Olfactory bulb is a critical component in encoding and processing olfactory signals, characterized by its intricate neural projections and networks dedicated to this function. It has been found that descending neural projections from the olfactory cortex and other advanced brain regions can modulate the excitability of olfactory bulb output neurons in the olfactory bulb, either directly or indirectly, which can further influence olfactory discrimination, learning, and other abilities. In recent years, advancements in optogenetic technology have facilitated extensive application of neuron manipulation for studying neural circuits, thereby greatly accelerating research into olfactory mechanisms. This review summarizes the latest research progress on the regulatory effects of neural projections from the olfactory cortex, basal forebrain, raphe nucleus, and locus coeruleus on olfactory bulb function. Furthermore, the important role that photogenetic technology plays in olfactory mechanism research is evaluated. Finally, the existing problems and future development trends in current research are preliminarily proposed and explained. This review aims to provide new insights into the mechanisms underlying olfactory neural regulation as well as applications of optogenetic technology, which are crucial for advancing the research on olfactory mechanism and the application of optogenetic technology.
Olfactory Bulb/physiology* ; Optogenetics/methods* ; Animals ; Humans ; Olfactory Pathways/physiology* ; Olfactory Cortex/physiology* ; Smell/physiology*

气味是评价食品新鲜度最重要的参数之一。当气味以其自然浓度存在时，会在嗅觉系统中引发不同的神经活动模式。本研究提出了一种通过检测食物气味进行食物检测与评价的在体生物传感系统。我们通过将多通道微电极植入在清醒大鼠嗅球的僧帽/丛状细胞层上，进而对神经信号进行实时检测。结果表明，不同的气味可以引起不同的神经振荡活动，每个僧帽/丛状细胞会表现出特定气味的锋电位发放模式。单个大鼠的少量细胞携带足够的信息，可以根据锋电位发放频率变化率的极坐标图来区分不同储存天数的食物。此外，研究表明气味刺激后，β振荡比γ振荡表现出更特异的气味响应模式，这表明β振荡在气味识别中起着更重要的作用。综上，本研究提出的在体神经接口为评估食品新鲜度提供了一种可行性方法。
Olfactory Bulb ; Odorants ; Smell

Objective: To investigate the effects of dopamine on olfactory function and inflammatory injury of olfactory bulb in mice with allergic rhinitis (AR). Methods: AR mouse model was established by using ovalbumin (OVA), and the mice were divided into two groups: olfactory dysfunction (OD) group and without OD group through buried food pellet test (BFPT). The OD mice were randomly divided into 2 groups, and OVA combined with dopamine (3, 6, 9 and 12 days, respectively) or OVA combined with an equal amount of PBS (the same treatment time) was administered nasally. The olfactory function of mice was evaluated by BFPT. The number of eosinophils and goblet cells in the nasal mucosa were detected by HE and PAS staining. Western blotting, immunohistochemistry or immunofluorescence were used to detect the expression of olfactory marker protein (OMP) in olfactory epithelium, the important rate-limiting enzyme tyrosine hydroxylase (TH) of dopamine, and the marker proteins glial fibrillary acidic protein (GFAP) and CD11b of glial cell in the olfactory bulb. TUNEL staining was used to detect the damage of the olfactory bulb. SPSS 26.0 software was used for statistical analysis. Results: AR mice with OD had AR pathological characteristics. Compared with AR mice without OD, the expression of OMP in olfactory epithelium of AR mice with OD was reduced (F=26.09, P<0.05), the expression of GFAP and CD11b in the olfactory bulb was increased (F value was 38.95 and 71.71, respectively, both P<0.05), and the expression of TH in the olfactory bulb was decreased (F=77.00, P<0.05). Nasal administration of dopamine could shorten the time of food globule detection in mice to a certain extent, down-regulate the expression of GFAP and CD11b in the olfactory bulb (F value was 6.55 and 46.11, respectively, both P<0.05), and reduce the number of apoptotic cells in the olfactory bulb (F=25.64, P<0.05). But dopamine had no significant effect on the number of eosinophils and goblet cells in nasal mucosa (F value was 36.26 and 19.38, respectively, both P>0.05), and had no significant effect on the expression of OMP in the olfactory epithelium (F=55.27, P>0.05). Conclusion: Dopamine can improve olfactory function in mice with AR to a certain extent, possibly because of inhibiting the activation of glial cells in olfactory bulb and reducing the apoptotic injury of olfactory bulb cells.
Animals ; Disease Models, Animal ; Dopamine ; Humans ; Mice ; Mice, Inbred BALB C ; Nasal Mucosa/metabolism* ; Olfactory Bulb/pathology* ; Ovalbumin ; Rhinitis, Allergic/metabolism*

