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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 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 -
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 -
The Journal of Comparative Neurology Aug 2022Olfactory epithelium (OE) is capable of lifelong regeneration due to presence of basal progenitor cells that respond to injury or neuronal loss with increased activity....
Olfactory epithelium (OE) is capable of lifelong regeneration due to presence of basal progenitor cells that respond to injury or neuronal loss with increased activity. However, this capability diminishes with advancing age and a decrease in odor perception in older individuals is well established. To characterize changes associated with age in the peripheral olfactory system, an in-depth analysis of the OE and its neuronal projections onto the olfactory bulb (OB) as a function of age was performed. Human olfactory tissue autopsy samples from 36 subjects with an average age of 74.1 years were analyzed. Established cell type-specific antibodies were used to identify OE component cells in whole mucosal sheets and epithelial sections as well as glomeruli and periglomerular structures in OB sections. With age, a reduction in OE area occurs across the mucosa progressing in a posterior-dorsal direction. Deterioration of the olfactory system is accompanied with diminution of neuron-containing OE, mature olfactory sensory neurons (OSNs) and OB innervation. On an individual level, the neuronal density within the epithelium appears to predict synapse density within the OB. The innervation of the OB is uneven with higher density at the ventral half that decreases with age as opposed to stable innervation at the dorsal half. Respiratory metaplasia, submucosal cysts, and neuromata, were commonly identified in aged OE. The finding of respiratory metaplasia and aneuronal epithelium with reduction in global basal cells suggests a progression of stem cell quiescence as an underlying pathophysiology of age-related smell loss in humans. KEY POINTS: A gradual loss of olfactory sensory neurons with age in human olfactory epithelium is also reflected in a reduction in glomeruli within the olfactory bulb. This gradual loss of neurons and synaptic connections with age occurs in a specific, spatially inhomogeneous manner. Decreasing mitotically active olfactory epithelium basal cells may contribute to age-related neuronal decline and smell loss in humans.
Topics: Aged; Anosmia; Humans; Metaplasia; Olfactory Bulb; Olfactory Mucosa; Olfactory Receptor Neurons
PubMed: 35397118
DOI: 10.1002/cne.25325 -
Cell and Tissue Research Jan 2021The ability of the olfactory system to detect and discriminate a broad spectrum of odor molecules with extraordinary sensitivity relies on a wide range of odorant... (Review)
Review
The ability of the olfactory system to detect and discriminate a broad spectrum of odor molecules with extraordinary sensitivity relies on a wide range of odorant receptors and on the distinct architecture of neuronal circuits in olfactory brain areas. More than 1000 odorant receptors, distributed almost randomly in the olfactory epithelium, are plotted out in two mirror-symmetric maps of glomeruli in the olfactory bulb, the first relay station of the olfactory system. How does such a precise spatial arrangement of glomeruli emerge from a random distribution of receptor neurons? Remarkably, the identity of odorant receptors defines not only the molecular receptive range of sensory neurons but also their glomerular target. Despite their key role, odorant receptors are not the only determinant, since the specificity of neuronal connections emerges from a complex interplay between several molecular cues and electrical activity. This review provides an overview of the mechanisms underlying olfactory circuit formation. In particular, recent findings on the role of odorant receptors in regulating axon targeting and of spontaneous activity in the development and maintenance of synaptic connections are discussed.
Topics: Animals; Brain Mapping; Odorants; Olfactory Bulb
PubMed: 33404841
DOI: 10.1007/s00441-020-03348-w -
Chemical Senses Jun 2017Interactions with the environment depend not only on sensory perception of external stimuli but also on processes of neuromodulation regulated by the internal state of... (Review)
Review
Interactions with the environment depend not only on sensory perception of external stimuli but also on processes of neuromodulation regulated by the internal state of an organism. These processes allow regulation of stimulus detection to match the demands of an organism influenced by its general brain state (satiety, wakefulness/sleep state, attentiveness, arousal, learning etc.). The sense of smell is initiated by sensory neurons located in the nasal cavity that recognize environmental odorants and project axons into the olfactory bulb (OB), where they form synapses with several types of neurons. Modulations of early synaptic circuits are particularly important since these can affect all subsequent processing steps. While the precise mechanisms have not been fully elucidated, work from many labs has demonstrated that the activity of neurons in the OB and cortex can be modulated by different factors inducing specific changes to olfactory information processing. The symposium "Neuromodulation in Chemosensory Pathways" at the International Symposium on Olfaction and Taste (ISOT 2016) highlighted some of the most recent advances in state-dependent network modulations of the mouse olfactory system including modulation mediated by specific neurotransmitters and neuroendocrine molecules, involving pharmacological, electrophysiological, learning, and behavioral approaches.
