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Dynamic Impairment of Olfactory Behavior and Signaling Mediated by an Olfactory Corticofugal System.The Journal of Neuroscience : the... Sep 2020Processing of olfactory information is modulated by centrifugal projections from cortical areas, yet their behavioral relevance and underlying neural mechanisms remain...
Processing of olfactory information is modulated by centrifugal projections from cortical areas, yet their behavioral relevance and underlying neural mechanisms remain unclear in most cases. The anterior olfactory nucleus (AON) is part of the olfactory cortex, and its extensive connections to multiple upstream and downstream brain centers place it in a prime position to modulate early sensory information in the olfactory system. Here, we show that optogenetic activation of AON neurons in awake male and female mice was not perceived as an odorant equivalent cue. However, AON activation during odorant presentation reliably suppressed behavioral odor responses. This AON-mediated effect was fast and constant across odors and concentrations. Likewise, activation of glutamatergic AON projections to the olfactory bulb (OB) transiently inhibited the excitability of mitral/tufted cells (MTCs) that relay olfactory input to the cortex. Single-unit MTC recordings revealed that optogenetic activation of glutamatergic AON terminals in the OB transiently decreased sensory-evoked MTC spiking, regardless of the strength or polarity of the sensory response. The reduction in MTC firing during optogenetic stimulation was confirmed in recordings in awake mice. These findings suggest that glutamatergic AON projections to the OB impede early olfactory signaling by inhibiting OB output neurons, thereby dynamically gating sensory throughput to the cortex. The anterior olfactory nucleus (AON) as an olfactory information processing area sends extensive projections to multiple brain centers, but the behavioral consequences of its activation have been scarcely investigated. Using behavioral tests in combination with optogenetic manipulation, we show that, in contrast to what has been suggested previously, the AON does not seem to form odor percepts but instead suppresses behavioral odor responses across odorants and concentrations. Furthermore, this study shows that AON activation inhibits olfactory bulb output neurons in both anesthetized as well as awake mice, pointing to a potential mechanism by which the olfactory cortex can actively and dynamically gate sensory throughput to higher brain centers.
Topics: Animals; Female; Glutamic Acid; Male; Mice; Mice, Inbred C57BL; Neurons, Afferent; Olfactory Bulb; Olfactory Pathways; Olfactory Perception; Smell; Synaptic Transmission
PubMed: 32817250
DOI: 10.1523/JNEUROSCI.2667-19.2020 -
European Archives of... Mar 2022To evaluate the success of olfactory training in patients with olfactory loss and olfactory bulb (OB) atrophy detected on magnetic resonance imaging (MRI) and other...
PURPOSE
To evaluate the success of olfactory training in patients with olfactory loss and olfactory bulb (OB) atrophy detected on magnetic resonance imaging (MRI) and other characteristics.
METHODS
This study included 48 patients with olfactory loss who underwent a nasal endoscopic examination and MRI before olfactory training. The Korean Version of the Sniffin' Sticks Test was performed before and after training. The olfactory training success was defined as an improvement of more than 6 points in the Threshold-Discrimination-Identification (TDI) score. Patient characteristics and OB atrophy pre-training were compared between successful and unsuccessful groups.
RESULTS
The etiology of olfactory loss included respiratory viral infection in 30 (62.5%), trauma in 10 (20.8%), and idiopathic loss in 8 (16.7%) patients. Twenty-three (47.9%) of 48 patients exhibited successful olfactory training. Etiology, age, gender, and symptom duration were not different between unsuccessful and successful groups. Pre-training discrimination, identification, and TDI scores were significantly different between unsuccessful and successful groups (P < 0.05). Success rate of patients with bilateral OB atrophy was significantly lower than that of patients with unilateral OB atrophy and normal morphology (P = 0.006). OB height was significantly lower in the unsuccessful group than in the successful group (P < 0.05). Bilateral OB atrophy was an independent risk factor for failure of olfactory training according to the multivariate analysis.
CONCLUSION
Olfactory loss patients with bilateral OB atrophy may not be able to improve olfactory function after olfactory training.
