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The Journal of Neuroscience : the... Feb 2023The accessory olfactory system (AOS) is critical for the development and expression of social behavior. The first dedicated circuit in the AOS, the accessory olfactory...
The accessory olfactory system (AOS) is critical for the development and expression of social behavior. The first dedicated circuit in the AOS, the accessory olfactory bulb (AOB), exhibits cellular and network plasticity in male and female mice after social experience. In the AOB, interneurons called internal granule cells (IGCs) express the plasticity-associated immediate-early gene following intermale aggression or mating. Here, we sought to better understand how -expressing IGCs shape AOB information processing and social behavior in the context of territorial aggression. We used "ArcTRAP" (Arc-CreERT2) transgenic mice to selectively and permanently label -expressing IGCs following male-male resident-intruder interactions. Using whole-cell patch-clamp electrophysiology, we found that -expressing IGCs display increased intrinsic excitability for several days after a single resident-intruder interaction. Further, we found that -expressing IGCs maintain this increased excitability across repeated resident-intruder interactions, during which resident mice increase or "ramp" their aggression. We tested the hypothesis that -expressing IGCs participate in ramping aggression. Using a combination of ArcTRAP mice and chemogenetics (Cre-dependent hM4D(G)-mCherry AAV injections), we found that disruption of -expressing IGC activity during repeated resident-intruder interactions abolishes the ramping aggression exhibited by resident male mice. This work shows that -expressing AOB IGC ensembles are activated by specific chemosensory environments, and play an integral role in the establishment and expression of sex-typical social behavior. These studies identify a population of plastic interneurons in an early chemosensory circuit that display physiological features consistent with simple memory formation, increasing our understanding of central chemosensory processing and mammalian social behavior. The accessory olfactory system plays a vital role in rodent chemosensory social behavior. We studied experience-dependent plasticity in the accessory olfactory bulb and found that internal granule cells expressing the immediate-early gene after the resident-intruder paradigm increase their excitability for several days. We investigated the roles of these -expressing internal granule cells on chemosensory social behavior by chemogenetically manipulating their excitability during repeated social interactions. We found that inhibiting these cells eliminated intermale aggressive ramping behavior. These studies identify a population of plastic interneurons in an early chemosensory circuit that display physiological features consistent with simple memory formation, increasing our understanding of central chemosensory processing and mammalian social behavior.
Topics: Mice; Male; Female; Animals; Olfactory Bulb; Interneurons; Neurons; Social Behavior; Aggression; Mice, Transgenic; Mammals
PubMed: 36623874
DOI: 10.1523/JNEUROSCI.0847-22.2022 -
Development, Growth & Differentiation May 2020In mammals, odorants induce various behavioral responses that are critical to the survival of the individual and species. Binding signals of odorants to odorant... (Review)
Review
In mammals, odorants induce various behavioral responses that are critical to the survival of the individual and species. Binding signals of odorants to odorant receptors (ORs) expressed in the olfactory epithelia are converted to an odor map, a pattern of activated glomeruli, in the olfactory bulb (OB). This topographic map is used to identify odorants for memory-based learned decisions. In the embryo, a coarse olfactory map is generated in the OB by a combination of dorsal-ventral and anterior-posterior targeting of olfactory sensory neurons (OSNs), using specific sets of axon-guidance molecules. During the process of OSN projection, odor signals are sorted into distinct odor qualities in separate functional domains in the OB. Odor information is then conveyed by the projection neurons, mitral/tufted cells, to various regions in the olfactory cortex, particularly to the amygdala for innate olfactory decisions. Although the basic architecture of hard-wired circuits is generated by a genetic program, innate olfactory responses are modified by neonatal odor experience in an activity-dependent manner. Stimulus-driven OR activity promotes post-synaptic events and dendrite selection in the responding glomeruli making them larger. As a result, enhanced odor inputs in neonates establish imprinted olfactory memory that induces attractive responses in adults, even when the odor quality is innately aversive. In this paper, I will provide an overview of the recent progress made in the olfactory circuit formation in mice.
Topics: Animals; Mice; Odorants; Olfactory Bulb; Olfactory Receptor Neurons; Receptors, Odorant
PubMed: 32112394
DOI: 10.1111/dgd.12657 -
Brain Pathology (Zurich, Switzerland) May 2022Several degenerative brain disorders such as Alzheimer's disease (AD), Parkinson's disease (PD) and Dementia with Lewy bodies (DLB) are characterized by the simultaneous...