Topics: Animals; Neurotransmitter Agents; Olfactory Bulb; Sensory Receptor Cells; Smell
PubMed: 28379355
DOI: 10.1093/chemse/bjx014 -
Cell and Tissue Research Jan 2021Evolutionarily, olfaction is one of the oldest senses and pivotal for an individual's health and survival. The olfactory bulb (OB), as the first olfactory relay station... (Review)
Review
Evolutionarily, olfaction is one of the oldest senses and pivotal for an individual's health and survival. The olfactory bulb (OB), as the first olfactory relay station in the brain, is known to heavily process sensory information. To adapt to an animal's needs, OB activity can be influenced by many factors either from within (intrinsic neuromodulation) or outside (extrinsic neuromodulation) the OB which include neurotransmitters, neuromodulators, hormones, and neuropeptides. Extrinsic sources seem to be of special importance as the OB receives massive efferent input from numerous brain centers even outweighing the sensory input from the nose. Here, we review neuromodulatory processes in the rodent OB from such extrinsic sources. We will discuss extrinsic neuromodulation according to points of origin, receptors involved, affected circuits, and changes in behavior. In the end, we give a brief outlook on potential future directions in research on neuromodulation in the OB.
Topics: Animals; Olfactory Bulb; Rodentia
PubMed: 33355709
DOI: 10.1007/s00441-020-03365-9 -
Cold Spring Harbor Perspectives in... Aug 2016Most organisms use their olfactory system to detect and analyze chemical cues from the external world to guide essential behaviors. From worms to vertebrates, chemicals... (Review)
Review
Most organisms use their olfactory system to detect and analyze chemical cues from the external world to guide essential behaviors. From worms to vertebrates, chemicals are detected by odorant receptors expressed by olfactory sensory neurons, which in vertebrates send an axon to the primary processing center called the olfactory bulb (OB). Within the OB, sensory neurons form excitatory synapses with projection neurons and with inhibitory interneurons. Thus, because of complex synaptic interactions, the output of a given projection neuron is determined not only by the sensory input, but also by the activity of local inhibitory interneurons that are regenerated throughout life in the process of adult neurogenesis. Herein, we discuss how it is optimized and why.
Topics: Age Factors; Animals; Interneurons; Neurogenesis; Olfactory Bulb
PubMed: 27235474
DOI: 10.1101/cshperspect.a018945 -
Genes Apr 2020Olfaction has a direct influence on behavior and cognitive processes. There are different neuromodulatory systems in olfactory circuits that control the sensory... (Review)
Review
Olfaction has a direct influence on behavior and cognitive processes. There are different neuromodulatory systems in olfactory circuits that control the sensory information flowing through the rest of the brain. The presence of the cannabinoid type-1 (CB1) receptor, (the main cannabinoid receptor in the brain), has been shown for more than 20 years in different brain olfactory areas. However, only over the last decade have we started to know the specific cellular mechanisms that link cannabinoid signaling to olfactory processing and the control of behavior. In this review, we aim to summarize and discuss our current knowledge about the presence of CB1 receptors, and the function of the endocannabinoid system in the regulation of different olfactory brain circuits and related behaviors.
Topics: Animals; Brain; Cannabinoids; Humans; Olfactory Bulb; Receptors, Cannabinoid; Smell
PubMed: 32316252
DOI: 10.3390/genes11040431 -
Arquivos de Neuro-psiquiatria Apr 2016Pathology of the rhinencephalon has been a subject of interest in the fields of neurodegenerative diseases, trauma, epilepsy and other neurological conditions. Most of... (Review)
Review
Pathology of the rhinencephalon has been a subject of interest in the fields of neurodegenerative diseases, trauma, epilepsy and other neurological conditions. Most of what is known about the human rhinencephalon comes from comparative anatomy studies in other mammals and histological studies in primates. Functional imaging studies can provide new and important insight into the function of the rhinencephalon in humans but have limited spatial resolution, limiting its contribution to the study of the anatomy of the human rhinencephalon. In this study we aim to provide a brief and objective review of the anatomy of this important and often overlooked area of the nervous system.
Topics: Humans; Medical Illustration; Olfactory Bulb; Olfactory Cortex; Olfactory Mucosa; Olfactory Receptor Neurons
PubMed: 27097007
DOI: 10.1590/0004-282X20160043