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Sample records for olfactory bulb accelerates

  1. Disinhibition of olfactory bulb granule cells accelerates odour discrimination in mice

    PubMed Central

    Nunes, Daniel; Kuner, Thomas

    2015-01-01

    Granule cells are the dominant cell type of the olfactory bulb inhibiting mitral and tufted cells via dendrodendritic synapses; yet the factors regulating the strength of their inhibitory output, and, therefore, their impact on odour discrimination, remain unknown. Here we show that GABAAR β3-subunits are distributed in a somatodendritic pattern, mostly sparing the large granule cell spines also known as gemmules. Granule cell-selective deletion of β3-subunits nearly abolishes spontaneous and muscimol-induced currents mediated by GABAA receptors in granule cells, yet recurrent inhibition of mitral cells is strongly enhanced. Mice with disinhibited granule cells require less time to discriminate both dissimilar as well as highly similar odourants, while discrimination learning remains unaffected. Hence, granule cells are controlled by an inhibitory drive that in turn tunes mitral cell inhibition. As a consequence, the olfactory bulb inhibitory network adjusts the speed of early sensory processing. PMID:26592770

  2. Centrifugal innervation of the mammalian olfactory bulb.

    PubMed

    Matsutani, Shinji; Yamamoto, Noboru

    2008-12-01

    Although it has been known for decades that the mammalian olfactory bulb receives a substantial number of centrifugal inputs from other regions of the brain, relatively few data have been available on the function of the centrifugal olfactory system. Knowing the role of the centrifugal projection and how it works is of critical importance to fully understanding olfaction. The centrifugal fibers can be classified into two groups, a group that release neuromodulators, such as noradrenaline, serotonin, or acetylcholine, and a group originating in the olfactory cortex. Accumulating evidence suggests that centrifugal neuromodulatory inputs are associated with acquisition of odor memory. Because the distribution of the terminals on these fibers is diffuse and widespread, the neuromodulatory inputs must affect diverse subsets of bulbar neurons at the same time. In contrast, knowledge of the role of centrifugal fibers from the olfactory cortical areas is limited. Judging from recent morphological evidence, these fibers may modify the activity of neurons located in sparse and discrete loci in the olfactory bulb. Given the modular organization of the olfactory bulb, centrifugal fibers from the olfactory cortex may help coordinate the activities of restricted subsets of neurons belonging to distinct functional modules in an odor-specific manner. Because the olfactory cortex receives inputs from limbic and neocortical areas in addition to inputs from the bulb, the centrifugal inputs from the cortex can modulate odor processing in the bulb in response to non-olfactory as well as olfactory cues.

  3. Olfactory bulb encoding during learning under anesthesia

    PubMed Central

    Nicol, Alister U.; Sanchez-Andrade, Gabriela; Collado, Paloma; Segonds-Pichon, Anne; Kendrick, Keith M.

    2014-01-01

    Neural plasticity changes within the olfactory bulb are important for olfactory learning, although how neural encoding changes support new associations with specific odors and whether they can be investigated under anesthesia, remain unclear. Using the social transmission of food preference olfactory learning paradigm in mice in conjunction with in vivo microdialysis sampling we have shown firstly that a learned preference for a scented food odor smelled on the breath of a demonstrator animal occurs under isofluorane anesthesia. Furthermore, subsequent exposure to this cued odor under anesthesia promotes the same pattern of increased release of glutamate and gamma-aminobutyric acid (GABA) in the olfactory bulb as previously found in conscious animals following olfactory learning, and evoked GABA release was positively correlated with the amount of scented food eaten. In a second experiment, multiarray (24 electrodes) electrophysiological recordings were made from olfactory bulb mitral cells under isofluorane anesthesia before, during and after a novel scented food odor was paired with carbon disulfide. Results showed significant increases in overall firing frequency to the cued-odor during and after learning and decreases in response to an uncued odor. Analysis of patterns of changes in individual neurons revealed that a substantial proportion (>50%) of them significantly changed their response profiles during and after learning with most of those previously inhibited becoming excited. A large number of cells exhibiting no response to the odors prior to learning were either excited or inhibited afterwards. With the uncued odor many previously responsive cells became unresponsive or inhibited. Learning associated changes only occurred in the posterior part of the olfactory bulb. Thus olfactory learning under anesthesia promotes extensive, but spatially distinct, changes in mitral cell networks to both cued and uncued odors as well as in evoked glutamate and GABA

  4. Olfactory Perceptual Learning Requires Action of Noradrenaline in the Olfactory Bulb: Comparison with Olfactory Associative Learning

    ERIC Educational Resources Information Center

    Vinera, Jennifer; Kermen, Florence; Sacquet, Joëlle; Didier, Anne; Mandairon, Nathalie; Richard, Marion

    2015-01-01

    Noradrenaline contributes to olfactory-guided behaviors but its role in olfactory learning during adulthood is poorly documented. We investigated its implication in olfactory associative and perceptual learning using local infusion of mixed a1-ß adrenergic receptor antagonist (labetalol) in the adult mouse olfactory bulb. We reported that…

  5. Differential Muscarinic Modulation in the Olfactory Bulb

    PubMed Central

    Smith, Richard S.; Hu, Ruilong; DeSouza, Andre; Eberly, Christian L.; Krahe, Krista; Chan, Wilson

    2015-01-01

    Neuromodulation of olfactory circuits by acetylcholine (ACh) plays an important role in odor discrimination and learning. Early processing of chemosensory signals occurs in two functionally and anatomically distinct regions, the main and accessory olfactory bulbs (MOB and AOB), which receive extensive cholinergic input from the basal forebrain. Here, we explore the regulation of AOB and MOB circuits by ACh, and how cholinergic modulation influences olfactory-mediated behaviors in mice. Surprisingly, despite the presence of a conserved circuit, activation of muscarinic ACh receptors revealed marked differences in cholinergic modulation of output neurons: excitation in the AOB and inhibition in the MOB. Granule cells (GCs), the most abundant intrinsic neuron in the OB, also exhibited a complex muscarinic response. While GCs in the AOB were excited, MOB GCs exhibited a dual muscarinic action in the form of a hyperpolarization and an increase in excitability uncovered by cell depolarization. Furthermore, ACh influenced the input–output relationship of mitral cells in the AOB and MOB differently showing a net effect on gain in mitral cells of the MOB, but not in the AOB. Interestingly, despite the striking differences in neuromodulatory actions on output neurons, chemogenetic inhibition of cholinergic neurons produced similar perturbations in olfactory behaviors mediated by these two regions. Decreasing ACh in the OB disrupted the natural discrimination of molecularly related odors and the natural investigation of odors associated with social behaviors. Thus, the distinct neuromodulation by ACh in these circuits could underlie different solutions to the processing of general odors and semiochemicals, and the diverse olfactory behaviors they trigger. SIGNIFICANCE STATEMENT State-dependent cholinergic modulation of brain circuits is critical for several high-level cognitive functions, including attention and memory. Here, we provide new evidence that cholinergic

