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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 -
Cell Oct 2022In most sensory modalities, neuronal connectivity reflects behaviorally relevant stimulus features, such as spatial location, orientation, and sound frequency. By...
In most sensory modalities, neuronal connectivity reflects behaviorally relevant stimulus features, such as spatial location, orientation, and sound frequency. By contrast, the prevailing view in the olfactory cortex, based on the reconstruction of dozens of neurons, is that connectivity is random. Here, we used high-throughput sequencing-based neuroanatomical techniques to analyze the projections of 5,309 mouse olfactory bulb and 30,433 piriform cortex output neurons at single-cell resolution. Surprisingly, statistical analysis of this much larger dataset revealed that the olfactory cortex connectivity is spatially structured. Single olfactory bulb neurons targeting a particular location along the anterior-posterior axis of piriform cortex also project to matched, functionally distinct, extra-piriform targets. Moreover, single neurons from the targeted piriform locus also project to the same matched extra-piriform targets, forming triadic circuit motifs. Thus, as in other sensory modalities, olfactory information is routed at early stages of processing to functionally diverse targets in a coordinated manner.
Topics: Mice; Animals; Olfactory Pathways; Olfactory Cortex; Olfactory Bulb; Neurons; High-Throughput Nucleotide Sequencing
PubMed: 36306734
DOI: 10.1016/j.cell.2022.09.038 -
Annual Review of Physiology Feb 2021In mammals, odor information detected by olfactory sensory neurons is converted to a topographic map of activated glomeruli in the olfactory bulb. Mitral cells and... (Review)
Review
In mammals, odor information detected by olfactory sensory neurons is converted to a topographic map of activated glomeruli in the olfactory bulb. Mitral cells and tufted cells transmit signals sequentially to the olfactory cortex for behavioral outputs. To elicit innate behavioral responses, odor signals are directly transmitted by distinct subsets of mitral cells from particular functional domains in the olfactory bulb to specific amygdala nuclei. As for the learned decisions, input signals are conveyed by tufted cells as well as by mitral cells to the olfactory cortex. Behavioral scene cells link the odor information to the valence cells in the amygdala to elicit memory-based behavioral responses. Olfactory decision and perception take place in relation to the respiratory cycle. How is the sensory quality imposed on the olfactory inputs for behavioral outputs? How are the two types of odor signals, innate and learned, processed during respiration? Here, we review recent progress on the study of neural circuits involved in decision making in the mouse olfactory system.
Topics: Amygdala; Animals; Humans; Neurons; Olfactory Bulb; Olfactory Cortex; Smell
PubMed: 33228453
DOI: 10.1146/annurev-physiol-031820-092824 -
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 -
PLoS Pathogens Jan 2021Neuropilin-1 (NRP-1), a member of a family of signaling proteins, was shown to serve as an entry factor and potentiate SARS Coronavirus 2 (SARS-CoV-2) infectivity in... (Review)
Review
Neuropilin-1 (NRP-1), a member of a family of signaling proteins, was shown to serve as an entry factor and potentiate SARS Coronavirus 2 (SARS-CoV-2) infectivity in vitro. This cell surface receptor with its disseminated expression is important in angiogenesis, tumor progression, viral entry, axonal guidance, and immune function. NRP-1 is implicated in several aspects of a SARS-CoV-2 infection including possible spread through the olfactory bulb and into the central nervous system and increased NRP-1 RNA expression in lungs of severe Coronavirus Disease 2019 (COVID-19). Up-regulation of NRP-1 protein in diabetic kidney cells hint at its importance in a population at risk of severe COVID-19. Involvement of NRP-1 in immune function is compelling, given the role of an exaggerated immune response in disease severity and deaths due to COVID-19. NRP-1 has been suggested to be an immune checkpoint of T cell memory. It is unknown whether involvement and up-regulation of NRP-1 in COVID-19 may translate into disease outcome and long-term consequences, including possible immune dysfunction. It is prudent to further research NRP-1 and its possibility of serving as a therapeutic target in SARS-CoV-2 infections. We anticipate that widespread expression, abundance in the respiratory and olfactory epithelium, and the functionalities of NRP-1 factor into the multiple systemic effects of COVID-19 and challenges we face in management of disease and potential long-term sequelae.
Topics: COVID-19; Diabetic Nephropathies; Humans; Immunologic Memory; Neuropilin-1; Olfactory Bulb; Respiratory Mucosa; SARS-CoV-2; T-Lymphocytes; Virus Internalization
PubMed: 33395426
DOI: 10.1371/journal.ppat.1009153 -
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 -
Current Opinion in Neurobiology Oct 2020Olfaction is crucial for animal survival and human well-being. The olfactory bulb is the obligatory input station for olfactory information. In contrast to the... (Review)
Review
Olfaction is crucial for animal survival and human well-being. The olfactory bulb is the obligatory input station for olfactory information. In contrast to the traditional view as a static relay station, recent evidence indicates that the olfactory bulb dynamically processes olfactory information in an experience-dependent and context-dependent manner. Here, we review recent studies on experience-dependent plasticity of the main circuit components within the olfactory bulb of rodents. We argue that the olfactory bulb plasticity allows optimal representations of behaviorally-relevant odors in the continuously changing olfactory environment.
Topics: Animals; Odorants; Olfactory Bulb; Olfactory Pathways; Smell
PubMed: 32062045
DOI: 10.1016/j.conb.2020.01.007 -
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 -
Seminars in Ultrasound, CT, and MR Oct 2022The human sense of smell is the unique sense through which the olfactory system can identify aromatic molecules within the air and provide a taste sensation. Still, also...
The human sense of smell is the unique sense through which the olfactory system can identify aromatic molecules within the air and provide a taste sensation. Still, also it plays an essential role in several other functions, warning about environmental safety and even impacts our emotional lives. Recently, olfactory impairment has become an issue of interest due to the COVID-19 pandemic. The dysfunction may vary from only reduced smell detection (hyposmia) to complete loss of it (anosmia) but also includes changes in the normal perception of odors (parosmia). Computed tomography and magnetic imaging resonance are the modalities of choice to evaluate the olfactory pathways. Computed tomography is the initial imaging modality for olfactory disturbances, allowing recognition of sinonasal pathologies, inflammatory processes, or bone-related tumors. Magnetic imaging resonance with dedicated protocols for olfactory disorders enables a detailed assessment of the sinonasal compartment and the anterior cranial fossa. Provides a better depiction of olfactory bulb volume, morphology and signal intensity, as well the status of signal intensity of the central olfactory projection areas. Several diseases can affect the olfactory nerve, such as congenital disorders, trauma, inflammatory or infectious diseases, neoplasms, and even post-operative involvement. This article aims to review the normal anatomy of the olfactory nerve pathway and highlight the spectrum of conditions that most commonly affect it.
Topics: COVID-19; Humans; Olfaction Disorders; Olfactory Bulb; Olfactory Nerve; Pandemics
PubMed: 36116849
DOI: 10.1053/j.sult.2022.04.001