scholarly journals Notch signaling determines cell-fate specification of the two main types of vomeronasal neurons of rodents.

2021 ◽  
Author(s):  
Raghu Ram Katreddi ◽  
Ed Zandro M Taroc ◽  
Sawyer M Hicks ◽  
Jennifer M Lin ◽  
Shuting Liu ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Cell Fate ◽  
Sensory Neurons ◽  
Sexual Behaviors ◽  
Olfactory System ◽  
Mammalian Species ◽  
Sequencing Data ◽  
Terrestrial Vertebrates ◽  
Main Olfactory Epithelium ◽  
Vomeronasal Receptors

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.

scholarly journals Extinction reverses olfactory fear-conditioned increases in neuron number and glomerular size

2015 ◽  
Vol 112 (41) ◽  
pp. 12846-12851 ◽  
Author(s):  
Filomene G. Morrison ◽  
Brian G. Dias ◽  
Kerry J. Ressler
Keyword(s):  
Olfactory Bulb ◽  
Learning And Memory ◽  
Olfactory Epithelium ◽  
Olfactory System ◽  
Structural Changes ◽  
Freezing Behavior ◽  
Extinction Training ◽  
Odor Stimulus ◽  
Main Olfactory Epithelium ◽  
Odor Learning

Although much work has investigated the contribution of brain regions such as the amygdala, hippocampus, and prefrontal cortex to the processing of fear learning and memory, fewer studies have examined the role of sensory systems, in particular the olfactory system, in the detection and perception of cues involved in learning and memory. The primary sensory receptive field maps of the olfactory system are exquisitely organized and respond dynamically to cues in the environment, remaining plastic from development through adulthood. We have previously demonstrated that olfactory fear conditioning leads to increased odorant-specific receptor representation in the main olfactory epithelium and in glomeruli within the olfactory bulb. We now demonstrate that olfactory extinction training specific to the conditioned odor stimulus reverses the conditioning-associated freezing behavior and odor learning-induced structural changes in the olfactory epithelium and olfactory bulb in an odorant ligand-specific manner. These data suggest that learning-induced freezing behavior, structural alterations, and enhanced neural sensory representation can be reversed in adult mice following extinction training.

scholarly journals Region-specific amyloid-β accumulation in the olfactory system influences olfactory sensory neuronal dysfunction in 5xFAD mice

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Gowoon Son ◽  
Seung-Jun Yoo ◽  
Shinwoo Kang ◽  
Ameer Rasheed ◽  
Da Hae Jung ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Sensory Neurons ◽  
Olfactory System ◽  
Amyloid Β ◽  
Olfactory Sensory Neurons ◽  
Basal Cells ◽  
Irreversible Damage ◽  
5Xfad Mouse ◽  
Peripheral Areas ◽  
5Xfad Mice

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.

scholarly journals Region specific amyloid-β accumulation in the olfactory system influences olfactory sensory neuronal dysfunction in 5xFAD mice

2020 ◽  
Author(s):  
Gowoon Son ◽  
Seung-Jun Yoo ◽  
Shinwoo Kang ◽  
Ameer Rasheed ◽  
Da Hae Jung ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Sensory Neurons ◽  
Olfactory System ◽  
Amyloid Β ◽  
Olfactory Sensory Neurons ◽  
Basal Cells ◽  
Irreversible Damage ◽  
5Xfad Mouse ◽  
Peripheral Areas ◽  
5Xfad Mice

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. 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 three-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.

scholarly journals Region Specific Amyloid-β Accumulation in Olfactory Sensory Neurons Influences Ecto-Ventral Olfactory Dysfunction in 5xFAD Mice

2020 ◽  
Author(s):  
Gowoon Son ◽  
Seung-Jun Yoo ◽  
Shinwoo Kang ◽  
Ameer Rasheed ◽  
Da Hae Jung ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Sensory Neurons ◽  
Olfactory Epithelium ◽  
Olfactory System ◽  
Amyloid Β ◽  
Olfactory Dysfunction ◽  
Olfactory Sensory Neurons ◽  
Basal Cells ◽  
Irreversible Damage ◽  
5Xfad Mouse

Abstract Background: Hyposmia in Alzheimer’s disease (AD) is a typical early symptom according to numerous previous clinical studies. Although the causes of damage have been proposed in every olfactory system including olfactory epithelium, olfactory bulb and olfactory cortex, the main causes of AD- related hyposmia are largely unknown. Methods: We here focused on peripheral olfactory sensory neurons (OSNs) and delved deeper into the direct relationship between pathophysiological and behavioral results using odorants. We also histologically confirmed the pathological changes in three-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 anatomical plane. Results: We observed the odorant group, which 5xFAD mouse could not detect, also neither did physiologically activate the OSNs that propagate to the ventral olfactory bulb. Interestingly, the amount of accumulated amyloid-β (Aβ) was high in the ecto-ventrally located OSNs that showed reduced responses to odorants. We also observed irreversible damage to the ecto-region of the olfactory epithelium by measuring 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 the AD-related hyposmia, a characteristic of early AD.

