scholarly journals Odor sampling strategies in mice with genetically altered olfactory responses

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0249798
Author(s):  
Johannes Reisert ◽  
Glen J. Golden ◽  
Michele Dibattista ◽  
Alan Gelperin
Keyword(s):  
Knockout Mice ◽  
Olfactory Receptor ◽  
Environmental Changes ◽  
Dynamic Range ◽  
Olfactory Receptor Neuron ◽  
Olfactory Receptor Neurons ◽  
Receptor Neuron ◽  
Sensory Cells ◽  
Receptor Neurons ◽  
Kinetics Of

Peripheral sensory cells and the central neuronal circuits that monitor environmental changes to drive behaviors should be adapted to match the behaviorally relevant kinetics of incoming stimuli, be it the detection of sound frequencies, the speed of moving objects or local temperature changes. Detection of odorants begins with the activation of olfactory receptor neurons in the nasal cavity following inhalation of air and airborne odorants carried therein. Thus, olfactory receptor neurons are stimulated in a rhythmic and repeated fashion that is determined by the breathing or sniffing frequency that can be controlled and altered by the animal. This raises the question of how the response kinetics of olfactory receptor neurons are matched to the imposed stimulation frequency and if, vice versa, the kinetics of olfactory receptor neuron responses determine the sniffing frequency. We addressed this question by using a mouse model that lacks the K+-dependent Na+/Ca2+ exchanger 4 (NCKX4), which results in markedly slowed response termination of olfactory receptor neuron responses and hence changes the temporal response kinetics of these neurons. We monitored sniffing behaviors of freely moving wildtype and NCKX4 knockout mice while they performed olfactory Go/NoGo discrimination tasks. Knockout mice performed with similar or, surprisingly, better accuracy compared to wildtype mice, but chose, depending on the task, different odorant sampling durations depending on the behavioral demands of the odorant identification task. Similarly, depending on the demands of the behavioral task, knockout mice displayed a lower basal breathing frequency prior to odorant sampling, a possible mechanism to increase the dynamic range for changes in sniffing frequency during odorant sampling. Overall, changes in sniffing behavior between wildtype and NCKX4 knockout mice were subtle, suggesting that, at least for the particular odorant-driven task we used, slowed response termination of the odorant-induced receptor neuron response either has a limited detrimental effect on odorant-driven behavior or mice are able to compensate via an as yet unknown mechanism.

Functional properties of vertebrate olfactory receptor neurons

1986 ◽  
Vol 66 (3) ◽  
pp. 772-818 ◽  
Author(s):  
T. V. Getchell
Keyword(s):  
Olfactory Receptor ◽  
Olfactory Receptor Neuron ◽  
Olfactory Nerve ◽  
Sensory Transduction ◽  
Olfactory Receptor Neurons ◽  
Receptor Neuron ◽  
Olfactory Pathway ◽  
Receptor Neurons ◽  
Molecular Biological Techniques

The interaction of an odorant with the chemosensitive membrane of olfactory receptor neurons initiates a sequence of molecular and membrane events leading to sensory transduction, impulse initiation, and the transmission of sensory information to the brain. The main steps in this sequence are summarized in Figure 6. Several lines of evidence support the hypothesis that the initial molecular events and subsequent stages of transduction are mediated by odorant receptor sites and associated ion channels located in the membrane of the cilia and apical dendritic knob of the olfactory receptor neuron. Similarly, the membrane events associated with impulse initiation and propagation are mediated by voltage-gated channels located in the initial axonal segment and the axolemma. The ionic and electrical events associated with the proposed sequence have been characterized in general using a variety of experimental techniques. The identification, localization, and sequence of membrane events are consistent with the neurophysiological properties observed in specific regions of the bipolar receptor neuron. The influence of other cells in the primary olfactory pathway such as the sustentacular cells in the olfactory epithelium, the Schwann cells in the olfactory nerve, and the astrocytes in the olfactory nerve layer in the olfactory bulb on the physiological activity of the olfactory receptor neuron is an emerging area of research interests. The general principles derived from the experimental results described in this review provide only a framework that is both incomplete and of necessity somewhat speculative. As noted in the Introduction, the multidisciplinary study of the primary olfactory pathway is undergoing a renaissance of research interest. The application of modern biophysical, cell, and molecular biological techniques to the basic issues of odorant recognition and membrane excitability will clarify the speculations and lead to the establishment of new hypotheses. Three broad areas of research will benefit from such studies. First, the application of biophysical techniques will lead to a detailed characterization of the membrane properties and associated ion conductance mechanisms. Second, the isolation and biochemical characterization of intrinsic membrane and cytosolic proteins associated with odorant recognition, sensory transduction, and the subsequent electrical events will result from the utilization of cell and molecular biological techniques.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Adaptive integrate-and-fire model reproduces the dynamics of olfactory receptor neuron responses in a moth

