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AJNR. American Journal of Neuroradiology Apr 2020The olfactory bulbs and tracts are central nervous system white matter tracts maintained by central neuroglia. Although rare, gliomas can originate from and progress to...
The olfactory bulbs and tracts are central nervous system white matter tracts maintained by central neuroglia. Although rare, gliomas can originate from and progress to involve the olfactory apparatus. Through a Health Insurance Portability and Accountability Act-compliant retrospective review of the institutional teaching files and brain MR imaging reports spanning 10 years, we identified 12 cases of gliomas involving the olfactory bulbs and tracts, including 6 cases of glioblastoma, 2 cases of anaplastic oligodendroglioma, and 1 case each of pilocytic astrocytoma, diffuse (grade II) astrocytoma, anaplastic astrocytoma (grade III), and diffuse midline glioma. All except the pilocytic astrocytoma occurred in patients with known primary glial tumors elsewhere. Imaging findings of olfactory tumor involvement ranged from well-demarcated enhancing masses to ill-defined enhancing infiltrative lesions to nonenhancing masslike FLAIR signal abnormality within the olfactory tracts. Familiarity with the imaging findings of glioma involvement of the olfactory nerves is important for timely diagnosis and treatment of recurrent gliomas and to distinguish them from other disease processes.
Topics: Adolescent; Adult; Aged; Brain Neoplasms; Child; Female; Glioma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Olfactory Bulb; Olfactory Pathways; Retrospective Studies
PubMed: 32165363
DOI: 10.3174/ajnr.A6471 -
Developmental Cell Jul 2023In developing brains, activity-dependent remodeling facilitates the formation of precise neuronal connectivity. Synaptic competition is known to facilitate synapse...
In developing brains, activity-dependent remodeling facilitates the formation of precise neuronal connectivity. Synaptic competition is known to facilitate synapse elimination; however, it has remained unknown how different synapses compete with one another within a post-synaptic cell. Here, we investigate how a mitral cell in the mouse olfactory bulb prunes all but one primary dendrite during the developmental remodeling process. We find that spontaneous activity generated within the olfactory bulb is essential. We show that strong glutamatergic inputs to one dendrite trigger branch-specific changes in RhoA activity to facilitate the pruning of the remaining dendrites: NMDAR-dependent local signals suppress RhoA to protect it from pruning; however, the subsequent neuronal depolarization induces neuron-wide activation of RhoA to prune non-protected dendrites. NMDAR-RhoA signals are also essential for the synaptic competition in the mouse barrel cortex. Our results demonstrate a general principle whereby activity-dependent lateral inhibition across synapses establishes a discrete receptive field of a neuron.
Topics: Dendrites; Olfactory Bulb; Synapses; Neurons; Cell Differentiation
PubMed: 37290446
DOI: 10.1016/j.devcel.2023.05.004 -
PloS One 2020For rodents, olfaction is essential for locating food, recognizing mates and competitors, avoiding predators, and navigating their environment. It is thought that...
For rodents, olfaction is essential for locating food, recognizing mates and competitors, avoiding predators, and navigating their environment. It is thought that rodents may have expanded olfactory receptor repertoires in order to specialize in olfactory behavior. Despite being the largest clade of mammals and depending on olfaction relatively little work has documented olfactory repertoires outside of conventional laboratory species. Here we report the olfactory receptor repertoire of the African giant pouched rat (Cricetomys ansorgei), a Muroid rodent distantly related to mice and rats. The African giant pouched rat is notable for its large cortex and olfactory bulbs relative to its body size compared to other sympatric rodents, which suggests anatomical elaboration of olfactory capabilities. We hypothesized that in addition to anatomical elaboration for olfaction, these pouched rats might also have an expanded olfactory receptor repertoire to enable their olfactory behavior. We examined the composition of the olfactory receptor repertoire to better understand how their sensory capabilities have evolved. We identified 1145 intact olfactory genes, and 260 additional pseudogenes within 301 subfamilies from the African giant pouched rat genome. This repertoire is similar to mice and rats in terms of size, pseudogene percentage and number of subfamilies. Analyses of olfactory receptor gene trees revealed that the pouched rat has 6 expansions in different subfamilies compared to mice, rats and squirrels. We identified 81 orthologous genes conserved among 4 rodent species and an additional 147 conserved genes within the Muroid rodents. The orthologous genes shared within Muroidea suggests that there may be a conserved Muroid-specific olfactory receptor repertoire. We also note that the description of this repertoire can serve as a complement to other studies of rodent olfaction, as the pouched rat is an outgroup within Muroidea. Thus, our data suggest that African giant pouched rats are capable of both natural and trained olfactory behaviors with a typical Muriod olfactory receptor repertoire.
