Signal Transduction in Vertebrate Olfactory Receptor Cells

The Journal of Physiology

2011

Non-technical summary Odorants are transported into the nasal cavity upon air inhalation where they are detected by olfactory receptor neurons (ORNs), which transduce the odorant molecules into action potentials. The rate of stimulation thus depends on the chosen breathing frequency, which in mice ranges from 2 to 10 Hz. This poses the question how ORNs respond to rapidly changing stimulation rates. Individual mouse ORNs respond reliably to repetitive 2 Hz stimulations resembling normal breathing, but actually perform much poorer when the stimulation rate is increased to 5 Hz, which is more akin to sniffing. In this case, rarely more than 50% of the stimulations elicit any response, with an increase in odorant concentration further reducing the response rate, becoming zero at high concentrations. This counterintuitive observation can be understood in the framework of an adaptive filter, which allows the animal to selectively alter its ORN output depending on the chosen breathing rate.Abstract Vertebrate olfactory receptor neurons (ORNs) are stimulated in a rhythmic manner in vivo, driven by delivery of odorants to the nasal cavity carried by the inhaled air, making olfaction a sense where animals can control the frequency of stimulus delivery. How ORNs encode repeated stimulation at resting, low breathing frequencies and at increased sniffing frequencies is not known, nor is it known if the olfactory transduction cascade is accurate and fast enough to follow high frequency stimulation. We investigated mouse olfactory responses to stimulus frequencies mimicking odorant exposure during low (2 Hz) and high (5 Hz) frequency sniffing. ORNs reliably follow low frequency stimulations with high fidelity by generating bursts of action potentials at each stimulation at intermediate odorant concentrations, but fail to do so at high odorant concentrations. Higher stimulus frequencies across all odorant concentrations reduced the likelihood of action potential generation, increased the latency of response, and decreased the reliability of encoding the onset of stimulation. Thus an increase in stimulus frequency degrades and at high odorant concentrations entirely prevents action potential generation in individual ORNs, causing reduced signalling to the olfactory bulb. These results demonstrate that ORNs do not simply relay timing and concentration of an odorous stimulus, but also process and modulate the stimulus in a frequency-dependent manner which is controlled by the chosen sniffing rate.

Section: Resultsmentioning

confidence: 99%

Olfactory receptor neuron responses coding for rapid odour sampling

Ghatpande

The Journal of Physiology

2011

“…The initial steps in the signal transduction pathway occur in long and slender cilia, for reviews see [22,1,42]. The activation of an odorant receptor in the ciliary membrane initiates a G proteincoupled cascade that leads to the opening of CNG channels.…”

Section: A Derivation Of the Spatially Resolved Modelmentioning

confidence: 99%

“…It is still unclear why ORNs rely upon a Cl − current to boost the amplitude of their signal [20,21]. A larger signal could be produced if ORNs had more CNG channels, but a simple increase in channel number would produce larger influx of both N a + and Ca 2+ , which would disturb Ca 2+ homoeostasis and affect several Ca 2+ dependent feedback processes in the biochemical transduction pathway [1,22]. Moreover, a cilium has as volume of only about 0.5 femtoliter, and a current of just 1 pA already produces an ion flux of about 20 mM per second.…”

Section: Introductionmentioning

confidence: 99%

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

Reingruber

2018

Preprint

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 N a + , Ca 2+ , 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 N a + currents. We found that amplification produced by N a + influx instead of a Cl − efflux is problematic due to several reasons: First, the N a + current amplitude varies greatly depending on mucosal ion concentration changes. Second, a N a + current leads to a large increase in the ciliary N a + concentration during an odorant response. This increase inhibits and even reverses Ca 2+ clearance by N a + /Ca 2+ /K + exchange, which is essential for response termination. Finally, a N a + 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.

“…It is still unclear why ORNs rely upon a Cl − current to boost the amplitude of their response (21,22). A larger signal could be produced if ORNs had more CNG channels, but a simple increase in channel number would produce larger influx of both Na + and Ca 2+ , which would disturb Ca 2+ homeostasis and affect several Ca 2+ -dependent feedback processes in the biochemical transduction pathway (1,23). We note that a cilium has a volume of only about 0.5 fL, and a current of just 1 pA already produces an ion flux of about 20 mM/s.…”

mentioning

confidence: 99%

Ca ²⁺ -activated Cl ⁻ current ensures robust and reliable signal amplification in vertebrate olfactory receptor neurons

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

Reingruber

2018

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.