  6. Role of Centrifugal Projections to the Olfactory Bulb in Olfactory Processing

    ERIC Educational Resources Information Center

    Kiselycznyk, Carly L.; Zhang, Steven; Linster, Christine

    2006-01-01

    While there is evidence that feedback projections from cortical and neuromodulatory structures to the olfactory bulb are crucial for maintaining the oscillatory dynamics of olfactory bulb processing, it is not clear how changes in dynamics are related to odor perception. Using electrical lesions of the olfactory peduncle, sparing output from the…

  7. Olfactory dysfunction, olfactory bulb pathology and urban air pollution

    PubMed Central

    Calderón-Garcidueñas, Lilian; Franco-Lira, Maricela; Henríquez-Roldán, Carlos; Osnaya, Norma; González-Maciel, Angelica; Reynoso-Robles, Rafael; Villarreal-Calderon, Rafael; Herritt, Lou; Brooks, Diane; Keefe, Sheyla; Palacios-Moreno, Juan; Villarreal-Calderon, Rodolfo; Torres-Jardón, Ricardo; Medina-Cortina, Humberto; Delgado-Chávez, Ricardo; Aiello-Mora, Mario; Maronpot, Robert R.; Doty, Richard L

    2010-01-01

    Mexico City (MC) residents are exposed to severe air pollution and exhibit olfactory bulb inflammation. We compared the olfactory function of individuals living under conditions of extreme air pollution to that of controls from a relatively clean environment and explore associations between olfaction scores, apolipoprotein E (APOE) status, and pollution exposure. The olfactory bulbs (OBs) of 35 MC and 9 controls 20.8 ± 8.5 y were assessed by light and electron microscopy. The University of Pennsylvania Smell Identification Test (UPSIT) was administered to 62 MC / 25 controls 21.2 ±2.7 y. MC subjects had significantly lower UPSIT scores: 34.24 ± 0.42 versus controls 35.76 ± 0.40, p=0.03. Olfaction deficits were present in 35.5% MC and 12% of controls. MC APOE ε 4 carriers failed 2.4 ± 0.54 items in the 10-item smell identification scale from the UPSIT related to Alzheimer's disease, while APOE 2/3 and 3/3 subjects failed 1.36 ± 0.16 items, p = 0.01. MC residents exhibited OB endothelial hyperplasia, neuronal accumulation of particles (2/35), and immunoreactivity to beta amyloid βA42 (29/35) and/or α-synuclein (4/35) in neurons, glial cells and/or blood vessels. Ultrafine particles were present in OBs endothelial cytoplasm and basement membranes. Control OBs were unremarkable. Air pollution exposure is associated with olfactory dysfunction and OB pathology, APOE 4 may confer greater susceptibility to such abnormalities, and ultrafine particles could play a key role in the OB pathology. This study contributes to our understanding of the influences of air pollution on olfaction and its potential contribution to neurodegeneration. PMID:19297138

  8. Topographical representation of odor hedonics in the olfactory bulb.

    PubMed

    Kermen, Florence; Midroit, Maëllie; Kuczewski, Nicola; Forest, Jérémy; Thévenet, Marc; Sacquet, Joëlle; Benetollo, Claire; Richard, Marion; Didier, Anne; Mandairon, Nathalie

    2016-07-01

    Hedonic value is a dominant aspect of olfactory perception. Using optogenetic manipulation in freely behaving mice paired with immediate early gene mapping, we demonstrate that hedonic information is represented along the antero-posterior axis of the ventral olfactory bulb. Using this representation, we show that the degree of attractiveness of odors can be bidirectionally modulated by local manipulation of the olfactory bulb's neural networks in freely behaving mice. PMID:27273767

  9. Voltage-Dependent Intrinsic Bursting in Olfactory Bulb Golgi Cells

    ERIC Educational Resources Information Center

    Pressler, R. Todd; Rozman, Peter A.; Strowbridge, Ben W.

    2013-01-01

    In the mammalian olfactory bulb (OB), local synaptic circuits modulate the evolving pattern of activity in mitral and tufted cells following olfactory sensory stimulation. GABAergic granule cells, the most numerous interneuron subtype in this brain region, have been extensively studied. However, classic studies using Golgi staining methods…

  10. Integrating temperature with odor processing in the olfactory bulb.

    PubMed

    Kludt, Eugen; Okom, Camille; Brinkmann, Alexander; Schild, Detlev

    2015-05-20

    Temperature perception has long been classified as a somesthetic function solely. However, in recent years several studies brought evidence that temperature perception also takes place in the olfactory system of rodents. Temperature has been described as an effective stimulus for sensory neurons of the Grueneberg ganglion located at the entrance of the nose. Here, we investigate whether a neuronal trace of temperature stimulation can be observed in the glomeruli and mitral cells of the olfactory bulb, using calcium imaging and fast line-scanning microscopy. We show in the Xenopus tadpole system that the γ-glomerulus, which receives input from olfactory neurons, is highly sensitive to temperature drops at the olfactory epithelium. We observed that thermo-induced activity in the γ-glomerulus is conveyed to the mitral cells innervating this specific neuropil. Surprisingly, a substantial number of thermosensitive mitral cells were also chemosensitive. Moreover, we report another unique feature of the γ-glomerulus: it receives ipsilateral and contralateral afferents. The latter fibers pass through the contralateral bulb, cross the anterior commissure, and then run to the ipsilateral olfactory bulb, where they target the γ-glomerulus. Temperature drops at the contralateral olfactory epithelium also induced responses in the γ-glomerulus and in mitral cells. Temperature thus appears to be a relevant physiological input to the Xenopus olfactory system. Each olfactory bulb integrates and codes temperature signals originating from receptor neurons of the ipsilateral and contralateral nasal cavities. Finally, temperature and chemical information is processed in shared cellular networks.

