Semiochemical responsive olfactory sensory neurons are sexually dimorphic and plastic

Understanding how genes and experience work in concert to generate phenotypic variability will provide a better understanding of individuality. Here, we considered this in the main olfactory epithelium, a chemosensory structure with over a thousand distinct cell types in mice. We identified a subpopulation of olfactory sensory neurons, defined by receptor expression, whose abundances were sexually dimorphic. This subpopulation of olfactory sensory neurons was over-represented in sex-separated mice and robustly responsive to sex-specific semiochemicals. Sex-combined housing led to an attenuation of the dimorphic representations. Single-cell sequencing analysis revealed an axis of activity-dependent gene expression amongst a subset of the dimorphic OSN populations. Finally, the pro-apoptotic gene Baxwas necessary to generate the dimorphic representations. Altogether, our results suggest a role of experience and activity in influencing homeostatic mechanisms to generate a robust sexually dimorphic phenotype in the main olfactory epithelium.

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Semiochemical responsive olfactory sensory neurons are sexually dimorphic and plastic

10.1101/867044 ◽

2019 ◽

Author(s):

Aashutosh Vihani ◽

Xiaoyang Serene Hu ◽

Sivaji Gundala ◽

Sachiko Koyama ◽

Eric Block ◽

...

Keyword(s):

Sensory Neurons ◽

Olfactory Epithelium ◽

Phenotypic Variability ◽

Cell Types ◽

Receptor Expression ◽

Olfactory Sensory Neurons ◽

Sexually Dimorphic ◽

Main Olfactory Epithelium ◽

Distinct Cell ◽

Male Specific

AbstractUnderstanding how genes and experiences work in concert to generate phenotypic variability will provide a better understanding of individuality. Here, we considered this in the context of the main olfactory epithelium, a chemosensory structure with over a thousand distinct cell-types, in mice. We identified a subpopulation of at least three types of olfactory sensory neurons, defined by receptor expression, whose abundances were sexually dimorphic. This subpopulation of olfactory sensory neurons was over-represented in sex-separated female mice and responded robustly to the male-specific semiochemicals 2-sec-butyl-4,5-dihydrothaizole and (methylthio)methanethiol. Sex-combined housing led to a robust attenuation of the female over-representation. Testing of Bax null mice revealed a Bax-dependence in generating the sexual dimorphism in sex-separated mice. Altogether, our results suggest a profound role of experience in influencing homeostatic neural lifespan mechanisms to generate a robust sexually dimorphic phenotype in the main olfactory epithelium.

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Renewal and Differentiation of GCD Necklace Olfactory Sensory Neurons

Chemical Senses ◽

10.1093/chemse/bjaa027 ◽

2020 ◽

Vol 45 (5) ◽

pp. 333-346 ◽

Cited By ~ 1

Author(s):

Maria Lissitsyna Bloom ◽

Lucille B Johnston ◽

Sandeep Robert Datta

Keyword(s):

Sensory Neurons ◽

Olfactory Epithelium ◽

Developmental Trajectory ◽

Olfactory Sensory Neurons ◽

Differentiation Process ◽

Main Olfactory Epithelium ◽

Horizontal Migration ◽

Sensory Responses ◽

And Migration ◽

Β Tubulin

Abstract Both canonical olfactory sensory neurons (OSNs) and sensory neurons belonging to the guanylate cyclase D (GCD) “necklace” subsystem are housed in the main olfactory epithelium, which is continuously bombarded by toxins, pathogens, and debris from the outside world. Canonical OSNs address this challenge, in part, by undergoing renewal through neurogenesis; however, it is not clear whether GCD OSNs also continuously regenerate and, if so, whether newborn GCD precursors follow a similar developmental trajectory to that taken by canonical OSNs. Here, we demonstrate that GCD OSNs are born throughout adulthood and can persist in the epithelium for several months. Phosphodiesterase 2A is upregulated early in the differentiation process, followed by the sequential downregulation of β-tubulin and the upregulation of CART protein. The GCD and MS4A receptors that confer sensory responses upon GCD neurons are initially expressed midway through this process but become most highly expressed once CART levels are maximal late in GCD OSN development. GCD OSN maturation is accompanied by a horizontal migration of neurons toward the central, curved portions of the cul-de-sac regions where necklace cells are concentrated. These findings demonstrate that—like their canonical counterparts—GCD OSNs undergo continuous renewal and define a GCD-specific developmental trajectory linking neurogenesis, maturation, and migration.

