Spontaneous and sensory-evoked activity in mouse olfactory sensory neurons with defined odorant receptors

Sensory systems need to tease out stimulation-evoked activity against a noisy background. In the olfactory system, the odor response profile of an olfactory sensory neuron (OSN) is dependent on the type of odorant receptor it expresses. OSNs also exhibit spontaneous activity, which plays a role in establishing proper synaptic connections and may also increase the sensitivity of the cells. However, where the spontaneous activity originates and whether it informs sensory-evoked activity remain unclear. We addressed these questions by examining patch-clamp recordings of genetically labeled mouse OSNs with defined odorant receptors in intact olfactory epithelia. We show that OSNs expressing different odorant receptors had significantly different rates of basal activity. Additionally, OSNs expressing an inactive mutant I7 receptor completely lacked spontaneous activity, despite being able to fire action potentials in response to current injection. This finding strongly suggests that the spontaneous firing of an OSN originates from the spontaneous activation of its G protein-coupled odorant receptor. Moreover, OSNs expressing the same receptor displayed considerable variation in their spontaneous activity, and the variation was broadened upon odor stimulation. Interestingly, there is no significant correlation between the spontaneous and sensory-evoked activity in these neurons. This study reveals that the odorant receptor type determines the spontaneous firing rate of OSNs, but the basal activity does not correlate with the activity induced by near-saturated odor stimulation. The implications of these findings on olfactory information processing are discussed.

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The cell biology of smell

The Journal of Cell Biology ◽

10.1083/jcb.201008163 ◽

2010 ◽

Vol 191 (3) ◽

pp. 443-452 ◽

Cited By ~ 90

Author(s):

Shannon DeMaria ◽

John Ngai

Keyword(s):

Olfactory System ◽

Cell Biology ◽

Odorant Receptor ◽

Large Family ◽

G Protein Coupled Receptors ◽

Odorant Receptors ◽

Chemical Structures ◽

Wide Range ◽

G Protein Coupled ◽

The Brain

The olfactory system detects and discriminates myriad chemical structures across a wide range of concentrations. To meet this task, the system utilizes a large family of G protein–coupled receptors—the odorant receptors—which are the chemical sensors underlying the perception of smell. Interestingly, the odorant receptors are also involved in a number of developmental decisions, including the regulation of their own expression and the patterning of the olfactory sensory neurons' synaptic connections in the brain. This review will focus on the diverse roles of the odorant receptor in the function and development of the olfactory system.

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Origin of basal activity in mammalian olfactory receptor neurons

The Journal of General Physiology ◽

10.1085/jgp.201010528 ◽

2010 ◽

Vol 136 (5) ◽

pp. 529-540 ◽

Cited By ~ 44

Author(s):

Johannes Reisert

Keyword(s):

Olfactory Receptor ◽

Information Transfer ◽

Odorant Receptor ◽

Olfactory Receptor Neurons ◽

Odorant Receptors ◽

Action Potential Firing ◽

Response Characteristics ◽

Basal Activity ◽

Receptor Neurons ◽

Different Response

Mammalian odorant receptors form a large, diverse group of G protein–coupled receptors that determine the sensitivity and response profile of olfactory receptor neurons. But little is known if odorant receptors control basal and also stimulus-induced cellular properties of olfactory receptor neurons other than ligand specificity. This study demonstrates that different odorant receptors have varying degrees of basal activity, which drives concomitant receptor current fluctuations and basal action potential firing. This basal activity can be suppressed by odorants functioning as inverse agonists. Furthermore, odorant-stimulated olfactory receptor neurons expressing different odorant receptors can have strikingly different response patterns in the later phases of prolonged stimulation. Thus, the influence of odorant receptor choice on response characteristics is much more complex than previously thought, which has important consequences on odor coding and odor information transfer to the brain.

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Spatiotemporal structure of sensory-evoked and spontaneous activity revealed by mesoscale imaging in anesthetized and awake mice

10.1101/2020.05.22.111021 ◽

2020 ◽

Cited By ~ 1

Author(s):

Navvab Afrashteh ◽

Samsoon Inayat ◽

Edgar Bermudez Contreras ◽

Artur Luczak ◽

Bruce L. McNaughton ◽

...

