scholarly journals Physiology-forward identification of bile acid sensitive vomeronasal receptors

2019 ◽  
Author(s):  
Wen Mai Wong ◽  
Jie Cao ◽  
Xingjian Zhang ◽  
Wayne I. Doyle ◽  
Luis L. Mercado ◽  
...  

Abstract/SummaryThe mouse accessory olfactory system (AOS) supports social and reproductive behavior through the sensation of environmental chemosignals. A growing number of excreted steroids have been shown to be potent AOS cues, including bile acids (BAs) found in feces. As is still the case with most AOS ligands, the specific receptors used by vomeronasal sensory neurons (VSNs) to detect BAs remain unknown. To identify VSN BA receptors, we first performed a deep analysis of VSN BA tuning using volumetric GCaMP6f/s Ca2+ imaging. These experiments revealed both broadly and narrowly tuned populations of BA-receptive VSNs with sub-micromolar sensitivities. We then developed a new physiology-forward approach for identifying AOS ligand-receptor interactions, which we call Fluorescence Live Imaging for Cell Capture and RNA-seq, or FLICCR-seq. FLICCR-seq analysis revealed 5 specific V1R-family receptors enriched in BA-sensitive VSNs. These studies introduce a powerful new approach for ligand-receptor matching and reveal biological mechanisms underlying mammalian BA chemosensation.

2020 ◽  
Vol 6 (22) ◽  
pp. eaaz6868
Author(s):  
Wen Mai Wong ◽  
Jie Cao ◽  
Xingjian Zhang ◽  
Wayne I. Doyle ◽  
Luis L. Mercado ◽  
...  

The mouse accessory olfactory system (AOS) supports social and reproductive behavior through the sensation of environmental chemosignals. A growing number of excreted steroids have been shown to be potent AOS cues, including bile acids (BAs) found in feces. As is still the case with most AOS ligands, the specific receptors used by vomeronasal sensory neurons (VSNs) to detect BAs remain unknown. To identify VSN BA receptors, we first performed a deep analysis of VSN BA tuning using volumetric GCaMP6f/s Ca2+ imaging. These experiments revealed multiple populations of BA-receptive VSNs with submicromolar sensitivities. We then developed a new physiology-forward approach for identifying AOS ligand-receptor interactions, which we call Fluorescence Live Imaging for Cell Capture and RNA sequencing, or FLICCR-seq. FLICCR-seq analysis revealed five specific V1R family receptors enriched in BA-sensitive VSNs. These studies introduce a powerful new approach for ligand-receptor matching and reveal biological mechanisms underlying mammalian BA chemosensation.


2021 ◽  
Author(s):  
Shahab Bahreini Jangjoo ◽  
Jennifer M Lin ◽  
Farhood Etaati ◽  
Sydney Fearnley ◽  
Jean-François Cloutier ◽  
...  

Abstract Glomeruli are neuropil rich regions of the main or accessory olfactory bulbs where the axons of olfactory or vomeronasal neurons and dendrites of mitral/tufted cells form synaptic connections. In the main olfactory system olfactory sensory neurons (OSNs) expressing the same receptor innervate one or two glomeruli. However, in the accessory olfactory system, vomeronasal sensory neurons (VSNs) expressing the same receptor can innervate up to 30 different glomeruli in the accessory olfactory bulb (AOB). Genetic mutation disrupting genes with a role in defining the identity/diversity of olfactory and vomeronasal neurons can alter the number and size of glomeruli. Interestingly, two cell surface molecules, Kirrel2 and Kirrel3, have been indicated as playing a critical role in the organization of axons into glomeruli in the AOB. Being able to quantify differences in glomeruli features, such as number, size or immunoreactivity for specific markers, is an important experimental approach to validate the role of specific genes in controlling neuronal connectivity and circuit formation in either control or mutant animals. Since the manual recognition and quantification of glomeruli on digital images is a challenging and time-consuming task, we generated a program in Python able to identify glomeruli in digital images and quantify their properties, such as size, number, and pixel intensity. Validation of our program indicates that our script is a fast and suitable tool for high throughput quantification of glomerular features of mouse lines with different genetic makeup.


2021 ◽  
Author(s):  
Shahab Bahreini Jangjoo ◽  
Jennifer M Lin ◽  
Farhood Etaati ◽  
Sydney Fearnley ◽  
Jean-Francois Cloutier ◽  
...  

Glomeruli are neuropil rich regions of the main or accessory olfactory bulbs where the axons of olfactory or vomeronasal neurons and dendrites of mitral/tufted cells form synaptic connections. In the main olfactory system olfactory sensory neurons (OSNs) expressing the same receptor innervate one or two glomeruli. However, in the accessory olfactory system, vomeronasal sensory neurons (VSNs) expressing the same receptor can innervate up to 30 different glomeruli in the accessory olfactory bulb (AOB). Genetic mutation disrupting genes with a role in defining the identity/diversity of olfactory and vomeronasal neurons can alter number and size of glomeruli. Interestingly, two cell surface molecules, Kirrel2 and Kirrel3, have been indicated to play a critical role in the organization of axons into glomeruli in the AOB. Being able to quantify differences in glomeruli features such as number, size or immunoreactivity for specific markers is an important experimental approach to validate the role of specific genes in controlling neuronal connectivity and circuit formation in control or mutant animals. Since the manual recognition and quantification of glomeruli on digital images is a challenging and time-consuming task, we generated a program in Python able to identify glomeruli in digital images and quantify their properties, such as size, number, and pixel intensity. Validation of our program indicates that our script is a fast and suitable tool for high throughput quantification of glomerular features of mouse lines with different genetic makeup.