2019 ◽  
Vol 16 (157) ◽  
pp. 20190246 ◽  
Author(s):  
Marie Levakova ◽  
Lubomir Kostal ◽  
Christelle Monsempès ◽  
Philippe Lucas ◽  
Ryota Kobayashi
Keyword(s):  
Olfactory Receptor ◽  
Time Course ◽  
Olfactory Receptor Neuron ◽  
Receptor Activation ◽  
Olfactory Receptor Neurons ◽  
Response Dynamics ◽  
Spike Threshold ◽  
Olfactory Stimuli ◽  
Receptor Neurons ◽  
The Brain

In order to understand how olfactory stimuli are encoded and processed in the brain, it is important to build a computational model for olfactory receptor neurons (ORNs). Here, we present a simple and reliable mathematical model of a moth ORN generating spikes. The model incorporates a simplified description of the chemical kinetics leading to olfactory receptor activation and action potential generation. We show that an adaptive spike threshold regulated by prior spike history is an effective mechanism for reproducing the typical phasic–tonic time course of ORN responses. Our model reproduces the response dynamics of individual neurons to a fluctuating stimulus that approximates odorant fluctuations in nature. The parameters of the spike threshold are essential for reproducing the response heterogeneity in ORNs. The model provides a valuable tool for efficient simulations of olfactory circuits.

scholarly journals Inhibitory Odorant Signaling in Mammalian Olfactory Receptor Neurons

2010 ◽  
Vol 103 (2) ◽  
pp. 1114-1122 ◽  
Author(s):  
Kirill Ukhanov ◽  
Elizabeth A. Corey ◽  
Daniela Brunert ◽  
Katharina Klasen ◽  
Barry W. Ache
Keyword(s):  
Olfactory Receptor ◽  
Olfactory Receptor Neurons ◽  
Electrophysiological Response ◽  
Cellular Processes ◽  
Receptor Neurons ◽  
Phosphoinositide 3 Kinase ◽  
Mixture Suppression ◽  
G Protein Coupled ◽  
Kinetics Of

Odorants inhibit as well as excite olfactory receptor neurons (ORNs) in many species of animals. Cyclic nucleotide-dependent activation of canonical mammalian ORNs is well established but it is still unclear how odorants inhibit these cells. Here we further implicate phosphoinositide-3-kinase (PI3K), an indispensable element of PI signaling in many cellular processes, in olfactory transduction in rodent ORNs. We show that odorants rapidly and transiently activate PI3K in the olfactory cilia and in the olfactory epithelium in vitro. We implicate known G-protein–coupled isoforms of PI3K and show that they modulate not only the magnitude but also the onset kinetics of the electrophysiological response of ORNs to complex odorants. Finally, we show that the ability of a single odorant to inhibit another can be PI3K dependent. Our collective results provide compelling support for the idea that PI3K-dependent signaling mediates inhibitory odorant input to mammalian ORNs and at least in part contributes to the mixture suppression typically seen in the response of ORNs to complex natural odorants.