Keyword(s):

Spontaneous Activity ◽

Brain Activity ◽

Activity Patterns ◽

Sensory Stimulation ◽

Wide Field ◽

Evoked Responses ◽

Evoked Activity ◽

Cortical Regions ◽

The One ◽

Sensory Evoked

AbstractBrain activity propagates across the cortex in diverse spatiotemporal patterns, both as a response to sensory stimulation and during spontaneous activity. Despite been extensively studied, the relationship between the characteristics of such patterns during spontaneous and evoked activity is not completely understood. To investigate this relationship, we compared visual, auditory, and tactile evoked activity patterns elicited with different stimulus strengths and spontaneous activity motifs in lightly anesthetized and awake mice using mesoscale wide-field voltage-sensitive dye and glutamate imaging respectively. The characteristics of cortical activity that we compared include amplitude, speed, direction, and complexity of propagation trajectories in spontaneous and evoked activity patterns. We found that the complexity of the propagation trajectories of spontaneous activity, quantified as their fractal dimension, is higher than the one from sensory evoked responses. Moreover, the speed and direction of propagation, are modulated by the amplitude during both, spontaneous and evoked activity. Finally, we found that spontaneous activity had similar amplitude and speed when compared to evoked activity elicited with low stimulus strengths. However, this similarity gradually decreased when the strength of stimuli eliciting evoked responses increased. Altogether, these findings are consistent with the fact that even primary sensory areas receive widespread inputs from other cortical regions, and that, during rest, the cortex tends to reactivate traces of complex, multi-sensory experiences that may have occurred in a range of different behavioural contexts.

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Spontaneous Afferent Activity Carves Olfactory Circuits

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2021.637536 ◽

2021 ◽

Vol 15 ◽

Author(s):

Nelly Redolfi ◽

Claudia Lodovichi

Keyword(s):

Electrical Activity ◽

Brain Function ◽

Odorant Receptors ◽

Spontaneous Discharge ◽

Normal Brain ◽

Sensory Modalities ◽

Normal Brain Function ◽

Evoked Activity ◽

Sensory Evoked

Electrical activity has a key role in shaping neuronal circuits during development. In most sensory modalities, early in development, internally generated spontaneous activity sculpts the initial layout of neuronal wiring. With the maturation of the sense organs, the system relies more on sensory-evoked electrical activity. Stimuli-driven neuronal discharge is required for the transformation of immature circuits in the specific patterns of neuronal connectivity that subserve normal brain function. The olfactory system (OS) differs from this organizational plan. Despite the important role of odorant receptors (ORs) in shaping olfactory topography, odor-evoked activity does not have a prominent role in refining neuronal wiring. On the contrary, afferent spontaneous discharge is required to achieve and maintain the specific diagram of connectivity that defines the topography of the olfactory bulb (OB). Here, we provide an overview of the development of olfactory topography, with a focus on the role of afferent spontaneous discharge in the formation and maintenance of the specific synaptic contacts that result in the topographic organization of the OB.

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The macrophage odorant receptor Olfr78 mediates the lactate-induced M2 phenotype of tumor-associated macrophages

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2102434118 ◽

2021 ◽

Vol 118 (37) ◽

pp. e2102434118

Author(s):

Sri Murugan Poongkavithai Vadevoo ◽

Gowri Rangaswamy Gunassekaran ◽

ChaeEun Lee ◽

NaHye Lee ◽

Jiyoun Lee ◽

...

Keyword(s):

Tumor Progression ◽

Immune Cell ◽

Odorant Receptor ◽

Odorant Receptors ◽

Tumor Associated Macrophages ◽

Immune Cell Population ◽

Lactate Sensor ◽

And Function ◽

Multiple Signaling ◽

G Protein Coupled

Expression and function of odorant receptors (ORs), which account for more than 50% of G protein–coupled receptors, are being increasingly reported in nonolfactory sites. However, ORs that can be targeted by drugs to treat diseases remain poorly identified. Tumor-derived lactate plays a crucial role in multiple signaling pathways leading to generation of tumor-associated macrophages (TAMs). In this study, we hypothesized that the macrophage OR Olfr78 functions as a lactate sensor and shapes the macrophage–tumor axis. Using Olfr78+/+ and Olfr78−/− bone marrow–derived macrophages with or without exogenous Olfr78 expression, we demonstrated that Olfr78 sensed tumor-derived lactate, which was the main factor in tumor-conditioned media responsible for generation of protumoral M2-TAMs. Olfr78 functioned together with Gpr132 to mediate lactate-induced generation of protumoral M2-TAMs. In addition, syngeneic Olfr78-deficient mice exhibited reduced tumor progression and metastasis together with an increased anti- versus protumoral immune cell population. We propose that the Olfr78–lactate interaction is a therapeutic target to reduce and prevent tumor progression and metastasis.

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Responsiveness of G protein-coupled odorant receptors is partially attributed to the activation mechanism

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1517510112 ◽

2015 ◽

Vol 112 (48) ◽

pp. 14966-14971 ◽

Cited By ~ 30

Author(s):

Yiqun Yu ◽

Claire A. de March ◽

Mengjue J. Ni ◽

Kaylin A. Adipietro ◽

Jérôme Golebiowski ◽

...