Topics: Animals; Genome; Mice; Olfactory Bulb; Olfactory Receptor Neurons; Phylogeny; Pseudogenes; Rats; Receptors, Odorant; Smell
PubMed: 32240170
DOI: 10.1371/journal.pone.0221981 -
ELife Feb 2023Gamma oscillations are believed to underlie cognitive processes by shaping the formation of transient neuronal partnerships on a millisecond scale. These oscillations...
Gamma oscillations are believed to underlie cognitive processes by shaping the formation of transient neuronal partnerships on a millisecond scale. These oscillations are coupled to the phase of breathing cycles in several brain areas, possibly reflecting local computations driven by sensory inputs sampled at each breath. Here, we investigated the mechanisms and functions of gamma oscillations in the piriform (olfactory) cortex of awake mice to understand their dependence on breathing and how they relate to local spiking activity. Mechanistically, we find that respiration drives gamma oscillations in the piriform cortex, which correlate with local feedback inhibition and result from recurrent connections between local excitatory and inhibitory neuronal populations. Moreover, respiration-driven gamma oscillations are triggered by the activation of mitral/tufted cells in the olfactory bulb and are abolished during ketamine/xylazine anesthesia. Functionally, we demonstrate that they locally segregate neuronal assemblies through a winner-take-all computation leading to sparse odor coding during each breathing cycle. Our results shed new light on the mechanisms of gamma oscillations, bridging computation, cognition, and physiology.
Topics: Mice; Animals; Smell; Olfactory Bulb; Respiration; Odorants; Olfactory Cortex; Piriform Cortex
PubMed: 36806332
DOI: 10.7554/eLife.83044 -
Physiological Reports Nov 2019Odorant molecules stimulate olfactory receptor neurons, and axons of these neurons project into the main olfactory bulb where they synapse onto mitral and tufted cells....
Odorant molecules stimulate olfactory receptor neurons, and axons of these neurons project into the main olfactory bulb where they synapse onto mitral and tufted cells. These project to the primary olfactory cortex including the anterior olfactory nucleus (AON), the piriform cortex, amygdala, and the entorhinal cortex. The properties of mitral cells have been investigated extensively, but how odor information is processed in subsequent brain regions is less well known. In the present study, we recorded the electrical activity of AON neurons in anesthetized rats. Most AON cells fired in bursts of 2-10 spikes separated by very short intervals (<20 ms), in a period linked to the respiratory rhythm. Simultaneous recordings from adjacent neurons revealed that the rhythms of adjacent cells, while locked to the same underlying rhythm, showed marked differences in phase. We studied the responses of AON cells to brief high-frequency stimulation of the lateral olfactory tract, mimicking brief activation of mitral cells by odor. In different cells, such stimuli evoked transient or sustained bursts during stimulation or, more commonly, post-stimulation bursts after inhibition during stimulation. This suggests that, in AON cells, phase shifts occur as a result of post-inhibitory rebound firing, following inhibition by mitral cell input, and we discuss how this supports processing of odor information in the olfactory pathway. Cells were tested for their responsiveness to a social odor (the bedding of a strange male) among other simple and complex odors tested. In total, 11 cells responded strongly and repeatedly to bedding odor, and these responses were diverse, including excitation (transient or sustained), inhibition, and activation after odor presentation, indicating that AON neurons respond not only to the type of complex odor but also to temporal features of odor application.
Topics: Action Potentials; Animals; Electric Stimulation; Male; Odorants; Olfactory Bulb; Olfactory Cortex; Olfactory Receptor Neurons; Rats; Rats, Sprague-Dawley
PubMed: 31782263
DOI: 10.14814/phy2.14284 -
The Journal of Neuroscience : the... Feb 2022The axon initial segment (AIS), nodes of Ranvier, and the oligodendrocyte-derived myelin sheath have significant influence on the firing patterns of neurons and the...