  11. Cytokines and olfactory bulb microglia in response to bacterial challenge in the compromised primary olfactory pathway

    PubMed Central

    2012-01-01

    Background The primary olfactory pathway is a potential route through which microorganisms from the periphery could potentially access the central nervous system. Our previous studies demonstrated that if the olfactory epithelium was damaged, bacteria administered into the nasal cavity induced nitric oxide production in olfactory ensheathing cells. This study investigates the cytokine profile of olfactory tissues as a consequence of bacterial challenge and establishes whether or not the bacteria are able to reach the olfactory bulb in the central nervous system. Methods The olfactory epithelium of C57BL/6 mice was damaged by unilateral Triton X-100 nasal washing, and Staphylococcus aureus was administered ipsilaterally 4 days later. Olfactory mucosa and bulb were harvested 6 h, 24 h and 5 days after inoculation and their cytokine profile compared to control tissues. The fate of S. aureus and the response of bulbar microglia were examined using fluorescence microscopy and transmission electron microscopy. Results In the olfactory mucosa, administered S. aureus was present in supporting cells of the olfactory epithelium, and macrophages and olfactory nerve bundles in the lamina propria. Fluorescein isothiocyanate-conjugated S. aureus was observed within the olfactory mucosa and bulb 6 h after inoculation, but remained restricted to the peripheral layers up to 5 days later. At the 24-h time point, the level of interleukin-6 (IL-6) and tumour necrosis factor-α in the compromised olfactory tissues challenged with bacteria (12,466 ± 956 pg/ml and 552 ± 193 pg/ml, respectively) was significantly higher than that in compromised olfactory tissues alone (6,092 ± 1,403 pg/ml and 80 ± 2 pg/ml, respectively). Immunohistochemistry confirmed that IL-6 was present in several cell types including olfactory ensheathing cells and mitral cells of the olfactory bulb. Concurrently, there was a 4.4-, 4.5- and 2.8-fold increase in the density of i

  12. Broadcasting of cortical activity to the olfactory bulb.

    PubMed

    Boyd, Alison M; Kato, Hiroyuki K; Komiyama, Takaki; Isaacson, Jeffry S

    2015-02-24

    Odor representations are initially formed in the olfactory bulb, which contains a topographic glomerular map of odor molecular features. The bulb transmits sensory information directly to piriform cortex, where it is encoded by distributed ensembles of pyramidal cells without spatial order. Intriguingly, piriform cortex pyramidal cells project back to the bulb, but the information contained in this feedback projection is unknown. Here, we use imaging in awake mice to directly monitor activity in the presynaptic boutons of cortical feedback fibers. We show that the cortex provides the bulb with a rich array of information for any individual odor and that cortical feedback is dependent on brain state. In contrast to the stereotyped, spatial arrangement of olfactory bulb glomeruli, cortical inputs tuned to different odors commingle and indiscriminately target individual glomerular channels. Thus, the cortex modulates early odor representations by broadcasting sensory information diffusely onto spatially ordered bulbar circuits.

  13. Broadcasting of cortical activity to the olfactory bulb.

    PubMed

    Boyd, Alison M; Kato, Hiroyuki K; Komiyama, Takaki; Isaacson, Jeffry S

    2015-02-24

    Odor representations are initially formed in the olfactory bulb, which contains a topographic glomerular map of odor molecular features. The bulb transmits sensory information directly to piriform cortex, where it is encoded by distributed ensembles of pyramidal cells without spatial order. Intriguingly, piriform cortex pyramidal cells project back to the bulb, but the information contained in this feedback projection is unknown. Here, we use imaging in awake mice to directly monitor activity in the presynaptic boutons of cortical feedback fibers. We show that the cortex provides the bulb with a rich array of information for any individual odor and that cortical feedback is dependent on brain state. In contrast to the stereotyped, spatial arrangement of olfactory bulb glomeruli, cortical inputs tuned to different odors commingle and indiscriminately target individual glomerular channels. Thus, the cortex modulates early odor representations by broadcasting sensory information diffusely onto spatially ordered bulbar circuits. PMID:25704808

  14. Parvalbumin-expressing interneurons linearly control olfactory bulb output

    PubMed Central

    Kato, Hiroyuki K.; Gillet, Shea N.; Peters, Andrew J.; Isaacson, Jeffry S.; Komiyama, Takaki

    2013-01-01

    SUMMARY In the olfactory bulb, odor representations by principal mitral cells are modulated by local inhibitory circuits. While dendrodendritic synapses between mitral and granule cells are typically thought to be a major source of this modulation, the contributions of other inhibitory neurons remain unclear. Here we demonstrate the functional properties of olfactory bulb parvalbumin-expressing interneurons (PV cells) and identify their important role in odor coding. Using paired recordings, we find that PV cells form reciprocal connections with the majority of nearby mitral cells, in contrast to the sparse connectivity between mitral and granule cells. In vivo calcium imaging in awake mice reveals that PV cells are broadly tuned to odors. Furthermore, selective PV cell inactivation enhances mitral cell responses in a linear fashion while maintaining mitral cell odor preferences. Thus, dense connections between mitral and PV cells underlie an inhibitory circuit poised to modulate the gain of olfactory bulb output. PMID:24239124

  15. Parvalbumin-expressing interneurons linearly control olfactory bulb output.

    PubMed

    Kato, Hiroyuki K; Gillet, Shea N; Peters, Andrew J; Isaacson, Jeffry S; Komiyama, Takaki

