-
Neuron Jul 2023Although the etiology of major depressive disorder remains poorly understood, reduced gamma oscillations is an emerging biomarker. Olfactory bulbectomy, an established...
Although the etiology of major depressive disorder remains poorly understood, reduced gamma oscillations is an emerging biomarker. Olfactory bulbectomy, an established model of depression that reduces limbic gamma oscillations, suffers from non-specific effects of structural damage. Here, we show that transient functional suppression of olfactory bulb neurons or their piriform cortex efferents decreased gamma oscillation power in limbic areas and induced depression-like behaviors in rodents. Enhancing transmission of gamma oscillations from olfactory bulb to limbic structures by closed-loop electrical neuromodulation alleviated these behaviors. By contrast, silencing gamma transmission by anti-phase closed-loop stimulation strengthened depression-like behaviors in naive animals. These induced behaviors were neutralized by ketamine treatment that restored limbic gamma power. Taken together, our results reveal a causal link between limbic gamma oscillations and depression-like behaviors in rodents. Interfering with these endogenous rhythms can affect behaviors in rodent models of depression, suggesting that restoring gamma oscillations may alleviate depressive symptoms.
Topics: Animals; Olfactory Bulb; Rodentia; Depression; Depressive Disorder, Major; Neurons
PubMed: 37164008
DOI: 10.1016/j.neuron.2023.04.013 -
Handbook of Clinical Neurology 2019Axons from the olfactory bulb (OB) project to multiple central structures of the brain, many of which, in turn, send axons back into the OB and/or to one another. These... (Review)
Review
Axons from the olfactory bulb (OB) project to multiple central structures of the brain, many of which, in turn, send axons back into the OB and/or to one another. These secondary sensory regions underlie many aspects of odor representation, valence, and learning, as well as serving some nonolfactory functions, though many details remain unclear. We here describe the connectivity and essential structural and functional properties of these postbulbar olfactory regions in the mammalian brain.
Topics: Animals; Axons; Behavior; Brain; Humans; Learning; Olfactory Bulb; Smell
PubMed: 31604565
DOI: 10.1016/B978-0-444-63855-7.00006-X -
Cell and Tissue Research Jan 2021
Topics: Animals; Humans; Odorants; Olfactory Bulb; Olfactory Cortex; Olfactory Mucosa; Olfactory Pathways; Olfactory Perception; Receptors, Odorant; Smell
PubMed: 33447882
DOI: 10.1007/s00441-020-03389-1 -
Acta Neuropathologica Communications May 2024The majority of patients with Parkinson disease (PD) experience a loss in their sense of smell and accumulate insoluble α-synuclein aggregates in their olfactory bulbs...
The majority of patients with Parkinson disease (PD) experience a loss in their sense of smell and accumulate insoluble α-synuclein aggregates in their olfactory bulbs (OB). Subjects affected by a SARS-CoV-2-linked illness (COVID-19) also frequently experience hyposmia. We previously postulated that microglial activation as well as α-synuclein and tau misprocessing can occur during host responses following microbial encounters. Using semiquantitative measurements of immunohistochemical signals, we examined OB and olfactory tract specimens collected serially at autopsies between 2020 and 2023. Deceased subjects comprised 50 adults, which included COVID19 + patients (n = 22), individuals with Lewy body disease (e.g., PD; dementia with Lewy bodies (n = 6)), Alzheimer disease (AD; n = 3), and other neurodegenerative disorders (e.g., progressive supranuclear palsy (n = 2); multisystem atrophy (n = 1)). Further, we included neurologically healthy controls (n = 9), and added subjects with an inflammation-rich brain disorder as neurological controls (NCO; n = 7). When probing for microglial and histiocytic reactivity in the anterior olfactory nuclei (AON) by anti-CD68 immunostaining, scores were consistently elevated in NCO and AD cases. In contrast, microglial signals on average were not significantly altered in COVID19 + patients relative to healthy controls, although anti-CD68 reactivity in their OB and tracts declined with progression in age. Mild-to-moderate increases in phospho-α-synuclein and phospho-tau signals were detected in the AON of tauopathy- and synucleinopathy-afflicted brains, respectively, consistent with mixed pathology, as described by others. Lastly, when both sides were available for comparison in our case series, we saw no asymmetry in the degree of pathology of the left versus right OB and tracts. We concluded from our autopsy series that after a fatal course of COVID-19, microscopic changes in the rostral, intracranial portion of the olfactory circuitry -when present- reflected neurodegenerative processes seen elsewhere in the brain. In general, microglial reactivity correlated best with the degree of Alzheimer's-linked tauopathy and declined with progression of age in COVID19 + patients.