The axon initial segment (AIS), nodes of Ranvier, and the oligodendrocyte-derived myelin sheath have significant influence on the firing patterns of neurons and the faithful, coordinated transmission of action potentials (APs) to downstream brain regions. In the olfactory bulb (OB), olfactory discrimination tasks lead to adaptive changes in cell firing patterns, and the output signals must reliably travel large distances to other brain regions along highly myelinated tracts. Whether myelinated axons adapt to facilitate olfactory sensory processing is unknown. Here, we investigate the morphology and physiology of mitral cell (MC) axons in the olfactory system of adult male and female mice and show that unilateral sensory deprivation causes system-wide adaptations in axonal morphology and myelin thickness. MC spiking patterns and APs also adapted to sensory deprivation. Strikingly, myelination and MC physiology were altered on both the deprived and nondeprived sides, indicating system level adaptations to reduced sensory input. Our work demonstrates a previously unstudied mechanism of plasticity in the olfactory system. Successful transmission of information from the olfactory bulb (OB) to piriform cortex through the lateral olfactory tract (LOT) relies on synchronized arrival of action potentials (APs). The coincident arrival of APs is dependent on reliable generation of APs in the axon initial segment (AIS) and fast conduction mediated by axon myelination. Here, we studied changes in mitral cell (MC) firing and AIS structure as well as changes in myelination of the LOT on unilateral olfactory deprivation in the adult mouse. Strikingly, myelination and MC physiology were altered on both the deprived and nondeprived sides, indicating system level adaptations to reduced sensory input. Our work demonstrates a previously unstudied mechanism of plasticity in the olfactory system.
Topics: Animals; Axons; Female; Male; Mice; Myelin Sheath; Olfactory Bulb; Sensory Deprivation; Smell
PubMed: 35022219
DOI: 10.1523/JNEUROSCI.0305-21.2021 -
Scientific Reports Jun 2023Depression is associated with reduced olfactory function. This relationship is assumed to be based on either a reduced olfactory bulb volume or diminished functioning of...
Depression is associated with reduced olfactory function. This relationship is assumed to be based on either a reduced olfactory bulb volume or diminished functioning of higher cortical areas. As previous results are controversial, we aimed to re-evaluate central olfactory processing in depression. We recorded the BOLD signal of 21 patients with Major Depressive Disorder and 21 age and gender matched healthy controls during odor presentation. In addition, we measured the individual olfactory bulb volume, tested odor identification and odor threshold, and asked for hedonic odor perception. In both groups, odor presentation led to a pronounced activation of primary olfactory areas. However, secondary olfactory areas were significantly less activated in depressed individuals. The two groups did not differ in olfactory bulb volume. Our results point towards altered olfactory processing in patients in those regions that relate to sensory integration and attention allocation. Difficulties in cognitive processing could impact olfactory function in depression. We are therefore in favor of a top-down mechanism originating in higher cortical areas explaining parts of the relation between depression and olfaction.
Topics: Humans; Depressive Disorder, Major; Smell; Odorants; Olfactory Bulb; Olfactory Cortex; Olfactory Perception
PubMed: 37344484
DOI: 10.1038/s41598-023-36783-0 -
Journal of Neurology Mar 2023Despite olfactory disorders being among the most common neurological complications of coronavirus disease 2019 (COVID-19), their pathogenesis has not been fully... (Observational Study)
Observational Study
BACKGROUND AND OBJECTIVE
Despite olfactory disorders being among the most common neurological complications of coronavirus disease 2019 (COVID-19), their pathogenesis has not been fully elucidated yet. Brain MR imaging is a consolidated method for evaluating olfactory system's morphological modification, but a few quantitative studies have been published so far. The aim of the study was to provide MRI evidence of olfactory system alterations in patients with COVID-19 and neurological symptoms, including olfactory dysfunction.
METHODS
196 COVID-19 patients (median age: 53 years, 56% females) and 39 controls (median age 55 years, 49% females) were included in this cross-sectional observational study; 78 of the patients reported olfactory loss as the only neurological symptom. MRI processing was performed by ad-hoc semi-automatic processing procedures. Olfactory bulb (OB) volume was measured on T2-weighted MRI based on manual tracing and normalized to the brain volume. Olfactory tract (OT) median signal intensity was quantified on fluid attenuated inversion recovery (FLAIR) sequences, after preliminary intensity normalization.
RESULTS
COVID-19 patients showed significantly lower left, right and total OB volumes than controls (p < 0.05). Age-related OB atrophy was found in the control but not in the patient population. No significant difference was found between patients with olfactory disorders and other neurological symptoms. Several outliers with abnormally high OT FLAIR signal intensity were found in the patient group.