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Cholinergic microvillous cells in the mouse main olfactory epithelium and effect of acetylcholine on olfactory sensory neurons and supporting cells

Journal of Neurophysiology ◽

10.1152/jn.00186.2011 ◽

2011 ◽

Vol 106 (3) ◽

pp. 1274-1287 ◽

Cited By ~ 44

Author(s):

Tatsuya Ogura ◽

Steven A. Szebenyi ◽

Kurt Krosnowski ◽

Aaron Sathyanesan ◽

Jacqueline Jackson ◽

...

Keyword(s):

Sensory Neurons ◽

Olfactory Epithelium ◽

Transient Receptor Potential ◽

Olfactory Sensory Neurons ◽

Dependent Manner ◽

Basal Cells ◽

Supporting Cells ◽

Concentration Dependent Manner ◽

External Stimulation ◽

Main Olfactory Epithelium

The mammalian olfactory epithelium is made up of ciliated olfactory sensory neurons (OSNs), supporting cells, basal cells, and microvillous cells. Previously, we reported that a population of nonneuronal microvillous cells expresses transient receptor potential channel M5 (TRPM5). Using transgenic mice and immunocytochemical labeling, we identify that these cells are cholinergic, expressing the signature markers of choline acetyltransferase (ChAT) and the vesicular acetylcholine transporter. This result suggests that acetylcholine (ACh) can be synthesized and released locally to modulate activities of neighboring supporting cells and OSNs. In Ca2+ imaging experiments, ACh induced increases in intracellular Ca2+ levels in 78% of isolated supporting cells tested in a concentration-dependent manner. Atropine, a muscarinic ACh receptor (mAChR) antagonist suppressed the ACh responses. In contrast, ACh did not induce or potentiate Ca2+ increases in OSNs. Instead ACh suppressed the Ca2+ increases induced by the adenylyl cyclase activator forskolin in some OSNs. Supporting these results, we found differential expression of mAChR subtypes in supporting cells and OSNs using subtype-specific antibodies against M1 through M5 mAChRs. Furthermore, we found that various chemicals, bacterial lysate, and cold saline induced Ca2+ increases in TRPM5/ChAT-expressing microvillous cells. Taken together, our data suggest that TRPM5/ChAT-expressing microvillous cells react to certain chemical or thermal stimuli and release ACh to modulate activities of neighboring supporting cells and OSNs via mAChRs. Our studies reveal an intrinsic and potentially potent mechanism linking external stimulation to cholinergic modulation of activities in the olfactory epithelium.

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Connectivity from OR37 expressing olfactory sensory neurons to distinct cell types in the hypothalamus

Frontiers in Neural Circuits ◽

10.3389/fncir.2012.00084 ◽

2012 ◽

Vol 6 ◽

Cited By ~ 26

Author(s):

Andrea Bader ◽

Bettina Klein ◽

Heinz Breer ◽

Jörg Strotmann

Keyword(s):

Sensory Neurons ◽

Cell Types ◽

Olfactory Sensory Neurons ◽

Distinct Cell

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Development of the main olfactory system and main olfactory epithelium-dependent male mating behavior are altered in Go-deficient mice

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1613026113 ◽

2016 ◽

Vol 113 (39) ◽

pp. 10974-10979 ◽

Cited By ~ 10

Author(s):

Jung-Mi Choi ◽

Sung-Soo Kim ◽

Chan-Il Choi ◽

Hye Lim Cha ◽

Huy-Hyen Oh ◽

...