    2013-12-01

    In the olfactory bulb, odor representations by principal mitral cells are modulated by local inhibitory circuits. While dendrodendritic synapses between mitral and granule cells are typically thought to be a major source of this modulation, the contributions of other inhibitory neurons remain unclear. Here we demonstrate the functional properties of olfactory bulb parvalbumin-expressing interneurons (PV cells) and identify their important role in odor coding. Using paired recordings, we find that PV cells form reciprocal connections with the majority of nearby mitral cells, in contrast to the sparse connectivity between mitral and granule cells. In vivo calcium imaging in awake mice reveals that PV cells are broadly tuned to odors. Furthermore, selective PV cell inactivation enhances mitral cell responses in a linear fashion while maintaining mitral cell odor preferences. Thus, dense connections between mitral and PV cells underlie an inhibitory circuit poised to modulate the gain of olfactory bulb output. PMID:24239124

  16. Electrophysiological differentiation of new neurons in the olfactory bulb.

    PubMed

    Belluzzi, Ottorino; Benedusi, Mascia; Ackman, James; LoTurco, Joseph J

    2003-11-12

    The subventricular zone produces neuroblasts that migrate to the olfactory bulb (OB) and differentiate into interneurons throughout postnatal life (Altman and Das, 1966; Hinds, 1968; Altman, 1969; Kishi et al., 1990; Luskin, 1993; Lois and Alvarez-Buylla, 1994). Although such postnatally generated interneurons have been characterized morphologically, their physiological differentiation has not been thoroughly described. Combining retroviral-mediated labeling of newly generated neurons with patch-clamp electrophysiology, we demonstrated that soon after new cells enter the layers of the olfactory bulb, they display voltage-dependent currents typical of more mature neurons. We also show that these "newcomers" express functional GABA and glutamate receptor channels, respond synaptically to stimulation of the olfactory nerve, and may establish both axodendritic and dendrodendritic synaptic contacts within the olfactory bulb. These data provide a basic description of the physiology of newly generated cells in the OB and show that such new cells are functional neurons that synaptically integrate into olfactory bulb circuitry soon after their arrival.

  17. Construction of odor representations by olfactory bulb microcircuits.

    PubMed

    Cleland, Thomas A

    2014-01-01

    Like other sensory systems, the olfactory system transduces specific features of the external environment and must construct an organized sensory representation from these highly fragmented inputs. As with these other systems, this representation is not accurate per se, but is constructed for utility, and emphasizes certain, presumably useful, features over others. I here describe the cellular and circuit mechanisms of the peripheral olfactory system that underlie this process of sensory construction, emphasizing the distinct architectures and properties of the two prominent computational layers in the olfactory bulb. Notably, while the olfactory system solves essentially similar conceptual problems to other sensory systems, such as contrast enhancement, activity normalization, and extending dynamic range, its peculiarities often require qualitatively different computational algorithms than are deployed in other sensory modalities. In particular, the olfactory modality is intrinsically high dimensional, and lacks a simple, externally defined basis analogous to wavelength or pitch on which elemental odor stimuli can be quantitatively compared. Accordingly, the quantitative similarities of the receptive fields of different odorant receptors (ORs) vary according to the statistics of the odor environment. To resolve these unusual challenges, the olfactory bulb appears to utilize unique nontopographical computations and intrinsic learning mechanisms to perform the necessary high-dimensional, similarity-dependent computations. In sum, the early olfactory system implements a coordinated set of early sensory transformations directly analogous to those in other sensory systems, but accomplishes these with unique circuit architectures adapted to the properties of the olfactory modality.

  18. Notch1 activity in the olfactory bulb is odour-dependent and contributes to olfactory behaviour.

    PubMed

    Brai, Emanuele; Marathe, Swananda; Zentilin, Lorena; Giacca, Mauro; Nimpf, Johannes; Kretz, Robert; Scotti, Alessandra; Alberi, Lavinia

    2014-11-01

    Notch signalling plays an important role in synaptic plasticity, learning and memory functions in both Drosophila and rodents. In this paper, we report that this feature is not restricted to hippocampal networks but also involves the olfactory bulb (OB). Odour discrimination and olfactory learning in rodents are essential for survival. Notch1 expression is enriched in mitral cells of the mouse OB. These principal neurons are responsive to specific input odorants and relay the signal to the olfactory cortex. Olfactory stimulation activates a subset of mitral cells, which show an increase in Notch activity. In Notch1cKOKln mice, the loss of Notch1 in mitral cells affects the magnitude of the neuronal response to olfactory stimuli. In addition, Notch1cKOKln mice display reduced olfactory aversion to propionic acid as compared to wildtype controls. This indicates, for the first time, that Notch1 is involved in olfactory processing and may contribute to olfactory behaviour.

  19. Neuronal circuits and computations: pattern decorrelation in the olfactory bulb.

    PubMed

    Friedrich, Rainer W; Wiechert, Martin T

    2014-08-01

    Neuronal circuits in the olfactory bulb transform odor-evoked activity patterns across the input channels, the olfactory glomeruli, into distributed activity patterns across the output neurons, the mitral cells. One computation associated with this transformation is a decorrelation of activity patterns representing similar odors. Such a decorrelation has various benefits for the classification and storage of information by associative networks in higher brain areas. Experimental results from adult zebrafish show that pattern decorrelation involves a redistribution of activity across the population of mitral cells. These observations imply that pattern decorrelation cannot be explained by a global scaling mechanism but that it depends on interactions between distinct subsets of neurons in the network. This article reviews insights into the network mechanism underlying pattern decorrelation and discusses recent results that link pattern decorrelation in the olfactory bulb to odor discrimination behavior.

  20. Relation of the volume of the olfactory bulb to psychophysical measures of olfactory function.

    PubMed

    Mazal, Patricia Portillo; Haehner, Antje; Hummel, Thomas

    2016-01-01

    The aim of this review is to investigate whether changes in olfactory bulb volume relate to changes in specific olfactory functions. We studied currently available peer-reviewed articles on the volume of the human olfactory bulb that also included a psychophysical measure of olfactory function. In the present review, we observed a very clear and consistent correlation between general olfactory function and olfactory bulb (OB) volume. We were not able to find a clear relationship between a specific smell component and OB volume, even when analyzing pathologic conditions separately. In some cases, changes were observed for different subtests, but these changes did not significantly correlate with OB volume or had only a borderline correlation. In other cases, we found contradictory data. Several factors may contribute to the difficulties in finding correlations with the different components of smell: (1) the OB volume may be influenced by information from olfactory receptor neurons (bottom-up effect), information from central nervous system (top-down effect) and by direct damage; (2) most pathologic conditions affect more than one area of the olfactory pathway; (3) small sample sizes of hyposmic subjects were used. We believe that it is necessary to do further studies with larger numbers of subjects to answer the currently investigated question.