CONCLUSIONS
Brain MRI findings demonstrated OB damage in COVID-19 patients with neurological complications. Future longitudinal studies are needed to clarify the transient or permanent nature of OB atrophy in COVID-19 pathology.
Topics: Female; Humans; Middle Aged; Male; COVID-19; Cross-Sectional Studies; Olfaction Disorders; Smell; Magnetic Resonance Imaging; Olfactory Bulb
PubMed: 36656356
DOI: 10.1007/s00415-023-11561-0 -
The Journal of Neuroscience : the... Nov 2023Fragile X syndrome (FXS) is the single most common monogenetic cause of autism spectrum disorders (ASDs) in humans. FXS is caused by loss of expression of the fragile X...
Fragile X syndrome (FXS) is the single most common monogenetic cause of autism spectrum disorders (ASDs) in humans. FXS is caused by loss of expression of the fragile X mental retardation protein (FMRP), an mRNA-binding protein encoded on the X chromosome involved in suppressing protein translation. Sensory processing deficits have been a major focus of studies of FXS in both humans and rodent models of FXS, but olfactory deficits remain poorly understood. Here, we conducted experiments in wild-type (WT) and knock-out (KO; ) mice (males) that lack expression of the gene encoding FMRP to assess olfactory circuit and behavioral abnormalities. In patch-clamp recordings conducted in slices of the olfactory bulb, output mitral cells (MCs) in KO mice displayed greatly enhanced excitation under baseline conditions, as evidenced by a much higher rate of occurrence of spontaneous network-level events known as long-lasting depolarizations (LLDs). The higher probability of spontaneous LLDs (sLLDs), which appeared to be because of a decrease in GABAergic synaptic inhibition in glomeruli leading to more feedforward excitation, caused a reduction in the reliability of stimulation-evoked responses in MCs. In addition, in a go/no-go operant discrimination paradigm, we found that KO mice displayed impaired discrimination of odors in difficult tasks that involved odor mixtures but not altered discrimination of monomolecular odors. We suggest that the KO-induced reduction in MC response reliability is one plausible mechanism for the impaired fine odor discrimination. Fragile X syndrome (FXS) in humans is associated with a range of debilitating deficits including aberrant sensory processing. One sensory system that has received comparatively little attention in studies in animal models of FXS is olfaction. Here, we report the first comprehensive physiological analysis of circuit defects in the olfactory bulb in the commonly-used knock-out (KO) mouse model of FXS. Our studies indicate that KO alters the local excitation/inhibition balance in the bulb, similar to what KO does in other brain circuits, but through a novel mechanism that involves enhanced feedforward excitation. Furthermore, KO mice display behavioral impairments in fine odor discrimination, an effect that may be explained by changes in neural response reliability.
Topics: Humans; Male; Animals; Mice; Olfactory Bulb; Fragile X Syndrome; Mice, Knockout; Odorants; Reproducibility of Results; Fragile X Mental Retardation Protein; Disease Models, Animal
PubMed: 37788940
DOI: 10.1523/JNEUROSCI.0584-23.2023 -
Nature Communications Jan 2020Current non-invasive neuroimaging methods can assess neural activity in all areas of the human brain but the olfactory bulb (OB). The OB has been suggested to fulfill a...
Current non-invasive neuroimaging methods can assess neural activity in all areas of the human brain but the olfactory bulb (OB). The OB has been suggested to fulfill a role comparable to that of V1 and the thalamus in the visual system and have been closely linked to a wide range of olfactory tasks and neuropathologies. Here we present a method for non-invasive recording of signals from the human OB with millisecond precision. We demonstrate that signals obtained via recordings from EEG electrodes at the nasal bridge represent responses from the human olfactory bulb - recordings we term Electrobulbogram (EBG). The EBG will aid future olfactory-related translational work but can also potentially be implemented as an everyday clinical tool to detect pathology-related changes in human central olfactory processing in neurodegenerative diseases. In conclusion, the EBG is localized to the OB, is reliable, and follows response patterns demonstrated in non-human animal models.
Topics: Adult; Electroencephalography; Female; Humans; Male; Olfactory Bulb; Young Adult
PubMed: 32005822
DOI: 10.1038/s41467-020-14520-9