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 Effects of Odor Stimulation on Antidromic Spikes in Olfactory Sensory Neurons

2008 ◽  
Vol 100 (6) ◽  
pp. 3074-3085 ◽  
Author(s):  
John W. Scott ◽  
Lisa Sherrill
Keyword(s):  
Electrical Stimulation ◽  
Sensory Neurons ◽  
Olfactory Receptor ◽  
Olfactory Receptor Neuron ◽  
Olfactory Nerve ◽  
Receptor Neuron ◽  
Odor Stimulus ◽  
Olfactory Sensory Neurons ◽  
Strongly Correlated ◽  
Receptor Neurons

Spikes were evoked in rat olfactory sensory neuron (OSN) populations by electrical stimulation of the olfactory bulb nerve layer in pentobarbital anesthetized rats. The latencies and recording positions for these compound spikes showed that they originated in olfactory epithelium. Dual simultaneous recordings indicated conduction velocities in the C-fiber range, around 0.5 m/s. These spikes are concluded to arise from antidromically activated olfactory sensory neurons. Electrical stimulation at 5 Hz was used to track changes in the size and latency of the antidromic compound population spike during the odor response. Strong odorant stimuli suppressed the spike size and prolonged its latency. The latency was prolonged throughout long odor stimuli, indicating continued activation of olfactory receptor neuron axons. The amounts of spike suppression and latency change were strongly correlated with the electroolfactogram (EOG) peak size evoked at the same site across odorants and across stimulus intensities. We conclude that the curve of antidromic spike suppression gives a reasonable representation of spiking activity in olfactory sensory neurons driven by odorants and that the correlation of peak spike suppression with the peak EOG shows the accuracy of the EOG as an estimate of intracellular potential in the population of olfactory sensory neurons. In addition, these results have important implications about traffic in olfactory nerve bundles. We did not observe multiple peaks corresponding to stimulated and unstimulated receptor neurons. This suggests synchronization of spikes in olfactory nerve, perhaps by ephaptic interactions. The long-lasting effect on spike latency shows that action potentials continue in the nerve throughout the duration of an odor stimulus in spite of many reports of depolarization block in olfactory receptor neuron cell bodies. Finally, strong odor stimulation caused almost complete block of antidromic spikes. This indicates that a very large proportion of olfactory axons was activated by single strong odor stimuli.

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 Multi-glomerular projection of single olfactory receptor neurons is conserved among amphibians

2019 ◽  
Author(s):  
Lukas Weiss ◽  
Lucas D. Jungblut ◽  
Andrea G. Pozzi ◽  
Barbara S. Zielinski ◽  
Lauren A. O’Connell ◽  
...  
Keyword(s):  
Olfactory Receptor ◽  
Olfactory Receptor Neuron ◽  
Receptor Neuron ◽  
Projection Neurons ◽  
Amphibian Species ◽  
Odor Processing ◽  
Axonal Projections ◽  
Frog Species ◽  
Receptor Neurons ◽  
Jawless Fish

Individual receptor neurons in the peripheral olfactory organ extend long axons into the olfactory bulb forming synapses with projection neurons in spherical neuropil regions, called glomeruli. Generally, odor map formation and odor processing in all vertebrates is based on the assumption that receptor neuron axons exclusively connect to a single glomerulus without any axonal branching. We comparatively tested this hypothesis in multiple fish and amphibian species by applying sparse cell electroporation to trace single olfactory receptor neuron axons. Sea lamprey (jawless fish) and zebrafish (bony fish) support the unbranched axon concept, with 94% of axons terminating in single glomeruli. Contrastingly, axonal projections of the axolotl (salamander) branch extensively before entering up to six distinct glomeruli. Receptor neuron axons labeled in frog species (Pipidae, Bufonidae, Hylidae and Dendrobatidae) predominantly bifurcate before entering a glomerulus and 59% and 50% connect to multiple glomeruli in larval and post-metamorphotic animals, respectively. Independent of developmental stage, lifestyle and adaptations to specific habitats, it seems to be a common feature of amphibian olfactory receptor neuron axons to frequently bifurcate and connect to multiple glomeruli. Our study challenges the unbranched axon concept as a universal vertebrate feature and it is conceivable that also later diverging vertebrates deviate from it. We propose that this unusual wiring logic evolved around the divergence of the terrestrial tetrapod lineage from its aquatic ancestors and could be the basis of an alternative way of odor processing.Abstract Figure