Topics: Atrophy; Humans; Magnetic Resonance Imaging; Olfaction Disorders; Olfactory Bulb; Smell
PubMed: 34091728
DOI: 10.1007/s00405-021-06917-z -
Frontiers in Neural Circuits 2020Generation of neuronal diversity is a biological strategy widely used in the brain to process complex information. The olfactory bulb is the first relay station of... (Review)
Review
Generation of neuronal diversity is a biological strategy widely used in the brain to process complex information. The olfactory bulb is the first relay station of olfactory information in the vertebrate central nervous system. In the olfactory bulb, axons of the olfactory sensory neurons form synapses with dendrites of projection neurons that transmit the olfactory information to the olfactory cortex. Historically, the olfactory bulb projection neurons have been classified into two populations, mitral cells and tufted cells. The somata of these cells are distinctly segregated within the layers of the olfactory bulb; the mitral cells are located in the mitral cell layer while the tufted cells are found in the external plexiform layer. Although mitral and tufted cells share many morphological, biophysical, and molecular characteristics, they differ in soma size, projection patterns of their dendrites and axons, and odor responses. In addition, tufted cells are further subclassified based on the relative depth of their somata location in the external plexiform layer. Evidence suggests that different types of tufted cells have distinct cellular properties and play different roles in olfactory information processing. Therefore, mitral and different types of tufted cells are considered as starting points for parallel pathways of olfactory information processing in the brain. Moreover, recent studies suggest that mitral cells also consist of heterogeneous subpopulations with different cellular properties despite the fact that the mitral cell layer is a single-cell layer. In this review, we first compare the morphology of projection neurons in the olfactory bulb of different vertebrate species. Next, we explore the similarities and differences among subpopulations of projection neurons in the rodent olfactory bulb. We also discuss the timing of neurogenesis as a factor for the generation of projection neuron heterogeneity in the olfactory bulb. Knowledge about the subpopulations of olfactory bulb projection neurons will contribute to a better understanding of the complex olfactory information processing in higher brain regions.
Topics: Animals; Dendrites; Humans; Interneurons; Neurons; Olfactory Bulb; Olfactory Pathways; Olfactory Receptor Neurons; Synapses
PubMed: 32982699
DOI: 10.3389/fncir.2020.561822 -
Cell and Tissue Research Jan 2021Whether an odorant is perceived as pleasant or unpleasant (hedonic value) governs a range of crucial behaviors: foraging, escaping danger, and social interaction.... (Review)
Review
Whether an odorant is perceived as pleasant or unpleasant (hedonic value) governs a range of crucial behaviors: foraging, escaping danger, and social interaction. Despite its importance in olfactory perception, little is known regarding how odor hedonics is represented and encoded in the brain. Here, we review recent findings describing how odorant hedonic value is represented in the first olfaction processing center, the olfactory bulb. We discuss how olfactory bulb circuits might contribute to the coding of innate and learned odorant hedonics in addition to the odorant's physicochemical properties.
Topics: Animals; Odorants; Olfactory Bulb; Vertebrates
PubMed: 33515292
DOI: 10.1007/s00441-020-03372-w -
The Journal of Neuroscience : the... Jul 2022Metabolic state can alter olfactory sensitivity, but it is unknown whether the activity of the olfactory bulb (OB) may fine tune metabolic homeostasis. Our objective was...
Metabolic state can alter olfactory sensitivity, but it is unknown whether the activity of the olfactory bulb (OB) may fine tune metabolic homeostasis. Our objective was to use CRISPR gene editing in male and female mice to enhance the excitability of mitral/tufted projection neurons (M/TCs) of the OB to test for improved metabolic health. slice recordings of MCs in CRISPR mice confirmed increased excitability due the targeted loss of Kv1.3 channels, which resulted in a less negative resting membrane potential (RMP), enhanced action potential (AP) firing, and insensitivity to the selective channel blocker margatoxin (MgTx). CRISPR mice exhibited enhanced odor discrimination using a habituation/dishabituation paradigm. CRISPR mice were challenged for 25 weeks with a moderately high-fat (MHF) diet, and compared with littermate controls, male mice were resistance to diet-induced obesity (DIO). Female mice did not exhibit DIO. CRISPR male mice gained less body weight, accumulated less white adipose tissue, cleared a glucose challenge more quickly, and had less serum leptin and liver triglycerides. CRISPR male mice consumed equivalent calories as control littermates, and had unaltered energy expenditure (EE) and locomotor activity, but used more fats for metabolic substrate over that of carbohydrates. Counter to CRISPR-engineered mice, by using chemogenetics to decrease M/TC excitability in male mice, activation of inhibitory designer receptors exclusively activated by designer drugs (DREADDs) caused a decrease in odor discrimination, and resulted in a metabolic profile that was obesogenic, mice had reduced EE and oxygen consumption (VO). We conclude that the activity of M/TC projection neurons canonically carries olfactory information and simultaneously can regulate whole-body metabolism. The olfactory system drives food choice, and olfactory sensitivity is strongly correlated to hunger and fullness. Olfactory function thereby influences nutritional balance and obesity outcomes. Obesity has become a health and financial crisis in America, shortening life expectancy and increasing the severity of associated illnesses. It is expected that 51% of Americans will be obese by the year 2030. Using CRISPR gene editing and chemogenetic approaches, we discovered that changing the excitability of output neurons in the olfactory bulb (OB) affects metabolism and body weight stabilization in mice. Our results suggest that long-term therapeutic targeting of OB activity to higher processing centers may be a future clinical treatment of obesity or type II Diabetes.
