold ◽  
Olfactory Transduction ◽  
Threshold Response ◽  
Axonal Projections ◽  
Cl Channels ◽  
Receptor Neurons ◽  
The Brain

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 Ca2+ influx through open CNG channels triggers an inward current through Ca2+-activated Cl channels (ANO2), which is expected to produce signal amplification. However, a study on an Ano2−/− mouse line reported no elevation in the behavioral threshold of odorant detection compared with wild type (WT). Subsequent studies by others on the same Ano2−/− 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.

scholarly journals Signal Amplification in Drosophila Olfactory Receptor Neurons

Neuron ◽  
2019 ◽  
Vol 104 (5) ◽  
pp. 829-831
Author(s):  
Byoung Soo Kim ◽  
Greg S.B. Suh
Keyword(s):  
Olfactory Receptor ◽  
Signal Amplification ◽  
Olfactory Receptor Neurons ◽  
Receptor Neurons

scholarly journals Calcium-activated chloride channels clamp odor-evoked spike activity in olfactory receptor neurons

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Joseph D. Zak ◽  
Julien Grimaud ◽  
Rong-Chang Li ◽  
Chih-Chun Lin ◽  
Venkatesh N. Murthy
Keyword(s):  
Spike Activity ◽  
Olfactory Receptor ◽  
Chloride Channels ◽  
Olfactory Receptor Neurons ◽  
Receptor Neurons
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