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Physiology & Behavior Jun 2023Allergic rhinitis (AR) has been identified as a cause of olfactory dysfunction. Beyond the classic symptoms, AR has been associated with altered sleep patterns, a...
BACKGROUND
Allergic rhinitis (AR) has been identified as a cause of olfactory dysfunction. Beyond the classic symptoms, AR has been associated with altered sleep patterns, a decline in cognitive performance and higher likelihood of depression and anxiety. The olfactory pathway has been postulated to be a possible link between nasal inflammation and central nervous system (CNS) modifications. Thus, we aimed to investigate the structural, functional and behavioral changes in the olfactory pathway and related areas in an animal model of AR.
METHODS
AR was induced in adult Wistar rats by ovalbumin sensitization and challenge. Following olfactory and behavioral tests we investigated the synaptic structure of the olfactory bulb (OB), anterior olfactory nuclei (AON), piriform cortex and prefrontal cortex (PFC), by immunofluorescence detection of synaptophysin (Syn) and glutamatergic, GABAergic and dopaminergic neuronal markers.
RESULTS
We detected a significant decrease in Syn in the glomerular layer (GL) of OB and in the PFC of the AR group. Additionally, the optical density of GAD67 and VGLUT2 was reduced in the OB, AON and PFC, compared to controls. The behavioral tests demonstrated olfactory dysfunction and reduced male aggressiveness in AR rats, but we did not find any difference in the cognition and anxiety-like behavior.
CONCLUSIONS
We confirmed olfactory dysfunction in a rat model of AR and we identified modifications in synaptic activity by reduction of Syn optical density in the GL of the OB and in the PFC. This was accompanied by structural changes in glutamatergic and GABAergic activity in essential components of the olfactory pathway and PFC.
Topics: Rats; Male; Animals; Olfactory Pathways; Rats, Wistar; Olfactory Bulb; Prefrontal Cortex; Rhinitis, Allergic; Olfaction Disorders
PubMed: 36965572
DOI: 10.1016/j.physbeh.2023.114171 -
Molecules and Cells Mar 2020The olfactory bulb (OB) has an extremely higher proportionof interneurons innervating excitatory neurons than otherbrain regions, which is evolutionally conserved across... (Review)
Review
The olfactory bulb (OB) has an extremely higher proportionof interneurons innervating excitatory neurons than otherbrain regions, which is evolutionally conserved across species.Despite the abundance of OB interneurons, little is knownabout the diversification and physiological functions ofOB interneurons compared to cortical interneurons. In thisreview, an overview of the general developmental processof interneurons from the angles of the spatial and temporalspecifications was presented. Then, the distinct featuresshown exclusively in OB interneurons development andmolecular machinery recently identified were discussed.Finally, we proposed an evolutionary meaning for thediversity of OB interneurons.
Topics: Humans; Interneurons; Olfactory Bulb
PubMed: 32208366
DOI: 10.14348/molcells.2020.0033 -
Cell Transplantation 2022Olfactory ensheathing cell (OEC) transplantation is emerging as a promising treatment option for injuries of the nervous system. OECs can be obtained relatively easily... (Review)
Review
Olfactory ensheathing cell (OEC) transplantation is emerging as a promising treatment option for injuries of the nervous system. OECs can be obtained relatively easily from nasal biopsies, and exhibit several properties such as secretion of trophic factors, and phagocytosis of debris that facilitate neural regeneration and repair. But a major limitation of OEC-based cell therapies is the poor survival of transplanted cells which subsequently limit their therapeutic efficacy. There is an unmet need for approaches that enable the production of OECs in a state that will optimize their survival and integration after transplantation into the hostile injury site. Here, we present an overview of the strategies to modulate OECs focusing on oxygen levels, stimulating migratory, phagocytic, and secretory properties, and on bioengineering a suitable environment .
Topics: Cell Transplantation; Cellular Microenvironment; Neuroglia; Olfactory Bulb; Oxygen
PubMed: 36124646
DOI: 10.1177/09636897221125685 -
ENeuro 2021Bilateral convergence of external stimuli is a common feature of vertebrate sensory systems. This convergence of inputs from the bilateral receptive fields allows higher...
