scholarly journals Spontaneously active NaV1.5 sodium channels may underlie odor sensitivity

2016 ◽  
Vol 116 (2) ◽  
pp. 776-783 ◽  
Author(s):  
Vincent E. Dionne
Keyword(s):  
Membrane Potential ◽  
Sodium Channels ◽  
Sensory Neurons ◽  
Olfactory System ◽  
Cellular Response ◽  
Olfactory Sensory Neurons ◽  
Spontaneous Firing ◽  
Channel Activity ◽  
Recent Account ◽  
Odor Sensitivity

The olfactory system is remarkably sensitive to airborne odor molecules, but precisely how very low odor concentrations bordering on just a few molecules per olfactory sensory neuron can trigger graded changes in firing is not clear. This report reexamines signaling in olfactory sensory neurons in light of the recent account of NaV1.5 sodium channel-mediated spontaneous firing. Using a model of spontaneous channel activity, the study shows how even submillivolt changes in membrane potential elicited by odor are expected to cause meaningful changes in NaV1.5-dependent firing. The results suggest that the random window currents of NaV1.5 channels may underpin not only spontaneous firing in olfactory sensory neurons but the cellular response to odor as well, thereby ensuring the robustness and sensitivity of signaling that is especially important for low odor concentrations.

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 NaV1.5 sodium channel window currents contribute to spontaneous firing in olfactory sensory neurons

2014 ◽  
Vol 112 (5) ◽  
pp. 1091-1104 ◽  
Author(s):  
Christopher T. Frenz ◽  
Anne Hansen ◽  
Nicholas D. Dupuis ◽  
Nicole Shultz ◽  
Simon R. Levinson ◽  
...  
Keyword(s):  
Spontaneous Activity ◽  
Sensory Neurons ◽  
Immunohistochemical Analysis ◽  
Resting Potential ◽  
Olfactory Sensory Neurons ◽  
Spontaneous Firing ◽  
Whole Cell Patch Clamp ◽  
Window Current ◽  
Olfactory Tissue ◽  
Α Subunits

Olfactory sensory neurons (OSNs) fire spontaneously as well as in response to odor; both forms of firing are physiologically important. We studied voltage-gated Na+ channels in OSNs to assess their role in spontaneous activity. Whole cell patch-clamp recordings from OSNs demonstrated both tetrodotoxin-sensitive and tetrodotoxin-resistant components of Na+ current. RT-PCR showed mRNAs for five of the nine different Na+ channel α-subunits in olfactory tissue; only one was tetrodotoxin resistant, the so-called cardiac subtype NaV1.5. Immunohistochemical analysis indicated that NaV1.5 is present in the apical knob of OSN dendrites but not in the axon. The NaV1.5 channels in OSNs exhibited two important features: 1) a half-inactivation potential near −100 mV, well below the resting potential, and 2) a window current centered near the resting potential. The negative half-inactivation potential renders most NaV1.5 channels in OSNs inactivated at the resting potential, while the window current indicates that the minor fraction of noninactivated NaV1.5 channels have a small probability of opening spontaneously at the resting potential. When the tetrodotoxin-sensitive Na+ channels were blocked by nanomolar tetrodotoxin at the resting potential, spontaneous firing was suppressed as expected. Furthermore, selectively blocking NaV1.5 channels with Zn2+ in the absence of tetrodotoxin also suppressed spontaneous firing, indicating that NaV1.5 channels are required for spontaneous activity despite resting inactivation. We propose that window currents produced by noninactivated NaV1.5 channels are one source of the generator potentials that trigger spontaneous firing, while the upstroke and propagation of action potentials in OSNs are borne by the tetrodotoxin-sensitive Na+ channel subtypes.

scholarly journals Distinct signaling of Drosophila chemoreceptors in olfactory sensory neurons

2016 ◽  
Vol 113 (7) ◽  
pp. E902-E911 ◽  
Author(s):  
Li-Hui Cao ◽  
Bi-Yang Jing ◽  
Dong Yang ◽  
Xiankun Zeng ◽  
Ying Shen ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Neural Activity ◽  
Odorant Receptors ◽  
Olfactory Sensory Neurons ◽  
Intracellular Recordings ◽  
Patch Clamp Technique ◽  
Current Voltage ◽  
Opposing Effects ◽  
Induced Changes ◽  
Odor Sensitivity

In Drosophila, olfactory sensory neurons (OSNs) rely primarily on two types of chemoreceptors, odorant receptors (Ors) and ionotropic receptors (Irs), to convert odor stimuli into neural activity. The cellular signaling of these receptors in their native OSNs remains unclear because of the difficulty of obtaining intracellular recordings from Drosophila OSNs. Here, we developed an antennal preparation that enabled the first recordings (to our knowledge) from targeted Drosophila OSNs through a patch-clamp technique. We found that brief odor pulses triggered graded inward receptor currents with distinct response kinetics and current–voltage relationships between Or- and Ir-driven responses. When stimulated with long-step odors, the receptor current of Ir-expressing OSNs did not adapt. In contrast, Or-expressing OSNs showed a strong Ca2+-dependent adaptation. The adaptation-induced changes in odor sensitivity obeyed the Weber–Fechner relation; however, surprisingly, the incremental sensitivity was reduced at low odor backgrounds but increased at high odor backgrounds. Our model for odor adaptation revealed two opposing effects of adaptation, desensitization and prevention of saturation, in dynamically adjusting odor sensitivity and extending the sensory operating range.

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