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International Journal of Environmental... Oct 2018A major step in our understanding of brain function is to determine how neural circuits are altered in their function by signaling molecules or neuromodulators.... (Review)
Review
A major step in our understanding of brain function is to determine how neural circuits are altered in their function by signaling molecules or neuromodulators. Neuromodulation is the neurochemical process that modifies the computations performed by a neuron or network based on changing the functional needs or behavioral state of the subject. These modulations have the effect of altering the responsivity to synaptic inputs. Early sensory processing areas, such as the main olfactory bulb, provide an accessible window for investigating how neuromodulation regulates the functional states of neural networks and influences how we process sensory information. Olfaction is an attractive model system in this regard because of its relative simplicity and because it links primary olfactory sensory neurons to higher olfactory and associational networks. Likewise, centrifugal fibers from higher order brain centers target neurons in the main olfactory bulb to regulate synaptic processing. The neuromodulatory systems that provide regulatory inputs and play important roles in olfactory sensory processing and behaviors include the endocannabinoid system, the dopaminergic system, the cholinergic system, the noradrenergic system and the serotonergic system. Here, we present a brief survey of neuromodulation of olfactory signals in the main olfactory bulb with an emphasis on the endocannabinoid system.
Topics: Brain; Humans; Neurotransmitter Agents; Olfactory Bulb; Smell; Synaptic Transmission
PubMed: 30297631
DOI: 10.3390/ijerph15102194 -
Frontiers in Neural Circuits 2021Our sensory systems such as the olfactory and visual systems are the target of neuromodulatory regulation. This neuromodulation starts at the level of sensory receptors... (Review)
Review
Our sensory systems such as the olfactory and visual systems are the target of neuromodulatory regulation. This neuromodulation starts at the level of sensory receptors and extends into cortical processing. A relatively new group of neuromodulators includes cannabinoids. These form a group of chemical substances that are found in the cannabis plant. Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the main cannabinoids. THC acts in the brain and nervous system like the chemical substances that our body produces, the endogenous cannabinoids or endocannabinoids, also nicknamed the brain's own cannabis. While the function of the endocannabinoid system is understood fairly well in limbic structures such as the hippocampus and the amygdala, this signaling system is less well understood in the olfactory pathway and the visual system. Here, we describe and compare endocannabinoids as signaling molecules in the early processing centers of the olfactory and visual system, the olfactory bulb, and the retina, and the relevance of the endocannabinoid system for synaptic plasticity.
Topics: Animals; Cannabinoids; Humans; Neuronal Plasticity; Olfactory Bulb; Receptor, Cannabinoid, CB1; Retina; Smell; Visual Pathways; Visual Perception
PubMed: 34305536
DOI: 10.3389/fncir.2021.662349 -
Problemy Endokrinologii May 2023The majority of Kallmann patients have anosmia or hyposmia. This is how the disease is diagnosed. Some of them don't have such complaints but olfactory dysfunction is...
BACKGROUND
The majority of Kallmann patients have anosmia or hyposmia. This is how the disease is diagnosed. Some of them don't have such complaints but olfactory dysfunction is diagnosed via olfactometry. Nowadays there is the lack of information about correlation between olfactometry results and subjective complaints. Correlation between olfactory bulbs size and olfactory dysfunction has been little studied.
AIM
To explore olfactory bulb size and olfactory function in patients with congenital isolated hypogonadotropic hypogonadism. To correlate olfactory bulb sizes and smell test scores.
MATERIALS AND METHODS
Single-centre comparative study. 34 patients were included. The main group consisted of 19 patients with hypogonadotropic (15 -with Kallmann syndrome, 4 - with normosmic hypogonadism). Olfactory bulbs MRI were provided to all the patients, olfactory test (Sniffin' Sticks Test) and molecular-genetic studies were provided in all patients with hypogonadism. Control group consisted of 15 patients who were provided with orbits MRI. Olfactory bulbs were evaluated additionally in them.