Topics: Animals; Body Weight; Diabetes Mellitus, Type 2; Diet, High-Fat; Female; Humans; Male; Mice; Mice, Inbred C57BL; Neurons; Obesity; Olfactory Bulb
PubMed: 35710623
DOI: 10.1523/JNEUROSCI.0190-22.2022 -
Cell and Tissue Research Jan 2021The necklace glomeruli are a loosely defined group of glomeruli encircling the caudal main olfactory bulb in rodents. Initially defined by the expression of various... (Review)
Review
The necklace glomeruli are a loosely defined group of glomeruli encircling the caudal main olfactory bulb in rodents. Initially defined by the expression of various immunohistochemical markers, they are now better understood in the context of the specialized chemosensory neurons of the main olfactory epithelium and Grueneberg ganglion that innervate them. It has become clear that the necklace region of the rodent main olfactory bulb is composed of multiple distinct groups of glomeruli, defined at least in part by their afferent inputs. In this review, we will explore the necklace glomeruli and the chemosensory neurons that innervate them.
Topics: Animals; Olfactory Bulb; Olfactory Pathways; Rodentia
PubMed: 33404845
DOI: 10.1007/s00441-020-03388-2 -
Surgical and Radiologic Anatomy : SRA Sep 2020The aim of this study was to evaluate olfactory bulbus volume (OBV) and olfactory sulcus depth (OSD) according to age and sex with 3 T MRI in a healthy Turkish...
OBJECTIVE
The aim of this study was to evaluate olfactory bulbus volume (OBV) and olfactory sulcus depth (OSD) according to age and sex with 3 T MRI in a healthy Turkish population.
MATERIALS AND METHODS
In the current study, 200 patients who had cranial MRI were retrospectively evaluated. They were divided into the following groups to examine the effects of age: group 1: 18-30 years old; group 2: 31-40 years old; group 3: 41-50 years old; group 4: 51-60 years old; and group 5: >60 years old. OBV and OSD measurements were performed on coronal T2-weighted brain MR images. The mean right and left olfactory bulb volume and sulcus depths were used for evaluation.
RESULTS
The mean age was 46.5 ± 18.1 (range 18-86) years. The mean OBV value of both sides was 91.17 ± 7.8 mm 3 in all patients. The mean OSD value of both sides was 8.62 ± 0.84 mm in all patients. There was no statistically significant difference in OBV and OSD between sexes (P < 0.236; P < 0.482). Group 5 (>60 years old) was found to have significantly lower OBV and OSD values than the other groups (all P < 0.001).
CONCLUSION
The normal values of OBV and OSD should be established according to age to determine decreased OBV and OSD values.
Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Anatomic Variation; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Olfaction Disorders; Olfactory Bulb; Organ Size; Prefrontal Cortex; Reference Values; Retrospective Studies; Young Adult
PubMed: 32377954
DOI: 10.1007/s00276-020-02484-w -
Current Biology : CB Nov 2023The olfactory bulb (OB) is a critical component of mammalian olfactory neuroanatomy. Beyond being the first and sole relay station for olfactory information to the rest...
The olfactory bulb (OB) is a critical component of mammalian olfactory neuroanatomy. Beyond being the first and sole relay station for olfactory information to the rest of the brain, it also contains elaborate stereotypical circuitry that is considered essential for olfaction. Indeed, substantial lesions of the OB in rodents lead to anosmia. Here, we examined the circuitry that underlies olfaction in a mouse model with severe developmental degeneration of the OB. These mice could perform odor-guided tasks and even responded normally to innate olfactory cues. Despite the near total loss of the OB, piriform cortices in these mice responded to odors, and its neural activity sufficed to decode odor identity. We found that sensory neurons express the full repertoire of olfactory receptors, and their axons project primarily to the rudiments of the OB but also, ectopically, to olfactory cortical regions. Within the OB, the number of principal neurons was greatly reduced, and the morphology of their dendrites was abnormal, extending over large regions within the OB. Glomerular organization was totally lost in the severe cases of OB degeneration and altered in the more conserved OBs. This study shows that olfactory functionality can be preserved despite reduced and aberrant circuitry that is missing many of the elements believed to be essential for olfaction, and it may explain reported retention of olfaction in humans with degenerated OBs.