Keyword(s):

Mating Behavior ◽

Sensory Neurons ◽

Olfactory Epithelium ◽

Sexual Behaviors ◽

Cell Types ◽

Mutant Mice ◽

Male Mating ◽

Α Subunit ◽

Female Mice ◽

Main Olfactory Epithelium

In mammals, initial detection of olfactory stimuli is mediated by sensory neurons in the main olfactory epithelium (MOE) and the vomeronasal organ (VNO). The heterotrimeric GTP-binding protein Go is widely expressed in the MOE and VNO of mice. Early studies indicated that Go expression in VNO sensory neurons is critical for directing social and sexual behaviors in female mice [Oboti L, et al. (2014) BMC Biol 12:31]. However, the physiological functions of Go in the MOE have remained poorly defined. Here, we examined the role of Go in the MOE using mice lacking the α subunit of Go. Development of the olfactory bulb (OB) was perturbed in mutant mice as a result of reduced neurogenesis and increased cell death. The balance between cell types of OB interneurons was altered in mutant mice, with an increase in the number of tyrosine hydroxylase-positive interneurons at the expense of calbindin-positive interneurons. Sexual behavior toward female mice and preference for female urine odors by olfactory sensory neurons in the MOE were abolished in mutant male mice. Our data suggest that Go signaling is essential for the structural and functional integrity of the MOE and for specification of OB interneurons, which in turn are required for the transmission of pheromone signals and the initiation of mating behavior with the opposite sex.

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microRNA-252 and FoxO repress inflammaging by a dual inhibitory mechanism on Dawdle mediated TGF-β pathway in Drosophila

Genetics ◽

10.1093/genetics/iyab234 ◽

2021 ◽

Author(s):

Xiaofen Wu ◽

Kongyan Niu ◽

Xiaofan Wang ◽

Jing Zhao ◽

Han Wang ◽

...

Keyword(s):

Cell Types ◽

Innate Immune ◽

Low Grade ◽

Sequencing Analysis ◽

Immune Genes ◽

Healthy Longevity ◽

Muscle Tissues ◽

Distinct Cell ◽

A Cell ◽

Innate Immune Genes

Abstract Inflammaging refers to low-grade, chronically activated innate immunity that has deleterious effects on healthy lifespan. However, little is known about the intrinsic signaling pathway that elicits innate immune genes during aging. Here using Drosophila melanogaster, we profile the microRNA targetomes in young and aged animals, and reveal Dawdle (Daw), an activin-like ligand of the TGF-β pathway, as a physiological target of microRNA-252 (miR-252). We show that miR-252 cooperates with Forkhead box O (FoxO), a conserved transcriptional factor implicated in aging, to repress Daw. Unopposed Daw triggers hyper activation of innate immune genes coupled with a decline in organismal survival. Using adult muscle tissues, single-cell sequencing analysis describes that Daw and its downstream innate immune genes are expressed in distinct cell types, suggesting a cell non-autonomous mode of regulation. We further determine the genetic cascade by which Daw signaling leads to increased Kenny/IKKγ protein, which in turn activates Relish/NF-κB protein and consequentially innate immune genes. Finally, transgenic increase of miR-252 and FoxO pathway factors in wild-type Drosophila extends lifespan and mitigates the induction of innate immune genes in aging. Together, we propose that miR-252 and FoxO promote healthy longevity by cooperative inhibition on Daw mediated inflammaging.