Several degenerative brain disorders such as Alzheimer's disease (AD), Parkinson's disease (PD) and Dementia with Lewy bodies (DLB) are characterized by the simultaneous appearance of amyloid-β (Aβ) and α-synuclein (α-syn) pathologies and symptoms that are similar, making it difficult to differentiate between these diseases. Until now, an accurate diagnosis can only be made by postmortem analysis. Furthermore, the role of α-syn in Aβ aggregation and the arising characteristic olfactory impairments observed during the progression of these diseases is still not well understood. Therefore, we assessed Aβ load in olfactory bulbs of APP-transgenic mice expressing APP695 and PSEN1 under the control of the neuron-specific Thy-1 promoter (referred to here as APPPS1) and APPPS1 mice co-expressing SNCA (referred to here as APPPS1 × [A30P]aSYN). Furthermore, the olfactory capacity of these mice was evaluated in the buried food and olfactory avoidance test. Our results demonstrate an age-dependent increase in Aβ load in the olfactory bulb of APP-transgenic mice that go along with exacerbated olfactory performance. Our study provides clear evidence that the presence of α-syn significantly diminished the endogenous and seed-induced Aβ deposits and significantly ameliorated olfactory dysfunction in APPPS1 × [A30P]aSYN mice.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Disease Models, Animal; Mice; Mice, Transgenic; Olfactory Bulb; Synucleinopathies; alpha-Synuclein
PubMed: 34713522
DOI: 10.1111/bpa.13032 -
The Journal of Neuroscience : the... May 2022Odors are transported by turbulent air currents, creating complex temporal fluctuations in odor concentration that provide a potentially informative stimulus dimension....
Odors are transported by turbulent air currents, creating complex temporal fluctuations in odor concentration that provide a potentially informative stimulus dimension. We have shown that mice are able to discriminate odor stimuli based on their temporal structure, indicating that information contained in the temporal structure of odor plumes can be extracted by the mouse olfactory system. Here, using extracellular and intracellular electrophysiological recordings, we show that mitral cells (MCs) and tufted cells (TCs) of the male C57BL/6 mouse olfactory bulb can encode the dominant temporal frequencies present in odor stimuli up to at least 20 Hz. A substantial population of cell-odor pairs showed significant coupling of their subthreshold membrane potential with the odor stimulus at both 2 Hz (29/70) and the suprasniff frequency 20 Hz (24/70). Furthermore, mitral/tufted cells (M/TCs) show differential coupling of their membrane potential to odor concentration fluctuations with tufted cells coupling more strongly for the 20 Hz stimulation. Frequency coupling was always observed to be invariant to odor identity, and M/TCs that coupled well to a mixture also coupled to at least one of the components of the mixture. Interestingly, pharmacological blocking of the inhibitory circuitry strongly modulated frequency coupling of cell-odor pairs at both 2 Hz (10/15) and 20 Hz (9/15). These results provide insight into how both cellular and circuit properties contribute to the encoding of temporal odor features in the mouse olfactory bulb. Odors in the natural environment have a strong temporal structure that can be extracted and used by mice in their behavior. Here, using extracellular and intracellular electrophysiological techniques, we show that the projection neurons in the olfactory bulb can encode and couple to the dominant frequency present in an odor stimulus. Furthermore, frequency coupling was observed to be differential between mitral and tufted cells and was odor invariant but strongly modulated by local inhibitory circuits. In summary, this study provides insight into how both cellular and circuit properties modulate encoding of odor temporal features in the mouse olfactory bulb.
Topics: Animals; Interneurons; Male; Mice; Mice, Inbred C57BL; Neurons; Odorants; Olfactory Bulb; Smell
PubMed: 35440491
DOI: 10.1523/JNEUROSCI.1422-21.2022 -
Neuroradiology Jan 2023The neurotropism of SARS-CoV-2 and the consequential damage to the olfactory system have been proposed as one of the possible underlying causes of olfactory dysfunction... (Meta-Analysis)
Meta-Analysis
PURPOSE
The neurotropism of SARS-CoV-2 and the consequential damage to the olfactory system have been proposed as one of the possible underlying causes of olfactory dysfunction in COVID-19. We aimed to aggregate the results of the studies which reported imaging of the olfactory system of patients with COVID-19 versus controls.
METHODS
PubMed and EMBASE were searched to identify relevant literature reporting the structural imaging characteristics of the olfactory bulb (OB), olfactory cleft, olfactory sulcus (OS), or olfactory tract in COVID-19 patients. Hedge's g and weighted mean difference were used as a measure of effect size. Quality assessment, subgroup analyses, meta-regression, and sensitivity analysis were also conducted.
RESULTS
Ten studies were included in the qualitative synthesis, out of which seven studies with 183 cases with COVID-19 and 308 controls without COVID-19 were enrolled in the quantitative synthesis. No significant differences were detected in analyses of right OB volume and left OB volume. Likewise, right OS depth and left OS depth were also not significantly different in COVID-19 cases compared to non-COVID-19 controls. Also, we performed subgroup analysis, meta-regression, and sensitivity analysis to investigate the potential effect of confounding moderators.
