Linear correlation between the number of olfactory sensory neurons expressing a given mouse odorant receptor gene and the total volume of the corresponding glomeruli in the olfactory bulb

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.

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Odorant responses of olfactory sensory neurons expressing the odorant receptor MOR23: A patch clamp analysis in gene-targeted mice

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0508491103 ◽

2006 ◽

Vol 103 (6) ◽

pp. 1970-1975 ◽

Cited By ~ 96

Author(s):

X. Grosmaitre ◽

A. Vassalli ◽

P. Mombaerts ◽

G. M. Shepherd ◽

M. Ma

Keyword(s):

Patch Clamp ◽

Sensory Neurons ◽

Odorant Receptor ◽

Olfactory Sensory Neurons

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Widespread inhibition, antagonism, and synergy in mouse olfactory sensory neurons in vivo

10.1101/803908 ◽

2019 ◽

Cited By ~ 1

Author(s):

Shigenori Inagaki ◽

Ryo Iwata ◽

Masakazu Iwamoto ◽

Takeshi Imai

Keyword(s):

Sensory Neurons ◽

Calcium Imaging ◽

Odorant Receptor ◽

Sensory Information ◽

Olfactory Sensory Neurons ◽

Axon Terminals ◽

Two Photon ◽

Odor Mixtures ◽

The Brain

SUMMARYSensory information is selectively or non-selectively inhibited and enhanced in the brain, but it remains unclear whether this occurs commonly at the peripheral stage. Here, we performed two-photon calcium imaging of mouse olfactory sensory neurons (OSNs) in vivo and found that odors produce not only excitatory but also inhibitory responses at their axon terminals. The inhibitory responses remained in mutant mice, in which all possible sources of presynaptic lateral inhibition were eliminated. Direct imaging of the olfactory epithelium revealed widespread inhibitory responses at OSN somata. The inhibition was in part due to inverse agonism toward the odorant receptor. We also found that responses to odor mixtures are often suppressed or enhanced in OSNs: Antagonism was dominant at higher odor concentrations, whereas synergy was more prominent at lower odor concentrations. Thus, odor responses are extensively tuned by inhibition, antagonism, and synergy, at the early peripheral stage, contributing to robust odor representations.

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Molecular Biology of Vertebrate Olfactory Receptors and Circuits

Oxford Research Encyclopedia of Neuroscience ◽

10.1093/acrefore/9780190264086.013.92 ◽

2021 ◽

Author(s):

Richard P. Tucker ◽

Qizhi Gong

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Olfactory Bulb ◽

Gene Family ◽

Sensory Neuron ◽

Sensory Neurons ◽

Odorant Receptor ◽

Vomeronasal Organ ◽

Odorant Receptors ◽

The Central Nervous System

Animals use their olfactory system for the procurement of food, the detection of danger, and the identification of potential mates. In vertebrates, the olfactory sensory neuron has a single apical dendrite that is exposed to the environment and a single basal axon that projects to the central nervous system (i.e., the olfactory bulb). The first odorant receptors to be discovered belong to an enormous gene family encoding G protein-coupled seven transmembrane domain proteins. Odorant binding to these classical odorant receptors initiates a GTP-dependent signaling cascade that uses cAMP as a second messenger. Subsequently, additional types of odorant receptors using different signaling pathways have been identified. While most olfactory sensory neurons are found in the olfactory sensory neuroepithelium, others are found in specialized olfactory subsystems. In rodents, the vomeronasal organ contains neurons that recognize pheromones, the septal organ recognizes odorant and mechanical stimuli, and the neurons of the Grüneberg ganglion are sensitive to cool temperatures and certain volatile alarm signals. Within the olfactory sensory neuroepithelium, each sensory neuron expresses a single odorant receptor gene out of the large gene family; the axons of sensory neurons expressing the same odorant receptor typically converge onto a pair of glomeruli at the periphery of the olfactory bulb. This results in the transformation of olfactory information into a spatially organized odortopic map in the olfactory bulb. The axons originating from the vomeronasal organ project to the accessory olfactory bulb, whereas the axons from neurons in the Grüneberg ganglion project to 10 specific glomeruli found in the caudal part of the olfactory bulb. Within a glomerulus, the axons originating from olfactory sensory neurons synapse on the dendrites of olfactory bulb neurons, including mitral and tufted cells. Mitral cells and tufted cells in turn project directly to higher brain centers (e.g., the piriform cortex and olfactory tubercle). The integration of olfactory information in the olfactory cortices and elsewhere in the central nervous system informs and directs animal behavior.

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