2021 ◽  
Author(s):  
Raghu Ram Katreddi ◽  
Ed Zandro M Taroc ◽  
Sawyer M Hicks ◽  
Jennifer M Lin ◽  
Shuting Liu ◽  
...  

The ability of terrestrial vertebrates to find food, mating partners and to avoid predators heavily relies on the detection of chemosensory information from the environment. The olfactory system of most vertebrate species comprises two distinct chemosensory systems usually referred to as the main and the accessory olfactory system. Olfactory sensory neurons of the main olfactory epithelium detect and transmit odor information to main olfactory bulb (MOB), while the chemosensory neurons of the vomeronasal organ detect semiochemicals responsible for social and sexual behaviors and transmit information to the accessory olfactory bulb (AOB). The vomeronasal sensory epithelium (VNE) of most mammalian species contains uniform vomeronasal (VN) system with vomeronasal sensory neurons (VSNs) expressing vomeronasal receptors of the V1R family. However, rodents and some marsupials have developed a more complex binary VN system, where VNO containing a second main type of VSNs expressing vomeronasal receptors of the V2R family is identified. In mice, V1R and V2R VSNs form from a common pool of progenitors but have distinct differentiation programs. As they mature, they segregate in different regions of the VNE and connect with different parts of the AOB. How these two main types of VSNs are formed has never been addressed. In this study, using single cell RNA sequencing data, we identified differential expression of Notch1 receptor and Dll4 ligand among the neuronal precursors at the VSN dichotomy. We further demonstrated with loss of function (LOF) and gain of function (GOF) studies that Dll4-Notch1 signaling plays a crucial role in triggering the binary dichotomy between the two main types of VSNs in mice.


Mathematics ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 323
Author(s):  
Martina Nicoletti ◽  
Letizia Chiodo ◽  
Alessandro Loppini

Mechanosensing is a key feature through which organisms can receive inputs from the environment and convert them into specific functional and behavioral outputs. Mechanosensation occurs in many cells and tissues, regulating a plethora of molecular processes based on the distribution of forces and stresses both at the cell membrane and at the intracellular organelles levels, through complex interactions between cells’ microstructures, cytoskeleton, and extracellular matrix. Although several primary and secondary mechanisms have been shown to contribute to mechanosensation, a fundamental pathway in simple organisms and mammals involves the presence of specialized sensory neurons and the presence of different types of mechanosensitive ion channels on the neuronal cell membrane. In this contribution, we present a review of the main ion channels which have been proven to be significantly involved in mechanotransduction in neurons. Further, we discuss recent studies focused on the biological mechanisms and modeling of mechanosensitive ion channels’ gating, and on mechanotransduction modeling at different scales and levels of details.


2021 ◽  
Vol 383 (1) ◽  
pp. 143-148
Author(s):  
Shadi Jafari ◽  
Mattias Alenius

AbstractOlfactory perception is very individualized in humans and also in Drosophila. The process that individualize olfaction is adaptation that across multiple time scales and mechanisms shape perception and olfactory-guided behaviors. Olfactory adaptation occurs both in the central nervous system and in the periphery. Central adaptation occurs at the level of the circuits that process olfactory inputs from the periphery where it can integrate inputs from other senses, metabolic states, and stress. We will here focus on the periphery and how the fast, slow, and persistent (lifelong) adaptation mechanisms in the olfactory sensory neurons individualize the Drosophila olfactory system.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Gowoon Son ◽  
Seung-Jun Yoo ◽  
Shinwoo Kang ◽  
Ameer Rasheed ◽  
Da Hae Jung ◽  
...  

Abstract Background Hyposmia in Alzheimer’s disease (AD) is a typical early symptom according to numerous previous clinical studies. Although amyloid-β (Aβ), which is one of the toxic factors upregulated early in AD, has been identified in many studies, even in the peripheral areas of the olfactory system, the pathology involving olfactory sensory neurons (OSNs) remains poorly understood. Methods Here, we focused on peripheral olfactory sensory neurons (OSNs) and delved deeper into the direct relationship between pathophysiological and behavioral results using odorants. We also confirmed histologically the pathological changes in 3-month-old 5xFAD mouse models, which recapitulates AD pathology. We introduced a numeric scale histologically to compare physiological phenomenon and local tissue lesions regardless of the anatomical plane. Results We observed the odorant group that the 5xFAD mice showed reduced responses to odorants. These also did not physiologically activate OSNs that propagate their axons to the ventral olfactory bulb. Interestingly, the amount of accumulated amyloid-β (Aβ) was high in the OSNs located in the olfactory epithelial ectoturbinate and the ventral olfactory bulb glomeruli. We also observed irreversible damage to the ectoturbinate of the olfactory epithelium by measuring the impaired neuronal turnover ratio from the basal cells to the matured OSNs. Conclusions Our results showed that partial and asymmetrical accumulation of Aβ coincided with physiologically and structurally damaged areas in the peripheral olfactory system, which evoked hyporeactivity to some odorants. Taken together, partial olfactory dysfunction closely associated with peripheral OSN’s loss could be a leading cause of AD-related hyposmia, a characteristic of early AD.


Author(s):  
H. Kaba ◽  
C.-S. Li ◽  
E. B. Keverne ◽  
H. Saito ◽  
K. Seto

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