RESULTS
Normal size of olfactory bulbs were only in 1 patient with hypogonadism. Olfactory bulbs height and width were significantly smaller in patients with hypogonadism in comparison with control group (p<0.01). Height median of right bulb was 1.0 mm [0.2; 1.8] in patients from the main group vs. 3.0 [2.5; 3.2] in controls, width median of right bulb was 1.0 mm [0.2; 1.9] in patients from the main group vs. 2.5 [2.0; 3.0] in controls. Height median of left bulb was 0.8 mm [0.0; 1.2] in patients from the main group vs. 3.0 [2.7; 3.2] in controls, width median of left bulb was 0.8 mm [0.0; 1.2] in patients from the main group vs. 2.5 [2.0; 3.0] in controls. Correlation has been established between left bulb height (r=0.59) and width (r=0.67) and olfactometry results (p<0.05). 4 patients had no anosmia complaints but had olfactory dysfunction according to Sniffin' Sticks Tests.
CONCLUSION
Olfactometry was able to diagnose olfactory dysfunction in 78.5% (i.e. in 15 out of 19 patients with congenital isolated hypogonadotropic hypogonadism. However, anosmia complaints had only 11 out of 19 patients. It is the first results of olfactory bulb sizes in patients with hypogonadotropic hypogonadism in Russia. Uni - or bilateral hypoor aplasia were diagnosed in 94.7% patients with hypogonadism regardless of olfactory dysfunction. Bilateral olfactory bulbs hypoplasia were the most common MRI-finding (36.8%). Unilateral hypoor aplasia was diagnosed in 31.6% patients.
Topics: Humans; Kallmann Syndrome; Olfactory Bulb; Olfaction Disorders; Hypogonadism; Smell; Anosmia
PubMed: 37448273
DOI: 10.14341/probl13216 -
Frontiers in Neural Circuits 2014Olfactory sensory neurons extend their axons solely to the olfactory bulb, which is dedicated to odor information processing. The olfactory bulb is divided into multiple... (Review)
Review
Olfactory sensory neurons extend their axons solely to the olfactory bulb, which is dedicated to odor information processing. The olfactory bulb is divided into multiple layers, with different types of neurons found in each of the layers. Therefore, neurons in the olfactory bulb have conventionally been categorized based on the layers in which their cell bodies are found; namely, juxtaglomerular cells in the glomerular layer, tufted cells in the external plexiform layer, mitral cells in the mitral cell layer, and granule cells in the granule cell layer. More recently, numerous studies have revealed the heterogeneous nature of each of these cell types, allowing them to be further divided into subclasses based on differences in morphological, molecular, and electrophysiological properties. In addition, technical developments and advances have resulted in an increasing number of studies regarding cell types other than the conventionally categorized ones described above, including short-axon cells and adult-generated interneurons. Thus, the expanding diversity of cells in the olfactory bulb is now being acknowledged. However, our current understanding of olfactory bulb neuronal circuits is mostly based on the conventional and simplest classification of cell types. Few studies have taken neuronal diversity into account for understanding the function of the neuronal circuits in this region of the brain. This oversight may contribute to the roadblocks in developing more precise and accurate models of olfactory neuronal networks. The purpose of this review is therefore to discuss the expanse of existing work on neuronal diversity in the olfactory bulb up to this point, so as to provide an overall picture of the olfactory bulb circuit.