Objective: To report the case of a woman who underwent smell training for post-infectious olfactory dysfunction presumably from COVID-19. Methods: Design: Case Report. Setting: Tertiary Private Training Hospital. Patient: One. Result: A 41-year-old woman who developed olfactory dysfunction attributed to COVID-19 underwent smell training. At baseline, her responses were mostly “no smell,” and those reported as “can smell a bit” were rated as distorted. After three months, she could now smell items that she previously could not smell, but these smells were still distorted. At the time of this writing, she was on her 4th month of smell training. Conclusion Although we cannot rule out spontaneous resolution of anosmia in our patient, we would like to think that smell training contributed to her recovery of smell.
Anosmia ; Anosmia ; Olfactory Bulb ; Olfaction Disorders

Objective: To retrospectively analysely the electrophysiological and imaging features of isolated congenital anosmia (ICA) and to assess the clinical phenotypic characteristics and classification of ICA. Methods: Clinical data of 30 ICA patients in Beijing Anzhen Hospital from 2012 to 2019 was retrospectively reviewed, including 13 males and 17 females, aged (35±19) years. The control group consisted of 30 healthy people from medical examination center, including 13 males and 17 females, aged (39±14) years. The clinical characteristics of ICA were analyzed using Sniffin' Sticks test, olfactory event-related potentials (oERPs), trigeminal event-related potentials (tERP) and olfactory pathway MRI. SPSS 17.0 software was used to compare the difference of olfactory function between the two groups. The correlation between olfactory bulb, olfactory sulcus structure and age was observed, and the clinical phenotype characteristics of ICA patients were analyzed. Results: The subjective olfactory function was completely lost in ICA patients. oERP was absent in all of the ICA patients, but showed normal N₁ and P₂ waves in controls. tERP could be evoked in 63.3% (19/30) of ICA patients, and signals in these patients showed higher amplitude in the N₁ ((-10.33±6.93) μV vs (-5.11±2.71) μV, t=-10.113, P<0.01) and P₂ ((+17.25±8.51) μV vs (+7.31±3.46) μV, t=5.443, P<0.01) waves than that of the controls. Olfactory bulbs were aplastic in 80.0% (24/30) of patients and hypoplastic in 20.0% (6/30) of patients. Fifty-six point seven percent (17/30) of patients had bilateral olfactory sulcus deletion while 43.3% (13/30) had dysplasia, and all of the patients exhibited a depth of olfactory sulcus less than 8 mm. Both the structure of olfactory bulbs and olfactory sulcus were not associated with age for ICA patients (r value was -0.174 and 0.325, respectively, all P>0.05). Conclusions: ICA patients show neurophysiologic deficits and some anatomic differences compared with healthy controls. The absence of oERP combining with a depth of olfactory sulcus less than 8 mm is the important indicator for clinical diagnosis of ICA. The structure of olfactory bulb may be a critical factor for clinical classification of ICA.
Adolescent ; Adult ; Anosmia ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Olfaction Disorders/diagnosis* ; Olfactory Bulb/diagnostic imaging* ; Olfactory Pathways ; Retrospective Studies ; Smell ; Young Adult

Olfactory dysfunction occurs in multiple sclerosis in humans, as well as in an animal model of experimental autoimmune encephalomyelitis (EAE). The aim of this study was to analyze differentially expressed genes (DEGs) in olfactory bulb of EAE-affected mice by next generation sequencing, with a particular focus on changes in olfaction-related signals. EAE was induced in C57BL/6 mice following immunization with myelin oligodendrocyte glycoprotein and adjuvant. Inflammatory lesions were identified in the olfactory bulbs as well as in the spinal cord of immunized mice. Analysis of DEGs in the olfactory bulb of EAE-affected mice revealed that 44 genes were upregulated (and which were primarily related to inflammatory mediators), while 519 genes were downregulated; among the latter, olfactory marker protein and stomatin-like 3, which have been linked to olfactory signal transduction, were significantly downregulated (log2 [fold change] >1 and p-value < 0.05). These findings suggest that inflammation in the olfactory bulb of EAE-affected mice is associated with the downregulation of some olfactory signal transduction genes, particularly olfactory marker protein and stomatin-like 3, which may lead to olfactory dysfunction in an animal model of human multiple sclerosis.
Animals ; Down-Regulation ; Encephalomyelitis, Autoimmune, Experimental ; Gene Expression ; Humans ; Immunization ; Inflammation ; Mice ; Models, Animal ; Multiple Sclerosis ; Myelin-Oligodendrocyte Glycoprotein ; Olfactory Bulb ; Olfactory Marker Protein ; Signal Transduction ; Spinal Cord ; Transcriptome

