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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 -
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 -
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 -
Brain Research Jun 2024Immune-inflammatory response is a key element in the occurrence and development of olfactory dysfunction (OD) in patients with allergic rhinitis (AR). As one of the core...
BACKGROUND
Immune-inflammatory response is a key element in the occurrence and development of olfactory dysfunction (OD) in patients with allergic rhinitis (AR). As one of the core factors in immune-inflammatory responses, interleukin (IL)-6 is closely related to the pathogenesis of allergic diseases. It may also play an important role in OD induced by diseases, such as Sjögren's syndrome and coronavirus disease 2019. However, there is no study has reported its role in OD in AR. Thus, this study aimed to investigate the role of IL-6 in AR-related OD, in an attempt to discover a new target for the prevention and treatment of OD in patients with AR.
METHODS
Differential expression analysis was performed using the public datasets GSE52804 and GSE140454 for AR, and differentially expressed genes (DEGs) were obtained by obtaining the intersection points between these two datasets. IL-6, a common differential factor, was obtained by intersecting the DEGs with the General Olfactory Sensitivity Database (GOSdb) again. A model of AR mice with OD was developed by sensitizing with ovalbumin (OVA) to verify the reliability of IL-6 as a key factor of OD in AR and explore the potential mechanisms. Furthermore, a supernatant and microglia co-culture model of nasal mucosa epithelial cells stimulated by the allergen house dust mite extract Derp1 was established to identify the cellular and molecular mechanisms of IL-6-mediated OD in AR.
RESULTS
The level of IL-6 in the nasal mucosa and olfactory bulb of AR mice with OD significantly increased and showed a positive correlation with the expression of olfactory bulb microglia marker Iba-1 and the severity of OD. In-vitro experiments showed that the level of IL-6 significantly increased in the supernatant after the nasal mucosa epithelial cells were stimulated by Derp1, along with significantly decreased barrier function of the nasal mucosa. The expression levels of neuroinflammatory markers IL-1β and INOS increased after a conditioned culture of microglia with the supernatant including IL-6. Then knockdown (KD) of IL-6R by small interfering RNA (siRNA), the expression of IL-1β and INOS significantly diminished.
CONCLUSION
IL-6 plays a key role in the occurrence and development of OD in AR, which may be related to its effect on olfactory bulb microglia-mediated neuroinflammation.
Topics: Animals; Mice; Disease Models, Animal; Interleukin-6; Microglia; Olfaction Disorders; Olfactory Bulb; Ovalbumin; Rhinitis, Allergic; Male; Mice, Inbred C57BL
PubMed: 38531465
DOI: 10.1016/j.brainres.2024.148885 -
Academic Radiology Jan 2021There is limited literature consisting of case reports or series on olfactory bulb imaging in COVID-19 olfactory dysfunction. An imaging study with objective clinical...
BACKGROUND AND PURPOSE
There is limited literature consisting of case reports or series on olfactory bulb imaging in COVID-19 olfactory dysfunction. An imaging study with objective clinical correlation is needed in COVID-19 anosmia in order to better understand underlying pathogenesis.
MATERIAL AND METHODS
We evaluated 23 patients with persistent COVID-19 olfactory dysfunction. Patients included in this study had a minimum 1-month duration between onset of olfactory dysfunction and evaluation. Olfactory functions were evaluated with Sniffin' Sticks Test. Paranasal sinus CTs and MRI dedicated to olfactory nerves were acquired. On MRI, quantitative measurements of olfactory bulb volumes and olfactory sulcus depth and qualitative assessment of olfactory bulb morphology, signal intensity, and olfactory nerve filia architecture were performed.
RESULTS
All patients were anosmic at the time of imaging based on olfactory test results. On CT, Olfactory cleft opacification was seen in 73.9% of cases with a mid and posterior segment dominance. 43.5% of cases had below normal olfactory bulb volumes and 60.9% of cases had shallow olfactory sulci. Of all, 54.2% of cases had changes in normal inverted J shape of the bulb. 91.3% of cases had abnormality in olfactory bulb signal intensity in the forms of diffusely increased signal intensity, scattered hyperintense foci or microhemorrhages. Evident clumping of olfactory filia was seen in 34.8% of cases and thinning with scarcity of filia in 17.4%. Primary olfactory cortical signal abnormality was seen in 21.7% of cases.