Topics: Humans; Mice; Animals; Olfactory Bulb; Smell; Olfactory Receptor Neurons; Odorants; Axons; Mammals
PubMed: 37858342
DOI: 10.1016/j.cub.2023.09.061 -
Ageing Research Reviews Jun 2024Parkinson's disease (PD) is a prevalent neurodegenerative disorder that affects 7-10 million individuals worldwide. A common early symptom of PD is olfactory dysfunction... (Review)
Review
Parkinson's disease (PD) is a prevalent neurodegenerative disorder that affects 7-10 million individuals worldwide. A common early symptom of PD is olfactory dysfunction (OD), and more than 90% of PD patients suffer from OD. Recent studies have highlighted a high incidence of OD in patients with SARS-CoV-2 infection. This review investigates the potential convergence of OD in PD and COVID-19, particularly focusing on the mechanisms by which neuroinflammation contributes to OD and neurological events. Starting from our fundamental understanding of the olfactory bulb, we summarize the clinical features of OD and pathological features of the olfactory bulb from clinical cases and autopsy reports in PD patients. We then examine SARS-CoV-2-induced olfactory bulb neuropathology and OD and emphasize the SARS-CoV-2-induced neuroinflammatory cascades potentially leading to PD manifestations. By activating microglia and astrocytes, as well as facilitating the aggregation of α-synuclein, SARS-CoV-2 could contribute to the onset or exacerbation of PD. We also discuss the possible contributions of NF-κB, the NLRP3 inflammasome, and the JAK/STAT, p38 MAPK, TLR4, IL-6/JAK2/STAT3 and cGAS-STING signaling pathways. Although olfactory dysfunction in patients with COVID-19 may be reversible, it is challenging to restore OD in patients with PD. With the emergence of new SARS-CoV-2 variants and the recurrence of infections, we call for continued attention to the intersection between PD and SARS-CoV-2 infection, especially from the perspective of OD.
Topics: Humans; COVID-19; Parkinson Disease; Neuroinflammatory Diseases; Olfaction Disorders; SARS-CoV-2; Olfactory Bulb
PubMed: 38580172
DOI: 10.1016/j.arr.2024.102288 -
Brazilian Journal of Otorhinolaryngology 2020Olfactory ensheathing cell is a unique kind of glia cells, which can promote axon growth. Little is known about the differences between olfactory mucosa olfactory...
INTRODUCTION
Olfactory ensheathing cell is a unique kind of glia cells, which can promote axon growth. Little is known about the differences between olfactory mucosa olfactory ensheathing cells and olfactory bulb olfactory ensheathing cells in the capability to promote nerve regeneration.
OBJECTIVE
To study the recovery of the rat facial nerve after olfactory ensheathing cells transplantation, and to compare the differences between the facial nerve regeneration of olfactory mucosa-olfactory ensheathing cells and olfactory bulb olfactory bulb olfactory ensheathing cells transplantation.
METHODS
Institutional ethical guideline was followed (201510129A). Olfactory mucosa-olfactory ensheathing cells and olfactory bulb olfactory ensheathing cells were cultured and harvested after 7 days in vitro. 36 Sprague Dawley male rats were randomly divided into three different groups depending on the transplanting cells: Group A: olfactory mucosa-olfactory ensheathing cells; Group B: olfactory bulb olfactory ensheathing cells; Group C: DF-12 medium/fetal bovine serum. The main trunk of the facial nerve was transected and both stumps were inserted into a polylactic acid/chitosan conduit, then the transplanted cells were injected into the collagen in the conduits. After 4 and 8 weeks after the transplant, the rats of the three groups were scarified and the facial function score, facial nerve evoked potentials, histology analysis, and fluorescent retrograde tracing were tested and recorded, respectively, to evaluate the facial nerve regeneration and to analysis the differences among the three groups.
RESULTS
Olfactory ensheathing cells can promote the facial nerve regeneration. Compared with olfactory bulb olfactory ensheathing cells, olfactory mucosa olfactory ensheathing cells were more effective in promoting facial nerve regeneration, and this difference was more significant 8 weeks after the transplantation than 4 weeks.
CONCLUSION
We discovered that olfactory ensheathing cells with nerve conduit could improve the facial nerve recovery, and the olfactory mucosa olfactory ensheathing cells are more effective for facial nerve regeneration compared with olfactory bulb olfactory ensheathing cells 8 weeks after the transplantation. These results could cast new light in the therapy of facial nerve defect, and furnish the foundation of auto-transplantation of olfactory mucosa olfactory ensheathing cells in periphery nerve injury.
Topics: Animals; Facial Nerve; Male; Nerve Regeneration; Olfactory Bulb; Olfactory Mucosa; Rats; Rats, Sprague-Dawley
PubMed: 30497873
DOI: 10.1016/j.bjorl.2018.07.006