OBJECTIVES: Parkinson disease (PD) is frequently associated with olfactory disorder at early stage, which is caused by deposition of Lewy bodies emerging from the olfactory bulb to higher olfactory centers. Early detection of olfactory disorder in the patients with PD may lead to the early diagnosis and treatment for this refractory disease. METHODS: Visual analog scale (VAS), Jet Stream Olfactometry, and Japanese smell identification test, Open Essence (OE), were carried out on 39 patients with PD. Thirty-one patients with postviral olfactory disorder (PVOD), which was caused by the olfactory mucosal dysfunction, were also enrolled in this study as control. RESULTS: There were no significant differences in detection thresholds (2.2 vs. 1.4, P=0.13), recognition thresholds (3.9 vs. 3.5, P=0.39) and OE (4.8 vs. 4.2, P=0.47) between PVOD and PD, while VAS scores of PVOD and PD were significantly different (2.0 and 6.2, P<0.01). In OE, significant differences were observed in the accuracy rates of menthol (68% vs. 44%, P=0.04) and Indian ink (42% vs. 15%, P=0.01) between PVOD and PD. Of particular interest, patients with PVOD tended to select “no detectable,” while patients with PD tended to select wrong alternative other than “no smell detected.” CONCLUSION: Discrepancy between VAS and OE, and high selected rates of wrong alternative other than “undetectable” in OE might be significant signs of olfactory dysfunction associated with PD.
Asian Continental Ancestry Group ; Early Diagnosis ; Humans ; Ink ; Lewy Bodies ; Menthol ; Olfactometry ; Olfactory Bulb ; Parkinson Disease ; Rivers ; Smell ; Visual Analog Scale

Parkinson's disease (PD) is a common neurodegenerative disorder arising from an interplay between genetic and environmental risk factors. Studies have suggested that the pathological hallmarks of intraneuronal α-synuclein aggregations may start from the olfactory bulb and the enteric nervous system of the gut and later propagate to the brain via the olfactory tract and the vagus nerve. This hypothesis correlates well with clinical symptoms, such as constipation, that may develop up to 20 years before the onset of PD motor symptoms. Recent interest in the gut–brain axis has led to vigorous research into the gastrointestinal pathology and gut microbiota changes in patients with PD. In this review, we provide current clinical and pathological evidence of gut involvement in PD by summarizing the changes in gut microbiota composition and gut inflammation associated with its pathogenesis.
Brain ; Constipation ; Enteric Nervous System ; Gastrointestinal Microbiome ; Humans ; Inflammation ; Microbiota ; Neurodegenerative Diseases ; Olfactory Bulb ; Parkinson Disease ; Pathology ; Risk Factors ; Vagus Nerve

The hippocampus and olfactory bulb incorporate new neurons migrating from neurogenic regions in the brain. Hippocampal atrophy is evident in numerous neurodegenerative disorders, and altered hippocampal neurogenesis is an early pathological event in Alzheimer's disease. We hypothesized that hippocampal neurogenesis is affected by olfactory stimuli through the neural pathway of olfaction-related memory. In this study, we exposed mice to novel pleasant odors for three weeks and then assessed the number of neurons, non-neuronal cells (mainly glia) and proliferating cells in the hippocampus and olfactory bulb, using the isotropic fractionator method. We found that the odor enrichment significantly increased the neuronal cell numbers in the hippocampus, and promoted cell proliferation and neurogenesis in the olfactory bulb. In contrast, the glial cell numbers remained unchanged in both of the regions. Our results suggest that exposure to novel odor stimuli promotes hippocampal neurogenesis and support the idea that enriched environments may delay the onset or slow down the progression of neurodegenerative disorders.
Alzheimer Disease ; Animals ; Atrophy ; Brain ; Cell Count ; Cell Proliferation ; Hippocampus ; Memory ; Methods ; Mice* ; Neural Pathways ; Neurodegenerative Diseases ; Neurogenesis ; Neuroglia ; Neurons* ; Odors* ; Olfactory Bulb

The olfactory system can detect many odorants with high sensitivity and selectivity based on the expression of nearly a thousand types of olfactory receptors (ORs) in olfactory receptor neurons (ORNs). These ORs have a dynamic odorant detection range and contribute to signal encoding processes in the olfactory bulb (OB). To harness the capabilities of the olfactory system and develop a biomimetic sensor, stable culture and maintenance of ORNs are required. However, in vitro monolayer culture models have several key limitations: i) short available period of cultured neurons, ii) low cultural efficiency, and iii) long-term storage challenges. This study aims to develop a technique: i) to support the spheroid culture of primary ORN precursors facilitating stable maintenance and long-term storage, and ii) to demonstrate the viability of ORN spheroid culture in developing an olfactory system mimetic bioelectronic nose. Recombinant protein (REP; TGPG[VGRGD(VGVPG)₆]₂₀WPC) was used to form the ORN spheroids. Spheroid formation enabled preservation of primary cultured ORNs without a significant decrease in viability or the expression of stemness markers for ten days. Physiological characteristics of the ORNs were verified by monitoring intracellular calcium concentration upon odorant mixture stimulation; response upon odorant stimulation were observed at least for ten days in these cultivated ORNs differentiated from spheroids. Coupling ORNs with multi electrode array (MEA) enabled the detection and discrimination of odorants by analyzing the electrical signal patterns generated following odorant stimulation. Taken together, the ORN spheroid culture process is a promising technique for the development of a bioelectronic nose and high-throughput odorant screening device.
Biomimetics ; Calcium ; Discrimination (Psychology) ; Electrodes ; In Vitro Techniques ; Mass Screening ; Neurons ; Nose* ; Odors ; Olfactory Bulb ; Olfactory Receptor Neurons*