Topics: Humans; COVID-19; Olfactory Bulb; Aged; Male; Female; Aged, 80 and over; Middle Aged; Microglia; alpha-Synuclein; tau Proteins; SARS-CoV-2; Neurodegenerative Diseases
PubMed: 38698465
DOI: 10.1186/s40478-024-01761-8 -
Current Opinion in Neurobiology Oct 2016The olfactory bulb and piriform cortex are the best studied structures of the mammalian olfactory system and are heavily innervated by extrinsic neuromodulatory inputs.... (Review)
Review
The olfactory bulb and piriform cortex are the best studied structures of the mammalian olfactory system and are heavily innervated by extrinsic neuromodulatory inputs. The state-dependent release of acetylcholine, norepinephrine, serotonin, and other neuromodulators into these olfactory structures alters a constellation of physiological parameters in neurons and synapses that together modify the computations performed on sensory signals. These modifications affect the specificity, detectability, discriminability, and other properties of odor representations and thereby govern perceptual performance. Whereas different neuromodulators have distinct cellular effects, and tend to be associated with nominally different functions, it also is clear that these purported functions overlap substantially, and that ad hoc hypotheses regarding the roles of particular neuromodulators may have reached the limits of their usefulness.
Topics: Acetylcholine; Animals; Neurons; Olfactory Bulb; Smell
PubMed: 27564660
DOI: 10.1016/j.conb.2016.07.006 -
Science (New York, N.Y.) Nov 2023Adult neural stem cells (NSCs) contribute to lifelong brain plasticity. In the adult mouse ventricular-subventricular zone, NSCs are heterogeneous and, depending on...
Adult neural stem cells (NSCs) contribute to lifelong brain plasticity. In the adult mouse ventricular-subventricular zone, NSCs are heterogeneous and, depending on their location in the niche, give rise to different subtypes of olfactory bulb (OB) interneurons. Here, we show that multiple regionally distinct NSCs, including domains that are usually quiescent, are recruited on different gestation days during pregnancy. Synchronized activation of these adult NSC pools generates transient waves of short-lived OB interneurons, especially in layers with less neurogenesis under homeostasis. Using spatial transcriptomics, we identified molecular markers of pregnancy-associated interneurons and showed that some subsets are temporarily needed for own pup recognition. Thus, pregnancy triggers transient yet behaviorally relevant neurogenesis, highlighting the physiological relevance of adult stem cell heterogeneity.
Topics: Animals; Female; Mice; Pregnancy; Adult Stem Cells; Interneurons; Lateral Ventricles; Neural Stem Cells; Neurogenesis; Neuronal Plasticity; Olfactory Bulb; Smell; Transcriptome; Maternal Behavior
PubMed: 37995223
DOI: 10.1126/science.abo5199 -
Development (Cambridge, England) Feb 2022The mammalian main olfactory bulb is a crucial processing centre for the sense of smell. The olfactory bulb forms early during development and is functional from birth.... (Review)
Review
The mammalian main olfactory bulb is a crucial processing centre for the sense of smell. The olfactory bulb forms early during development and is functional from birth. However, the olfactory system continues to mature and change throughout life as a target of constitutive adult neurogenesis. Our Review synthesises current knowledge of prenatal, postnatal and adult olfactory bulb development, focusing on the maturation, morphology, functions and interactions of its diverse constituent glutamatergic and GABAergic cell types. We highlight not only the great advances in the understanding of olfactory bulb development made in recent years, but also the gaps in our present knowledge that most urgently require addressing.