  1. Massive normalization of olfactory bulb output in mice with a 'monoclonal nose'.

    PubMed

    Roland, Benjamin; Jordan, Rebecca; Sosulski, Dara L; Diodato, Assunta; Fukunaga, Izumi; Wickersham, Ian; Franks, Kevin M; Schaefer, Andreas T; Fleischmann, Alexander

    2016-01-01

    Perturbations in neural circuits can provide mechanistic understanding of the neural correlates of behavior. In M71 transgenic mice with a "monoclonal nose", glomerular input patterns in the olfactory bulb are massively perturbed and olfactory behaviors are altered. To gain insights into how olfactory circuits can process such degraded inputs we characterized odor-evoked responses of olfactory bulb mitral cells and interneurons. Surprisingly, calcium imaging experiments reveal that mitral cell responses in M71 transgenic mice are largely normal, highlighting a remarkable capacity of olfactory circuits to normalize sensory input. In vivo whole cell recordings suggest that feedforward inhibition from olfactory bulb periglomerular cells can mediate this signal normalization. Together, our results identify inhibitory circuits in the olfactory bulb as a mechanistic basis for many of the behavioral phenotypes of mice with a "monoclonal nose" and highlight how substantially degraded odor input can be transformed to yield meaningful olfactory bulb output. PMID:27177421

  2. Disruption of centrifugal inhibition to olfactory bulb granule cells impairs olfactory discrimination

    PubMed Central

    Nunez-Parra, Alexia; Maurer, Robert K.; Krahe, Krista; Smith, Richard S.; Araneda, Ricardo C.

    2013-01-01

    Granule cells (GCs) are the most abundant inhibitory neuronal type in the olfactory bulb and play a critical role in olfactory processing. GCs regulate the activity of principal neurons, the mitral cells, through dendrodendritic synapses, shaping the olfactory bulb output to other brain regions. GC excitability is regulated precisely by intrinsic and extrinsic inputs, and this regulation is fundamental for odor discrimination. Here, we used channelrhodopsin to stimulate GABAergic axons from the basal forebrain selectively and show that this stimulation generates reliable inhibitory responses in GCs. Furthermore, selective in vivo inhibition of GABAergic neurons in the basal forebrain by targeted expression of designer receptors exclusively activated by designer drugs produced a reversible impairment in the discrimination of structurally similar odors, indicating an important role of these inhibitory afferents in olfactory processing. PMID:23959889

  3. Centrifugal telencephalic afferent connections to the main and accessory olfactory bulbs.

    PubMed

    Mohedano-Moriano, Alicia; de la Rosa-Prieto, Carlos; Saiz-Sanchez, Daniel; Ubeda-Bañon, Isabel; Pro-Sistiaga, Palma; de Moya-Pinilla, Miguel; Martinez-Marcos, Alino

    2012-01-01

    Parallel to the olfactory system, most mammals possess an accessory olfactory or vomeronasal system. The olfactory and vomeronasal epithelia project to the main and accessory olfactory bulbs, which in turn project to adjacent areas of the telencephalon, respectively. New data indicate that projections arising from the main and accessory olfactory bulbs partially converge in the rostral telencephalon and are non-overlapping at caudal telencephalic levels. Therefore, the basal telencephalon should be reclassified in olfactory, vomeronasal, and mixed areas. On the other hand, it has been demonstrated that virtually all olfactory- and vomeronasal-recipient structures send reciprocal projections to the main and accessory olfactory bulbs, respectively. Further, non-chemosensory recipient structures also projects centrifugally to the olfactory bulbs. These feed-back projections appear to be essential modulating processing of chemosensory information. The present work aims at characterizing centrifugal projections to the main and accessory olfactory bulbs arising from olfactory, vomeronasal, mixed, and non-chemosensory recipient telencephalic areas. This issue has been addressed by using tracer injections in the rat and mouse brain. Tracer injections were delivered into the main and accessory olfactory bulbs as well as in olfactory, vomeronasal, mixed, and non-chemosensory recipient telencephalic structures. The results confirm that olfactory- and vomeronasal-recipient structures project to the main and accessory olfactory bulbs, respectively. Interestingly, olfactory (e.g., piriform cortex), vomeronasal (e.g., posteromedial cortical amygdala), mixed (e.g., the anterior medial amygdaloid nucleus), and non-chemosensory-recipient (e.g., the nucleus of the diagonal band) structures project to the main and to the accessory olfactory bulbs thus providing the possibility of simultaneous modulation and interaction of both systems at different stages of chemosensory processing.

  4. Centrifugal telencephalic afferent connections to the main and accessory olfactory bulbs

    PubMed Central

    Mohedano-Moriano, Alicia; de la Rosa-Prieto, Carlos; Saiz-Sanchez, Daniel; Ubeda-Bañon, Isabel; Pro-Sistiaga, Palma; de Moya-Pinilla, Miguel; Martinez-Marcos, Alino

    2012-01-01

    Parallel to the olfactory system, most mammals possess an accessory olfactory or vomeronasal system. The olfactory and vomeronasal epithelia project to the main and accessory olfactory bulbs, which in turn project to adjacent areas of the telencephalon, respectively. New data indicate that projections arising from the main and accessory olfactory bulbs partially converge in the rostral telencephalon and are non-overlapping at caudal telencephalic levels. Therefore, the basal telencephalon should be reclassified in olfactory, vomeronasal, and mixed areas. On the other hand, it has been demonstrated that virtually all olfactory- and vomeronasal-recipient structures send reciprocal projections to the main and accessory olfactory bulbs, respectively. Further, non-chemosensory recipient structures also projects centrifugally to the olfactory bulbs. These feed-back projections appear to be essential modulating processing of chemosensory information. The present work aims at characterizing centrifugal projections to the main and accessory olfactory bulbs arising from olfactory, vomeronasal, mixed, and non-chemosensory recipient telencephalic areas. This issue has been addressed by using tracer injections in the rat and mouse brain. Tracer injections were delivered into the main and accessory olfactory bulbs as well as in olfactory, vomeronasal, mixed, and non-chemosensory recipient telencephalic structures. The results confirm that olfactory- and vomeronasal-recipient structures project to the main and accessory olfactory bulbs, respectively. Interestingly, olfactory (e.g., piriform cortex), vomeronasal (e.g., posteromedial cortical amygdala), mixed (e.g., the anterior medial amygdaloid nucleus), and non-chemosensory-recipient (e.g., the nucleus of the diagonal band) structures project to the main and to the accessory olfactory bulbs thus providing the possibility of simultaneous modulation and interaction of both systems at different stages of chemosensory processing