CONCLUSION
The findings of this review did not confirm alterations in structural imaging of the olfactory system, including OB volume and OS depth by Covid-19 which is consistent with the results of recent histopathological evaluations.
Topics: Humans; Olfaction Disorders; COVID-19; SARS-CoV-2; Magnetic Resonance Imaging; Olfactory Bulb
PubMed: 35843987
DOI: 10.1007/s00234-022-03014-8 -
International Journal of Molecular... Dec 2021Particulate matter (PM) is an environmental hazard that is associated with various human health risks. The olfactory system is directly exposed to PM; therefore, the...
Particulate matter (PM) is an environmental hazard that is associated with various human health risks. The olfactory system is directly exposed to PM; therefore, the influence of PM exposure on olfactory function must be investigated. In this study, we propose a zebrafish olfactory model to evaluate the effects of exposure to diesel particulate matter (DPM), which was labeled Korean diesel particulate matter (KDP20). KDP20 comprises heavy metals and polycyclic aromatic hydrocarbons (PAHs). KDP20 exposed olfactory organs exhibited reduced cilia and damaged epithelium. Olfactory dysfunction was confirmed using an odor-mediated behavior test. Furthermore, the olfactory damage was analyzed using Alcian blue and anti-calretinin staining. KDP20 exposed olfactory organs exhibited histological damages, such as increased goblet cells, decreased cell density, and calretinin level. Quantitative real-time polymerase chain reaction (qRT-PCR) revealed that PAHs exposure related genes ( and ) were upregulated. Reactive oxidation stress (ROS) () and inflammation () related genes were upregulated. Furthermore, olfactory sensory neuron (OSN) related genes ( and ) were downregulated. In conclusion, KDP20 exposure induced dysfunction of the olfactory system. Additionally, the zebrafish olfactory system exhibited a regenerative capacity with recovery conditions. Thus, this model may be used in future investigating PM-related diseases.
Topics: Aging; Animals; Behavior, Animal; Calbindin 2; Dynamic Light Scattering; Odorants; Olfactory Bulb; Particle Size; Particulate Matter; Spectrometry, X-Ray Emission; Survival Analysis; Vehicle Emissions; Zebrafish
PubMed: 35008830
DOI: 10.3390/ijms23010407 -
Frontiers in Neural Circuits 2024Various mammals have shown that sensory stimulation plays a crucial role in regulating the development of diverse structures, such as the olfactory bulb (OB), cerebral... (Review)
Review
Various mammals have shown that sensory stimulation plays a crucial role in regulating the development of diverse structures, such as the olfactory bulb (OB), cerebral cortex, hippocampus, and retina. In the OB, the dendritic development of excitatory projection neurons like mitral/tufted cells is influenced by olfactory experiences. Odor stimulation is also essential for the dendritic development of inhibitory OB interneurons, such as granule and periglomerular cells, which are continuously produced in the ventricular-subventricular zone throughout life. Based on the morphological and molecular features, OB interneurons are classified into several subtypes. The role for each interneuron subtype in the control of olfactory behavior remains poorly understood due to lack of each specific marker. Among the several OB interneuron subtypes, a specific granule cell subtype, which expresses the oncofetal trophoblast glycoprotein (Tpbg or 5T4) gene, has been reported to be required for odor detection and discrimination behavior. This review will primarily focus on elucidating the contribution of different granule cell subtypes, including the Tpbg/5T4 subtype, to olfactory processing and behavior during the embryonic and adult stages.
Topics: Animals; Interneurons; Olfactory Bulb; Humans; Neurogenesis
PubMed: 38933598
DOI: 10.3389/fncir.2024.1427378 -
Cerebral Cortex (New York, N.Y. : 1991) Feb 2022The olfactory bulb (OB) delivers sensory information to the piriform cortex (PC) and other components of the olfactory system. OB-PC synapses have been reported to...
The olfactory bulb (OB) delivers sensory information to the piriform cortex (PC) and other components of the olfactory system. OB-PC synapses have been reported to express short-lasting forms of synaptic plasticity, whereas long-term potentiation (LTP) of the anterior PC (aPC) occurs predominantly by activating inputs from the prefrontal cortex. This suggests that brain regions outside the olfactory system may contribute to olfactory information processing and storage. Here, we compared functional magnetic resonance imaging BOLD responses triggered during 20 or 100 Hz stimulation of the OB. We detected BOLD signal increases in the anterior olfactory nucleus (AON), PC and entorhinal cortex, nucleus accumbens, dorsal striatum, ventral diagonal band of Broca, prelimbic-infralimbic cortex (PrL-IL), dorsal medial prefrontal cortex, and basolateral amygdala. Significantly stronger BOLD responses occurred in the PrL-IL, PC, and AON during 100 Hz compared with 20 Hz OB stimulation. LTP in the aPC was concomitantly induced by 100 Hz stimulation. Furthermore, 100 Hz stimulation triggered significant nuclear immediate early gene expression in aPC, AON, and PrL-IL. The involvement of the PrL-IL in this process is consistent with its putative involvement in modulating behavioral responses to odor experience. Furthermore, these results indicate that OB-mediated information storage by the aPC is embedded in a connectome that supports valence evaluation.