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In vivo Optical Access to Olfactory Sensory Neurons in the Mouse Olfactory Epithelium

BIO-PROTOCOL ◽

10.21769/bioprotoc.4055 ◽

2021 ◽

Vol 11 (12) ◽

Author(s):

Shigenori Inagaki ◽

Ryo Iwata ◽

Takeshi Imai

Keyword(s):

Sensory Neurons ◽

Olfactory Epithelium ◽

Olfactory Sensory Neurons ◽

Optical Access

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Aversive Learning Increases Release Probability of Olfactory Sensory Neurons

10.1101/642751 ◽

2019 ◽

Author(s):

Janardhan P. Bhattarai ◽

Mary Schreck ◽

Andrew H. Moberly ◽

Wenqin Luo ◽

Minghong Ma

Keyword(s):

Sensory Neurons ◽

Receptor Expression ◽

Olfactory Sensory Neurons ◽

Aversive Learning ◽

Sensory Stimuli ◽

Release Probability ◽

Synaptic Release ◽

Underlying Mechanisms ◽

Peripheral Sensory ◽

Cortical Influence

AbstractPredicting danger from previously associated sensory stimuli is essential for survival. Contributions from altered peripheral sensory inputs are implicated in this process, but the underlying mechanisms remain elusive. Here we use the mammalian olfactory system to investigate such mechanisms. Primary olfactory sensory neurons (OSNs) project their axons directly to the olfactory bulb (OB) glomeruli where their synaptic release is subject to local and cortical influence and neuromodulation. Pairing optogenetic activation of a single glomerulus with foot shock in mice induces freezing to the light stimulation alone during fear retrieval. This is accompanied by an increase in OSN release probability and a reduction in GABAB receptor expression in the conditioned glomerulus. Furthermore, freezing time is positively correlated with the release probability of OSNs in fear conditioned mice. These results suggest that aversive learning increases peripheral olfactory inputs at the first synapse, which may contribute to the behavioral outcome.

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Unique molecular markers for GC-D-expressing olfactory sensory neurons and chemosensory neurons of the Grueneberg ganglion

10.1101/346502 ◽

2018 ◽

Cited By ~ 1

Author(s):

Zhi Huang ◽

Arthur D. Zimmerman ◽

Steven D. Munger

Keyword(s):

Molecular Markers ◽

Sensory Neurons ◽

Neural Circuitry ◽

Olfactory Sensory Neurons ◽

Molecular Signatures ◽

Main Olfactory Bulb ◽

Chemosensory Neurons ◽

Main Olfactory Epithelium ◽

Grueneberg Ganglion ◽

Necklace Glomeruli

ABSTRACTThe main olfactory bulb (MOB) is differentiated into subregions based on their innervation by molecularly distinct chemosensory neurons. For example, olfactory sensory neurons (OSNs) that employ a cGMP-mediated transduction cascade – guanylyl-cyclase D-expressing (GC-D+) OSNs of the main olfactory epithelium (MOE) and chemosensory neurons of the Grueneberg ganglion (GGNs) – project to distinct groups of “necklace” glomeruli encircling the caudal MOB. To better understand the unique functionality and neural circuitry of the necklace glomeruli and their associated sensory neurons, we sought to identify additional molecular markers that would differentiate GC-D+ OSNs and GGNs as well as their target glomeruli. We found in mouse that GC-D+ OSNs, but not other MOE OSNs or GGNs, express the neuropeptide CART (cocaine- and amphetamine-regulated transcript). Both GC-D+ OSNs and GGNs, but not other MOE OSNs, express the Ca2+/calmodulin-dependent phosphodiesterase Pde1a, which is immunolocalized throughout the dendrites, somata and axons of these neurons. Stronger Pde1a immunolabeling in necklace glomeruli innervated by GGNs than in those innervated by GC-D+ OSNs suggests either greater Pde1a expression in individual GGNs than in GC-D+ OSNs or a difference in sensory neuron innervation density between the two types of necklace glomeruli. Together, the unique molecular signatures of GC-D+ OSNs, GGNs and their MOB targets offer important tools for understanding the processing of chemosensory information by olfactory subsystems associated with the necklace glomeruli.

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