  5. Increasing olfactory bulb volume due to treatment of chronic rhinosinusitis--a longitudinal study.

    PubMed

    Gudziol, V; Buschhüter, D; Abolmaali, N; Gerber, J; Rombaux, P; Hummel, T

    2009-11-01

    Differentiation of progenitor cells into neurons in the olfactory bulb depends on olfactory stimulation that can lead to an increase in olfactory bulb volume. In this study, we investigated whether the human olfactory bulb volume increases with increasing olfactory function due to treatment of chronic rhinosinusitis. Nineteen patients with chronic rhinosinusitis were investigated before and after treatment. For comparison, additional measurements were performed in 18 healthy volunteers. Volumetric measurements of the olfactory bulb were based on planimetric manual contouring of magnetic resonance scans. Olfactory function was evaluated separately for each nostril using tests for odour threshold, odour discrimination and odour identification. Measurements were performed on two occasions, 3 months apart. In healthy controls, the olfactory bulb volume did not change significantly between the two measurements. In contrast, the olfactory bulb volume in patients increased significantly from the initial 64.5 +/- 3.2 to 70.0 +/- 3.5 mm(3) on the left side (P = 0.02) and from 60.9 +/- 3.5 to 72.4 +/- 2.8 mm(3) on the right side (P < 0.001). The increase in olfactory bulb volume correlated significantly with an increase in odour thresholds (r = 0.60, P = 0.006, left side; r = 0.49, P = 0.03, right side), but not with changes in odour discrimination or odour identification. Results of this study support the idea that stimulation of olfactory receptor neurons impacts on the cell death in the olfactory bulb, not only in rodents but also in humans. To our knowledge, this is the first longitudinal study that describes an enlargement of the human olfactory bulb due to improvement of peripheral olfactory function. PMID:19773353

  6. Olfactory bulb recovery following reversible deafferentation with repeated detergent application in the adult zebrafish.

    PubMed

    Paskin, T R; Iqbal, T R; Byrd-Jacobs, C A

    2011-11-24

    The neuroplasticity and regenerative properties of the olfactory system make it a useful model for studying the ability of the nervous system to recover from damage. We have developed a novel method for examining the effects of long-term deafferentation and regeneration of the olfactory organ and resulting influence on the olfactory bulb in adult zebrafish. To test the hypothesis that repeated damage to the olfactory epithelium causes reduced olfactory bulb afferent input and cessation of treatment allows recovery, we chronically ablated the olfactory organ every 2-3 days for 3 weeks with the detergent Triton X-100 while another group was allowed 3 weeks of recovery following treatment. Animals receiving chronic treatment showed severe morphological disruption of the olfactory organ, although small pockets of epithelium remained. These pockets were labeled by anti-calretinin, indicating the presence of mature olfactory sensory neurons (OSNs). Following a recovery period, the epithelium was more extensive and neuronal labeling increased, with three different morphologies of sensory neurons observed. Repeated peripheral exposure to Triton X-100 also affected the olfactory bulb. Bulb volumes and anti-tyrosine hydroxylase-like immunoreactivity, which is an indicator of afferent activity, were diminished in the olfactory bulb of the chronically treated group compared to the control side. In the recovery group, there was little difference in bulb volume or antibody staining. These results suggest that repeated, long-term nasal irrigation with Triton X-100 eliminates a substantial number of mature OSNs and reduces afferent input to the olfactory bulb. It also appears that these effects are reversible and regeneration will occur in both the peripheral olfactory organ and the olfactory bulb when given time to recover following cessation of treatment. We report here a new method that allows observation not only of the effects of deafferentation on the olfactory bulb but also

  7. Response Patterns of Single Neurons in the Tortoise Olfactory Epithelium and Olfactory Bulb

    PubMed Central

    Mathews, Donald F.

    1972-01-01

    The responses to odor stimulation of 40 single units in the olfactory mucosa and of 18 units in the olfactory bulb of the tortoise (Gopherus polyphemus) were recorded with indium-filled, Pt-black-tipped microelectrodes. The test battery consisted of 27 odorants which were proved effective by recording from small bundles of olfactory nerve. Two concentrations of each odorant were employed. These values were adjusted for response magnitudes equal to those for amyl acetate at –2.5 and –3.5 log concentration in olfactory twig recording. Varying concentrations were generated by an injection-type olfactometer. The mucosal responses were exclusively facilitory with a peak frequency of 16 impulses/sec. 19 mucosal units responded to at least one odorant and each unit was sensitive to a limited number of odorants (1–15). The sensitivity pattern of each unit was highly individual, with no clear-cut types, either chemical or qualitative, emerging. Of the 18 olfactory bulb units sampled, all responded to at least one odorant. The maximum frequency observed during a response was 39 impulses/sec. The bulbar neurons can be classified into two types. There are neurons that respond exclusively with facilitation and others that respond with facilitation to some odorants and with inhibition to others. Qualitatively or chemically similar odorants did not generate similar patterns across bulbar units. PMID:5049077

  8. Photoperiod mediated changes in olfactory bulb neurogenesis and olfactory behavior in male white-footed mice (Peromyscus leucopus).