Bilateral convergence of external stimuli is a common feature of vertebrate sensory systems. This convergence of inputs from the bilateral receptive fields allows higher order sensory perception, such as depth perception in the vertebrate visual system and stimulus localization in the auditory system. The functional role of such bilateral convergence in the olfactory system is unknown. To test whether each olfactory bulb (OB) contributes a separate piece of olfactory information, and whether information from the bilateral OB is integrated, we synchronized the activation of OBs with blue light in mice expressing ChIEF in the olfactory sensory neurons (OSNs) and behaviorally assessed the relevance of dual OBs in olfactory perception. Our findings suggest that each OB contributes separate components of olfactory information, and the mice integrate the bilaterally synchronized olfactory information for olfactory identity.
Topics: Animals; Light; Mice; Olfactory Bulb; Olfactory Perception; Olfactory Receptor Neurons; Smell
PubMed: 34413085
DOI: 10.1523/ENEURO.0070-21.2021 -
Toxicologic Pathology Apr 2022With advances in nanotechnology, engineered nanomaterial applications are a rapidly growing sector of the economy. Some nanomaterials can reach the brain through...
With advances in nanotechnology, engineered nanomaterial applications are a rapidly growing sector of the economy. Some nanomaterials can reach the brain through nose-to-brain transport. This transport creates concern for potential neurotoxicity of insoluble nanomaterials and a need for toxicity screening tests that detect nose-to-brain transport. Such tests can involve intranasal instillation of aqueous suspensions of nanomaterials in dispersion media that limit particle agglomeration. Unfortunately, protein and some elements in existing dispersion media are suboptimal for potential nose-to-brain transport of nanomaterials because olfactory transport has size- and ion-composition requirements. Therefore, we designed a protein-free dispersion media containing phospholipids and amino acids in an isotonic balanced electrolyte solution, a solution for nasal and olfactory transport (SNOT). SNOT disperses hexagonal boron nitride nanomaterials with a peak particle diameter below 100 nm. In addition, multiwalled carbon nanotubes (MWCNTs) in an established dispersion medium, when diluted with SNOT, maintain dispersion with reduced albumin concentration. Using stereomicroscopy and microscopic examination of plastic sections, dextran dyes dispersed in SNOT are demonstrated in the neuroepithelium of the nose and olfactory bulb of B6;129P2-MomJ mice after intranasal instillation in SNOT. These findings support the potential for SNOT to disperse nanomaterials in a manner permitting nose-to-brain transport for neurotoxicity studies.
Topics: Administration, Intranasal; Animals; Brain; Mice; Nanostructures; Nanotubes, Carbon; Olfactory Bulb; Toxicity Tests
PubMed: 35416103
DOI: 10.1177/01926233221089209 -
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 -
Cell and Tissue Research Jan 2023Sex steroid hormones influence olfactory-mediated social behaviors, and it is generally hypothesized that these effects result from circulating hormones and/or... (Review)
Review
Sex steroid hormones influence olfactory-mediated social behaviors, and it is generally hypothesized that these effects result from circulating hormones and/or neurosteroids synthesized in the brain. However, it is unclear whether sex steroid hormones are synthesized in the olfactory epithelium or the olfactory bulb, and if they can modulate the activity of the olfactory sensory neurons. Here, we review important discoveries related to the metabolism of sex steroids in the mouse olfactory epithelium and olfactory bulb, along with potential areas of future research. We summarize current knowledge regarding the expression, neuroanatomical distribution, and biological activity of the steroidogenic enzymes, sex steroid receptors, and proteins that are important to the metabolism of these hormones and reflect on their potential to influence early olfactory processing. We also review evidence related to the effects of sex steroid hormones on the development and activity of olfactory sensory neurons. By better understanding how these hormones are metabolized and how they act both at the periphery and olfactory bulb level, we can better appreciate the complexity of the olfactory system and discover potential similarities and differences in early olfactory processing between sexes.
Topics: Mice; Animals; Gonadal Steroid Hormones; Hormones; Olfactory Receptor Neurons; Olfactory Mucosa; Olfactory Bulb; Proteins; Mammals
PubMed: 36401093
DOI: 10.1007/s00441-022-03707-9 -
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