scholarly journals Region specific amyloid-β accumulation in the olfactory system influences olfactory sensory neuronal dysfunction in 5xFAD mice

2020 ◽  
Author(s):  
Gowoon Son ◽  
Seung-Jun Yoo ◽  
Shinwoo Kang ◽  
Ameer Rasheed ◽  
Da Hae Jung ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Sensory Neurons ◽  
Olfactory System ◽  
Amyloid Β ◽  
Olfactory Sensory Neurons ◽  
Basal Cells ◽  
Irreversible Damage ◽  
5Xfad Mouse ◽  
Peripheral Areas ◽  
5Xfad Mice

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. 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 three-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.

scholarly journals Zonal organization of the mammalian main and accessory olfactory systems

2000 ◽  
Vol 355 (1404) ◽  
pp. 1801-1812 ◽  
Author(s):  
Kensaku Mori ◽  
Harald von Campenhausen ◽  
Yoshihiro Yoshihara
Keyword(s):  
Olfactory Bulb ◽  
Sensory Neurons ◽  
Olfactory System ◽  
Expression Patterns ◽  
Odorant Receptors ◽  
Accessory Olfactory Bulb ◽  
Basal Zone ◽  
Olfactory Systems ◽  
Tufted Cells ◽  
Zonal Organization

Zonal organization is one of the characteristic features observed in both main and accessory olfactory systems. In the main olfactory system, most of the odorant receptors are classified into four groups according to their zonal expression patterns in the olfactory epithelium. Each group of odorant receptors is expressed by sensory neurons distributed within one of four circumscribed zones. Olfactory sensory neurons in a given zone of the epithelium project their axons to the glomeruli in a corresponding zone of the main olfactory bulb. Glomeruli in the same zone tend to represent similar odorant receptors having similar tuning specificity to odorants. Vomeronasal receptors (or pheromone receptors) are classified into two groups in the accessory olfactory system. Each group of receptors is expressed by vomeronasal sensory neurons in either the apical or basal zone of the vomeronasal epithelium. Sensory neurons in the apical zone project their axons to the rostral zone of the accessory olfactory bulb and form synaptic connections with mitral–tufted cells belonging to the rostral zone. Signals originated from basal zone sensory neurons are sent to mitral–tufted cells in the caudal zone of the accessory olfactory bulb. We discuss functional implications of the zonal organization in both main and accessory olfactory systems.

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

2020 ◽  
Vol 6 (22) ◽  
pp. eaaz6868
Author(s):  
Wen Mai Wong ◽  
Jie Cao ◽  
Xingjian Zhang ◽  
Wayne I. Doyle ◽  
Luis L. Mercado ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Reproductive Behavior ◽  
Olfactory System ◽  
Cell Capture ◽  
Biological Mechanisms ◽  
New Approach ◽  
Vomeronasal Receptors ◽  
Receptor Interactions ◽  
Specific Receptors ◽  
Accessory Olfactory System

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.

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

2016 ◽  
Vol 113 (39) ◽  
pp. 10974-10979 ◽  
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.

scholarly journals Map-independent representation of an aggression-promoting social cue in the main olfactory pathway

2021 ◽  
Author(s):  
Annika Cichy ◽  
Adam Dewan ◽  
Jingji Zhang ◽  
Sarah Kaye ◽  
Tiffany Teng ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Sensory Neurons ◽  
Mammalian Species ◽  
Olfactory Sensory Neurons ◽  
Olfactory Pathway ◽  
Male Aggression ◽  
Transgenic Expression ◽  
Mouse Urine ◽  
State Dependent ◽  
Specific Odor

While the olfactory system is required for proper social behaviors, the molecular basis for how social cues are detected via the main olfactory pathway of mammals is not well-characterized. Trimethylamine is a volatile, sex-specific odor found in adult male mouse urine that selectively activates main olfactory sensory neurons that express trace amine-associated receptor 5 (TAAR5). Here we show that trimethylamine, acting via TAAR5, elicits state-dependent attraction or aversion in male mice and drives inter-male aggression. Genetic knockout of TAAR5 significantly reduces aggression-related behaviors, while adding trimethylamine augments aggressive behavior towards juvenile males. We further show that transgenic expression of TAAR5 specifically in olfactory sensory neurons rescues aggressive behaviors in knockout mice, despite extensive remapping of TAAR5 projections to the olfactory bulb. Our results identify a specific main olfactory input that detects a prominent male-specific odor to induce inter-male aggression in a mammalian species and reveal that apparently innate behavioral responses are independent of patterned glomerular input to the olfactory bulb.

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