    PubMed

    Walton, James C; Pyter, Leah M; Weil, Zachary M; Nelson, Randy J

    2012-01-01

    Brain plasticity, in relation to new adult mammalian neurons generated in the subgranular zone of the hippocampus, has been well described. However, the functional outcome of new adult olfactory neurons born in the subventricular zone of the lateral ventricles is not clearly defined, as manipulating neurogenesis through various methods has given inconsistent and conflicting results in lab mice. Several small rodent species, including Peromyscus leucopus, display seasonal (photoperiodic) brain plasticity in brain volume, hippocampal function, and hippocampus-dependent behaviors; plasticity in the olfactory system of photoperiodic rodents remains largely uninvestigated. We exposed adult male P. leucopus to long day lengths (LD) and short day lengths (SD) for 10 to 15 weeks and then examined olfactory bulb cell proliferation and survival using the thymidine analog BrdU, olfactory bulb granule cell morphology using Golgi-Cox staining, and behavioral investigation of same-sex conspecific urine. SD mice did not differ from LD counterparts in granular cell morphology of the dendrites or in dendritic spine density. Although there were no differences due to photoperiod in habituation to water odor, SD mice rapidly habituated to male urine, whereas LD mice did not. In addition, short day induced changes in olfactory behavior were associated with increased neurogenesis in the caudal plexiform and granule cell layers of the olfactory bulb, an area known to preferentially respond to water-soluble odorants. Taken together, these data demonstrate that photoperiod, without altering olfactory bulb neuronal morphology, alters olfactory bulb neurogenesis and olfactory behavior in Peromyscus leucopus. PMID:22912730

  9. Photoperiod mediated changes in olfactory bulb neurogenesis and olfactory behavior in male white-footed mice (Peromyscus leucopus).

    PubMed

    Walton, James C; Pyter, Leah M; Weil, Zachary M; Nelson, Randy J

    2012-01-01

    Brain plasticity, in relation to new adult mammalian neurons generated in the subgranular zone of the hippocampus, has been well described. However, the functional outcome of new adult olfactory neurons born in the subventricular zone of the lateral ventricles is not clearly defined, as manipulating neurogenesis through various methods has given inconsistent and conflicting results in lab mice. Several small rodent species, including Peromyscus leucopus, display seasonal (photoperiodic) brain plasticity in brain volume, hippocampal function, and hippocampus-dependent behaviors; plasticity in the olfactory system of photoperiodic rodents remains largely uninvestigated. We exposed adult male P. leucopus to long day lengths (LD) and short day lengths (SD) for 10 to 15 weeks and then examined olfactory bulb cell proliferation and survival using the thymidine analog BrdU, olfactory bulb granule cell morphology using Golgi-Cox staining, and behavioral investigation of same-sex conspecific urine. SD mice did not differ from LD counterparts in granular cell morphology of the dendrites or in dendritic spine density. Although there were no differences due to photoperiod in habituation to water odor, SD mice rapidly habituated to male urine, whereas LD mice did not. In addition, short day induced changes in olfactory behavior were associated with increased neurogenesis in the caudal plexiform and granule cell layers of the olfactory bulb, an area known to preferentially respond to water-soluble odorants. Taken together, these data demonstrate that photoperiod, without altering olfactory bulb neuronal morphology, alters olfactory bulb neurogenesis and olfactory behavior in Peromyscus leucopus.

  10. Photoperiod Mediated Changes in Olfactory Bulb Neurogenesis and Olfactory Behavior in Male White-Footed Mice (Peromyscus leucopus)

    PubMed Central

    Weil, Zachary M.; Nelson, Randy J.

    2012-01-01

    Brain plasticity, in relation to new adult mammalian neurons generated in the subgranular zone of the hippocampus, has been well described. However, the functional outcome of new adult olfactory neurons born in the subventricular zone of the lateral ventricles is not clearly defined, as manipulating neurogenesis through various methods has given inconsistent and conflicting results in lab mice. Several small rodent species, including Peromyscus leucopus, display seasonal (photoperiodic) brain plasticity in brain volume, hippocampal function, and hippocampus-dependent behaviors; plasticity in the olfactory system of photoperiodic rodents remains largely uninvestigated. We exposed adult male P. leucopus to long day lengths (LD) and short day lengths (SD) for 10 to 15 weeks and then examined olfactory bulb cell proliferation and survival using the thymidine analog BrdU, olfactory bulb granule cell morphology using Golgi-Cox staining, and behavioral investigation of same-sex conspecific urine. SD mice did not differ from LD counterparts in granular cell morphology of the dendrites or in dendritic spine density. Although there were no differences due to photoperiod in habituation to water odor, SD mice rapidly habituated to male urine, whereas LD mice did not. In addition, short day induced changes in olfactory behavior were associated with increased neurogenesis in the caudal plexiform and granule cell layers of the olfactory bulb, an area known to preferentially respond to water-soluble odorants. Taken together, these data demonstrate that photoperiod, without altering olfactory bulb neuronal morphology, alters olfactory bulb neurogenesis and olfactory behavior in Peromyscus leucopus. PMID:22912730

  11. Adult neurogenesis restores dopaminergic neuronal loss in the olfactory bulb.

    PubMed

    Lazarini, Françoise; Gabellec, Marie-Madeleine; Moigneu, Carine; de Chaumont, Fabrice; Olivo-Marin, Jean-Christophe; Lledo, Pierre-Marie

    2014-10-22

    Subventricular zone (SVZ) neurogenesis continuously provides new GABA- and dopamine (DA)-containing interneurons for the olfactory bulb (OB) in most adult mammals. DAergic interneurons are located in the glomerular layer (GL) where they participate in the processing of sensory inputs. To examine whether adult neurogenesis might contribute to regeneration after circuit injury in mice, we induce DAergic neuronal loss by injecting 6-hydroxydopamine (6-OHDA) in the dorsal GL or in the right substantia nigra pars compacta. We found that a 6-OHDA treatment of the OB produces olfactory deficits and local inflammation and partially decreases the number of neurons expressing the enzyme tyrosine hydroxylase (TH) near the injected site. Blockade of inflammation by minocycline treatment immediately after the 6-OHDA administration rescued neither TH(+) interneuron number nor the olfactory deficits, suggesting that the olfactory impairments are most likely linked to TH(+) cell death and not to microglial activation. TH(+) interneuron number was restored 1 month later. This rescue resulted at least in part from enhanced recruitment of immature neurons targeting the lesioned GL area. Seven days after 6-OHDA lesion in the OB, we found that the integration of lentivirus-labeled adult-born neurons was biased: newly formed neurons were preferentially incorporated into glomerular circuits of the lesioned area. Behavioral rehabilitation occurs 2 months after lesion. This study establishes a new model into which loss of DAergic cells could be compensated by recruiting newly formed neurons. We propose that adult neurogenesis not only replenishes the population of DAergic bulbar neurons but that it also restores olfactory sensory processing. PMID:25339754