CONCLUSION
Our findings indicate olfactory cleft and olfactory bulb abnormalities are seen in COVID-19 anosmia. There was a relatively high percentage of olfactory bulb degeneration. Further longitudinal imaging studies could shed light on the mechanism of olfactory neuronal pathway injury in COVID-19 anosmia.
Topics: Anosmia; COVID-19; Humans; Magnetic Resonance Imaging; Olfaction Disorders; Olfactory Bulb; Pandemics; SARS-CoV-2; Tomography, X-Ray Computed
PubMed: 33132007
DOI: 10.1016/j.acra.2020.10.006 -
Communications Biology Sep 2022The olfactory nerve map describes the topographical neural connections between the olfactory epithelium in the nasal cavity and the olfactory bulb. Previous studies have...
The olfactory nerve map describes the topographical neural connections between the olfactory epithelium in the nasal cavity and the olfactory bulb. Previous studies have constructed the olfactory nerve maps of rodents using histological analyses or transgenic animal models to investigate olfactory nerve pathways. However, the human olfactory nerve map remains unknown. Here, we demonstrate that high-field magnetic resonance imaging and diffusion tensor tractography can be used to visualize olfactory sensory neurons while maintaining their three-dimensional structures. This technique allowed us to evaluate the olfactory sensory neuron projections from the nasal cavities to the olfactory bulbs and visualize the olfactory nerve maps of humans, marmosets and mice. The olfactory nerve maps revealed that the dorsal-ventral and medial-lateral axes were preserved between the olfactory epithelium and olfactory bulb in all three species. Further development of this technique might allow it to be used clinically to facilitate the diagnosis of olfactory dysfunction.
Topics: Animals; Humans; Magnetic Resonance Imaging; Mice; Olfactory Bulb; Olfactory Mucosa; Olfactory Nerve; Olfactory Pathways
PubMed: 36068329
DOI: 10.1038/s42003-022-03794-y -
Nature Mar 2022Neuroanatomists have long speculated that expanded primate brains contain an increased morphological diversity of inhibitory neurons (INs), and recent studies have...
Neuroanatomists have long speculated that expanded primate brains contain an increased morphological diversity of inhibitory neurons (INs), and recent studies have identified primate-specific neuronal populations at the molecular level. However, we know little about the developmental mechanisms that specify evolutionarily novel cell types in the brain. Here, we reconstruct gene expression trajectories specifying INs generated throughout the neurogenic period in macaques and mice by analysing the transcriptomes of 250,181 cells. We find that the initial classes of INs generated prenatally are largely conserved among mammals. Nonetheless, we identify two contrasting developmental mechanisms for specifying evolutionarily novel cell types during prenatal development. First, we show that recently identified primate-specific TAC3 striatal INs are specified by a unique transcriptional programme in progenitors followed by induction of a distinct suite of neuropeptides and neurotransmitter receptors in new-born neurons. Second, we find that multiple classes of transcriptionally conserved olfactory bulb (OB)-bound precursors are redirected to expanded primate white matter and striatum. These classes include a novel peristriatal class of striatum laureatum neurons that resemble dopaminergic periglomerular cells of the OB. We propose an evolutionary model in which conserved initial classes of neurons supplying the smaller primate OB are reused in the enlarged striatum and cortex. Together, our results provide a unified developmental taxonomy of initial classes of mammalian INs and reveal multiple developmental mechanisms for neural cell type evolution.
Topics: Animals; Biological Evolution; Corpus Striatum; Dopaminergic Neurons; Embryonic Development; Female; Macaca; Mammals; Mice; Neurogenesis; Neurons; Olfactory Bulb; Pregnancy; Primates
PubMed: 35322231
DOI: 10.1038/s41586-022-04510-w