Keyword(s):

G Protein ◽

Receptor Activation ◽

Site Directed Mutagenesis ◽

Activation Mechanism ◽

Odorant Receptors ◽

Structural Basis ◽

Single Mutation ◽

Response Properties ◽

Basal Activity ◽

G Protein Coupled

Mammals detect and discriminate numerous odors via a large family of G protein-coupled odorant receptors (ORs). However, little is known about the molecular and structural basis underlying OR response properties. Using site-directed mutagenesis and computational modeling, we studied ORs sharing high sequence homology but with different response properties. When tested in heterologous cells by diverse odorants, MOR256-3 responded broadly to many odorants, whereas MOR256-8 responded weakly to a few odorants. Out of 36 mutant MOR256-3 ORs, the majority altered the responses to different odorants in a similar manner and the overall response of an OR was positively correlated with its basal activity, an indication of ligand-independent receptor activation. Strikingly, a single mutation in MOR256-8 was sufficient to confer both high basal activity and broad responsiveness to this receptor. These results suggest that broad responsiveness of an OR is at least partially attributed to its activation likelihood.

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The assembled and annotated genome of the pigeon louse Columbicola columbae, a model ectoparasite

G3 Genes|Genome|Genetics ◽

10.1093/g3journal/jkab009 ◽

2021 ◽

Vol 11 (2) ◽

Author(s):

James G Baldwin-Brown ◽

Scott M Villa ◽

Anna I Vickrey ◽

Kevin P Johnson ◽

Sarah E Bush ◽

...

Keyword(s):

Low Cost ◽

Single Copy ◽

Odorant Receptors ◽

Rna Seq ◽

Pediculus Humanus ◽

Final Assembly ◽

Oxford Nanopore ◽

Genes Encoding ◽

Host Parasite ◽

G Protein Coupled

Abstract The pigeon louse Columbicola columbae is a longstanding and important model for studies of ectoparasitism and host-parasite coevolution. However, a deeper understanding of its evolution and capacity for rapid adaptation is limited by a lack of genomic resources. Here, we present a high-quality draft assembly of the C. columbae genome, produced using a combination of Oxford Nanopore, Illumina, and Hi-C technologies. The final assembly is 208 Mb in length, with 12 chromosome-size scaffolds representing 98.1% of the assembly. For gene model prediction, we used a novel clustering method (wavy_choose) for Oxford Nanopore RNA-seq reads to feed into the MAKER annotation pipeline. High recovery of conserved single-copy orthologs (BUSCOs) suggests that our assembly and annotation are both highly complete and highly accurate. Consistent with the results of the only other assembled louse genome, Pediculus humanus, we find that C. columbae has a relatively low density of repetitive elements, the majority of which are DNA transposons. Also similar to P. humanus, we find a reduced number of genes encoding opsins, G protein-coupled receptors, odorant receptors, insulin signaling pathway components, and detoxification proteins in the C. columbae genome, relative to other insects. We propose that such losses might characterize the genomes of obligate, permanent ectoparasites with predictable habitats, limited foraging complexity, and simple dietary regimes. The sequencing and analysis for this genome were relatively low cost, and took advantage of a new clustering technique for Oxford Nanopore RNAseq reads that will be useful to future genome projects.

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G protein-coupled odorant receptors underlie mechanosensitivity in mammalian olfactory sensory neurons

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1418515112 ◽

2014 ◽

Vol 112 (2) ◽

pp. 590-595 ◽

Cited By ~ 43

Author(s):

Timothy Connelly ◽

Yiqun Yu ◽

Xavier Grosmaitre ◽

Jue Wang ◽

Lindsey C. Santarelli ◽

...

Keyword(s):

G Protein ◽

Sensory Neurons ◽

Ectopic Expression ◽

Host Cells ◽

Odorant Receptors ◽

Olfactory Sensory Neurons ◽

Mechanical Stimuli ◽

Genetic Ablation ◽

Mechanical Responses ◽

G Protein Coupled

Mechanosensitive cells are essential for organisms to sense the external and internal environments, and a variety of molecules have been implicated as mechanical sensors. Here we report that odorant receptors (ORs), a large family of G protein-coupled receptors, underlie the responses to both chemical and mechanical stimuli in mouse olfactory sensory neurons (OSNs). Genetic ablation of key signaling proteins in odor transduction or disruption of OR–G protein coupling eliminates mechanical responses. Curiously, OSNs expressing different OR types display significantly different responses to mechanical stimuli. Genetic swap of putatively mechanosensitive ORs abolishes or reduces mechanical responses of OSNs. Furthermore, ectopic expression of an OR restores mechanosensitivity in loss-of-function OSNs. Lastly, heterologous expression of an OR confers mechanosensitivity to its host cells. These results indicate that certain ORs are both necessary and sufficient to cause mechanical responses, revealing a previously unidentified mechanism for mechanotransduction.

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