scholarly journals Non-synaptic interactions between olfactory receptor neurons, a possible key feature of odor processing in flies

2021 ◽  
Vol 17 (12) ◽  
pp. e1009583
Author(s):  
Mario Pannunzi ◽  
Thomas Nowotny
Keyword(s):  
Lateral Inhibition ◽  
Olfactory Receptor ◽  
Antennal Lobe ◽  
Dynamic Range ◽  
Olfactory Receptor Neurons ◽  
Alternative Mechanism ◽  
Mixture Ratio ◽  
Odor Processing ◽  
Functional Perspective ◽  
Receptor Neurons

When flies explore their environment, they encounter odors in complex, highly intermittent plumes. To navigate a plume and, for example, find food, they must solve several challenges, including reliably identifying mixtures of odorants and their intensities, and discriminating odorant mixtures emanating from a single source from odorants emitted from separate sources and just mixing in the air. Lateral inhibition in the antennal lobe is commonly understood to help solving these challenges. With a computational model of the Drosophila olfactory system, we analyze the utility of an alternative mechanism for solving them: Non-synaptic (“ephaptic”) interactions (NSIs) between olfactory receptor neurons that are stereotypically co-housed in the same sensilla. We find that NSIs improve mixture ratio detection and plume structure sensing and do so more efficiently than the traditionally considered mechanism of lateral inhibition in the antennal lobe. The best performance is achieved when both mechanisms work in synergy. However, we also found that NSIs decrease the dynamic range of co-housed ORNs, especially when they have similar sensitivity to an odorant. These results shed light, from a functional perspective, on the role of NSIs, which are normally avoided between neurons, for instance by myelination.

scholarly journals Combinations of DIPs and Dprs control organization of olfactory receptor neuron terminals in Drosophila

2018 ◽  
Author(s):  
Scott Barish ◽  
Sarah Nuss ◽  
Ilya Strunilin ◽  
Suyang Bao ◽  
Sayan Mukherjee ◽  
...  
Keyword(s):  
Axon Guidance ◽  
Olfactory Receptor ◽  
Antennal Lobe ◽  
Olfactory Receptor Neuron ◽  
Olfactory Receptor Neurons ◽  
Surface Receptors ◽  
Differential Adhesion ◽  
Receptor Neurons ◽  
Neuron Terminals ◽  
Cell Adhesion Proteins

SummaryIn Drosophila, 50 classes of olfactory receptor neurons (ORNs) connect to 50 class-specific and uniquely positioned glomeruli in the antennal lobe. Despite the identification of cell surface receptors regulating axon guidance, how ORN axons sort to form 50 stereotypical glomeruli remains unclear. Here we show that the heterophilic cell adhesion proteins, DIPs and Dprs, are expressed in ORNs during glomerular formation. Each ORN class expresses a unique combination of DIPs/dprs, with neurons of the same class expressing interacting partners, suggesting a role in class-specific self-adhesion ORN axons. Analysis of DIP/Dpr expression revealed that ORNS that target neighboring glomeruli have different combinations, and ORNs with very similar DIP/Dpr combinations can project to distant glomeruli in the antennal lobe. Perturbations of DIP/dpr gene function result in local projection defects of ORN axons and glomerular positioning, without altering correct matching of ORNs with their target neurons. Our results suggest that context-dependent differential adhesion through DIP/Dpr combinations regulate self-adhesion and sort ORN axons into uniquely positioned glomeruli.

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