Topics: Animals; Models, Neurological; Nerve Net; Neurons; Olfactory Bulb; Synapses; Synaptic Transmission
PubMed: 25232305
DOI: 10.3389/fncir.2014.00098 -
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 -
Seminars in Cell & Developmental Biology Sep 2022Olfactory dysfunction is often the earliest indicator of disease in a range of neurological and psychiatric disorders. One tempting working hypothesis is that... (Review)
Review
Olfactory dysfunction is often the earliest indicator of disease in a range of neurological and psychiatric disorders. One tempting working hypothesis is that pathological changes in the peripheral olfactory system where the body is exposed to many adverse environmental stressors may have a causal role for the brain alteration. Whether and how the peripheral pathology spreads to more central brain regions may be effectively studied in rodent models, and there is successful precedence in experimental models for Parkinson's disease. It is of interest to study whether a similar mechanism may underlie the pathology of psychiatric illnesses, such as schizophrenia. However, direct comparison between rodent models and humans includes challenges under light of comparative neuroanatomy and experimental methodologies used in these two distinct species. We believe that neuroimaging modality that has been the main methodology of human brain studies may be a useful viewpoint to address and fill the knowledge gap between rodents and humans in this scientific question. Accordingly, in the present review article, we focus on brain imaging studies associated with olfaction in healthy humans and patients with neurological and psychiatric disorders, and if available those in rodents. We organize this review article at three levels: 1) olfactory bulb (OB) and peripheral structures of the olfactory system, 2) primary olfactory cortical and subcortical regions, and 3) associated higher-order cortical regions. This research area is still underdeveloped, and we acknowledge that further validation with independent cohorts may be needed for many studies presented here, in particular those with human subjects. Nevertheless, whether and how peripheral olfactory disturbance impacts brain function is becoming even a hotter topic in the ongoing COVID-19 pandemic, given the risk of long-term changes of mental status associated with olfactory infection of SARS-CoV-2. Together, in this review article, we introduce this underdeveloped but important research area focusing on its implications in neurological and psychiatric disorders, with several pioneered publications.
Topics: COVID-19; Humans; Neuroimaging; Olfaction Disorders; Olfactory Bulb; Pandemics; SARS-CoV-2; Smell
PubMed: 34462249
DOI: 10.1016/j.semcdb.2021.08.009 -
International Journal of Molecular... Apr 2019The olfactory system, composed of the olfactory organs and the olfactory bulb, allows organisms to interact with their environment and through the detection of odor... (Review)
Review
The olfactory system, composed of the olfactory organs and the olfactory bulb, allows organisms to interact with their environment and through the detection of odor signals. Olfaction mediates behaviors pivotal for survival, such as feeding, mating, social behavior, and danger assessment. The olfactory organs are directly exposed to the milieu, and thus are particularly vulnerable to damage by environmental pollutants and toxicants, such as heavy metals, pesticides, and surfactants, among others. Given the widespread occurrence of olfactory toxicants, there is a pressing need to understand the effects of these harmful compounds on olfactory function. Zebrafish () is a valuable model for studying human physiology, disease, and toxicity. Additionally, the anatomical components of the zebrafish olfactory system are similar to those of other vertebrates, and they present a remarkable degree of regeneration and neuroplasticity, making it an ideal model for the study of regeneration, reorganization and repair mechanisms following olfactory toxicant exposure. In this review, we focus on (1) the anatomical, morphological, and functional organization of the olfactory system of zebrafish; (2) the adverse effects of olfactory toxicants and injury to the olfactory organ; and (3) remodeling and repair neuroplasticity mechanisms following injury and degeneration by olfactory toxicant exposure.
Topics: Animals; Disease Models, Animal; Neuronal Plasticity; Neurotoxicity Syndromes; Odorants; Olfactory Bulb; Zebrafish
PubMed: 30986990
DOI: 10.3390/ijms20071639 -
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 -
Seminars in Cell & Developmental Biology Nov 2014Recent studies using molecular genetics, electrophysiology, in vivo imaging, and behavioral analyses have elucidated detailed connectivity and function of the mammalian... (Review)
Review
Recent studies using molecular genetics, electrophysiology, in vivo imaging, and behavioral analyses have elucidated detailed connectivity and function of the mammalian olfactory circuits. The olfactory bulb is the first relay station of olfactory perception in the brain, but it is more than a simple relay: olfactory information is dynamically tuned by local olfactory bulb circuits and converted to spatiotemporal neural code for higher-order information processing. Because the olfactory bulb processes ∼1000 discrete input channels from different odorant receptors, it serves as a good model to study neuronal wiring specificity, from both functional and developmental aspects. This review summarizes our current understanding of the olfactory bulb circuitry from functional standpoint and discusses important future studies with particular focus on its development and plasticity.
Topics: Animals; Humans; Models, Neurological; Nerve Net; Neuronal Plasticity; Neurons; Odorants; Olfactory Bulb; Olfactory Pathways; Smell
PubMed: 25084319
DOI: 10.1016/j.semcdb.2014.07.012 -
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