Topics: Animals; Axons; Bone Morphogenetic Proteins; Neurogenesis; Olfactory Bulb; Olfactory Receptor Neurons; Signal Transduction; Synapses
PubMed: 35147186
DOI: 10.1242/dev.200210 -
Omics : a Journal of Integrative Biology Jan 2018Human olfactory tract plays a fundamental role in health and disease. Proteomic analysis of the olfactory tract therefore bears fundamental importance for integrative... (Review)
Review
Human olfactory tract plays a fundamental role in health and disease. Proteomic analysis of the olfactory tract therefore bears fundamental importance for integrative biology and clinical medicine. For example, olfactory dysfunction is one of the earliest findings in neurodegenerative disorders. The objective of the present study was to build the proteome data from human olfactory tract using a mass spectrometry-based approach. We performed a shotgun proteomic analysis of the human olfactory tract obtained from three healthy adult male subjects. The proteomics workflow consisted of fractionation based on high pH reverse phase liquid chromatography and SDS-PAGE, followed by liquid chromatography tandem-mass spectrometry (LC-MS/MS) analysis on high-resolution mass spectrometer. In total, 6055 proteins were identified, which were further subjected to bioinformatics analysis and contextualization to identify the associated biological processes and molecular functions. We found the identified proteins involved in processes and functions related to olfactory perception, cell to cell adhesion, cellular and G-coupled receptor activity, axonal growth, and transportation. Importantly, we report the identification of 83 olfactory tract-restricted proteins, 4 seven-transmembrane proteins, and 14 protein kinases. Pathway analysis of the restricted proteins revealed the enrichment of olfactory transduction, adherens junction, taste transduction, and neurotropic signaling pathways. To the best of our knowledge, this is the first study to report the human olfactory tract proteome. The study contributes to the knowledge of the human brain proteome and forms a crucial knowledge base for future applications in basic and clinical research, especially in olfactory sensation and neurodegenerative human disorders.
Topics: Animals; Chromatography, Liquid; Computational Biology; Gene Ontology; Humans; Hydrogen-Ion Concentration; Molecular Sequence Annotation; Olfactory Bulb; Organ Specificity; Protein Interaction Mapping; Protein Interaction Maps; Proteome; Proteomics; Signal Transduction; Tandem Mass Spectrometry
PubMed: 29356628
DOI: 10.1089/omi.2017.0155 -
Frontiers in Neuroendocrinology Oct 2018Different conditions induce proliferation, migration and integration of new neurons in the adult brain. This process of neurogenesis is a clear example of long lasting... (Review)
Review
Different conditions induce proliferation, migration and integration of new neurons in the adult brain. This process of neurogenesis is a clear example of long lasting plastic changes in the brain of different species. Sexual behavior is a motivated behavior that is crucial for the survival of the species, but an individual can spend all his life without displaying sexual behavior. In the present review, we briefly describe some of the effects of pheromones on neurogenesis. We review in detail studies describing the effects of sexual behavior in both males and females on proliferation, migration and integration of new cells and neurons. It will become evident that most of the studies have been done in rodents, assessing the effects of this behavior on neurogenesis within the dentate gyrus of the hippocampus and in the subventricular zone - rostral migratory stream - olfactory bulb system.
Topics: Animals; Female; Hippocampus; Male; Neurogenesis; Olfactory Bulb; Pheromones; Sexual Behavior, Animal
PubMed: 29438737
DOI: 10.1016/j.yfrne.2018.02.004 -
The Consultant Pharmacist : the Journal... Nov 2016Estimates indicate that 14 million Americans have olfactory dysfunction. As with other senses, such as sight and hearing, olfaction frequently declines with age.... (Review)
Review
Estimates indicate that 14 million Americans have olfactory dysfunction. As with other senses, such as sight and hearing, olfaction frequently declines with age. Impaired olfaction can be a warning sign of Parkinson's disease, sometimes occurring before motor symptoms develop. It's also an initial symptom of Alzheimer's dementia (AD); the amyloid plaques and tangles characterizing AD invade the olfactory bulb and hippocampus early in its course, hampering odor identification. Olfactory dysfunction is associated with some serious problems, including inability to smell warning odors (fire, gas) and impaired ability to taste food. Standardized, validated methods are available to measure several different dimensions of olfactory function, including odor identification, discrimination, and threshold levels. Researchers are currently studying the unique olfactory deficits associated with different conditions in hopes of identifying new, noninvasive tools for early diagnosis and treatment. Drugs may cause or contribute to olfactory dysfunction, but it can be difficult to pinpoint offending medications.
Topics: Age Factors; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Olfaction Disorders; Olfactory Bulb; Olfactory Perception; Olfactory Receptor Neurons; Quality of Life; Risk Factors; Sex Factors; Signal Transduction; Smell
PubMed: 28107119
DOI: 10.4140/TCP.n.2016.624