Topics: Information Storage and Retrieval; Neuronal Plasticity; Olfactory Bulb; Piriform Cortex; Smell
PubMed: 34379749
DOI: 10.1093/cercor/bhab226 -
Folia Morphologica 2021The aim of this study was to determine the normal reference values for olfactory sulcus depth, olfactory tract length and olfactory bulb volume in the paediatric...
BACKGROUND
The aim of this study was to determine the normal reference values for olfactory sulcus depth, olfactory tract length and olfactory bulb volume in the paediatric population with routine magnetic resonance imaging (MRI) and determine the relationship, if any, between these values and patient sex and age.
MATERIALS AND METHODS
Ninety patients with a median age of 8 years (age range: 3-17 years), consisting of 45 males and 45 females with normal brain MRI scans were evaluated. The patients were divided into three subgroups based on age range, with n = 30 per subgroup; group 1: young children (3-6 years), group 2: children (7-11 years) and group 3: adolescents (12-17 years). In the cranial MRI examination of all groups, the right, left and total olfactory bulb volume values were measured in mm3, the right and left olfactory tract length values and the right and left olfactory sulcus depth values were calculated manually in mm. Demographic data including sex and age were recorded.
RESULTS
There was no significant difference between the age groups in terms of sex. Right-left olfactory sulcus depth; right-left olfactory tract length and right-left total olfactory bulb volume values increased significantly when they are compared in terms of age groups (p < 0.0001, = 0.028; < 0.0001, < 0.0001; < 0.0001, < 0.0001; < 0.0001, respectively). There was no significant difference between right and left olfactory tract length and olfactory bulb volumes in all groups (p = 0.792 and p = 0.478), but the right olfactory sulcus depth was significantly larger than the left (p = 0.003).
CONCLUSIONS
Especially as the age progresses, olfactory tract length and olfactory bulb volume dimensions of olfactory nerve and olfactory sulcus depth should be checked during diagnosis of respective illnesses in paediatric population.
Topics: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Olfaction Disorders; Olfactory Bulb; Prefrontal Cortex
PubMed: 33084007
DOI: 10.5603/FM.a2020.0125 -
Neuroscience Jan 2020Kainate receptors (KARs) are glutamate receptors with ionotropic and metabotropic activity composed of the GluK1-GluK5 subunits. We previously reported that KARs...
Kainate receptors (KARs) are glutamate receptors with ionotropic and metabotropic activity composed of the GluK1-GluK5 subunits. We previously reported that KARs modulate excitatory and inhibitory transmission in the olfactory bulb (OB). Zinc, which is highly concentrated in the OB, also appears to modulate OB synaptic transmission via actions at other ionotropic glutamate receptors (i.e., AMPA, NMDA). However, few reports of effects of zinc on recombinant and/or native KARs exist and none have involved the OB. In the present study, we investigated the effects of exogenously applied zinc on OB KARs expressed by mitral/tufted (M/T) cells. We found that 100 µM zinc inhibits currents evoked by various combinations of KAR agonists (kainate or SYM 2081) and the AMPA receptor antagonist SYM 2206. The greatest degree of zinc-mediated inhibition was observed with coapplication of zinc with the GluK1- and GluK2-preferring agonist SYM 2081 plus SYM 2206. This finding is consistent with prior reports of zinc's inhibitory effects on some recombinant (homomeric GluK1 and GluK2 and heteromeric GluK2/GluK4 and GluK2/GluK5) KARs, although potentiation of other (GluK3, GluK2/3) KARs has also been described. It is also of potential importance given our previously reported molecular data suggesting that OB neurons express relatively high levels of GluK1 and GluK2. Our present findings suggest that a physiologically relevant concentration of zinc modulates KARs expressed by M/T cells. As M/T cells are targets of zinc-containing olfactory sensory neurons, synaptically released zinc may influence odor information-encoding synaptic circuits in the OB via actions at KARs.
Topics: Animals; Glutamic Acid; Neurons; Olfactory Bulb; Protein Multimerization; Protein Subunits; Rats, Sprague-Dawley; Receptors, Kainic Acid; Synapses; Synaptic Transmission; Zinc
PubMed: 31874243
DOI: 10.1016/j.neuroscience.2019.11.041