  12. Functional properties of dopaminergic neurones in the mouse olfactory bulb

    PubMed Central

    Pignatelli, Angela; Kobayashi, Kazuto; Okano, Hideyuki; Belluzzi, Ottorino

    2005-01-01

    The olfactory bulb of mammals contains a large population of dopaminergic interneurones within the glomerular layer. Dopamine has been shown both in vivo and in vitro to modulate several aspects of olfactory information processing, but the functional properties of dopaminergic neurones have never been described due to the inability to recognize these cells in living preparations. To overcome this difficulty, we used a transgenic mouse strain harbouring an eGFP (enhanced green fluorescent protein) reporter construct under the promoter of tyrosine hydroxylase, the rate-limiting enzyme for cathecolamine synthesis. As a result, we were able to identify dopaminergic neurones (TH-GFP cells) in living preparations and, for the first time, we could study the functional properties of such neurones in the olfactory bulb, in both slices and dissociated cells. The most prominent feature of these cells was the autorhythmicity. In these cells we identified five main voltage-dependent conductances: the two having largest amplitude were a fast transient Na+ current and a delayed rectifier K+ current. In addition, we observed three smaller inward currents, sustained by Na+ ions (persistent type) and by Ca2+ ions (LVA and HVA). Using pharmacological tools and ion substitution methods we showed that the pacemaking process is supported by the interplay of the persistent Na+ current and of a T-type Ca2+ current. We carried out a complete kinetical analysis of the five conductances present in these cells, and developed a Hodgkin-Huxley model of TH-GFP cells, capable of reproducing accurately the properties of living cells, including autorhytmicity, and allowing a precise understanding of the process. PMID:15731185

  13. Involvement of TRPV1 in the Olfactory Bulb in Rimonabant-Induced Olfactory Discrimination Deficit.

    PubMed

    Hu, Sherry Shu-Jung

    2016-02-29

    Rimonabant is well recognized as a cannabinoid CB₁ receptor antagonist/inverse agonist. Rimonabant not only antagonizes the effects induced by exogenous cannabinoids and endocannabinoids at CB₁ receptors, it also exerts several pharmacological and behavioral effects independent of CB₁ receptor inactivation. For example, rimonabant can function as a low-potency mixed agonist/antagonist of the transient receptor potential vanilloid receptor 1 (TRPV1). Hence, it is important to explain the underlying mechanisms of the diverse physiological effects induced by rimonabant with caution. Interestingly, CB₁ receptor has recently been suggested to play a role in olfactory functions. Olfaction not only is involved in food intake, visual perception and social interaction, but also is proposed as a putative marker for schizophrenia and autism. Therefore, the present study aimed to investigate whether CB₁ receptor and TRPV1 played a role in olfactory functions. We first used the genetic disruption approach to examine the role of CB₁ receptor in olfactory functions and found that CB₁ knockout mice exhibited olfactory discrimination deficit. However, it is important to point out that these CB₁ knockout mice, despite their normal locomotivity, displayed deficiencies in the olfactory foraging and novel object exploration tasks. These results imply that general exploratory behaviors toward odorant and odorless objects are compromised in CB₁ knockout mice. We next turned to the pharmacological approach to examine the role of CB₁ receptor and TRPV1 in olfactory functions. We found that the short-term administration of rimonabant, injected systemically or directly into the olfactory bulb (OB), impaired olfactory discrimination that was rescued by the TRPV1 antagonist capsazepine (CPZ), via the same route of rimonabant, in wild-type mice. These results suggest that TRPV1 in the OB is involved in rimonabant-induced olfactory discrimination deficit. However, the

  14. The olfactory bulb structure of African giant rat (Cricetomys gambianus, Waterhouse 1840) I: cytoarchitecture.

    PubMed

    Olude, M A; Ogunbunmi, T K; Olopade, J O; Ihunwo, A O

    2014-09-01

    The olfactory system typically consists of two parallel systems: the main olfactory system and the accessory olfactory system. The main olfactory bulb (MOB) acts as the initial processing site for volatile chemical stimuli and receives input from the olfactory receptor cells located in the olfactory epithelium. The African giant rat is reputed to have abilities to detect landmines and tuberculosis samples by sniffing. This study therefore is a preliminary study on the histological and immunohistochemical anatomy of the olfactory bulb of the African giant rat (Cricetomys gambianus, Waterhouse). Nissl and Klüver-Barrera histological staining of the olfactory bulb revealed a cytoarchitecture typical of most mammals with 6 cell layers, and 1-2-layered glomeruli measuring approximately 150 μm each in diameter. Immunohistochemical staining with glial fibrillary acidic protein (GFAP) and 2',3'-cyclic nucleotide 3-phosphodiesterase (CNPase) revealed cellular conformations relative to most mammals. GFAP immunohistochemistry also revealed cell bodies and processes within the periglomerular area which may potentiate signaling from the olfactory receptor cells, while CNPase largely showed soma and evidence of myelin sheath deposition, confirming myelination at different layers of the bulb. Neurogenesis was examined using the neurogenic markers doublecortin (DCX) and Ki-67. Migration of newly generated cells was observed in all layers of the MOB with DCX and in most layers with Ki-67. The anatomy of the olfactory bulb is described as relatively large in the African giant rat, having a neuroarchitecture similar to most rodents.

  15. Structure and diversity in mammalian accessory olfactory bulb.

    PubMed

    Meisami, E; Bhatnagar, K P

    1998-12-15

    The accessory olfactory bulb (AOB) is the first neural integrative center for the olfactory-like vomeronasal sensory system. In this article, we first briefly present an overview of vomeronasal system organization and review the history of the discovery of mammalian AOB. Next, we briefly review the evolution of the vomeronasal system in vertebrates, in particular the reptiles. Following these introductory aspects, the structure of the rodent AOB, as typical of the well-developed mammalian AOB, is presented, detailing laminar organization and cell types as well as aspects of the homology with the main olfactory bulb. Then, the evolutionary origin and diversity of the AOB in mammalian orders and species is discussed, describing structural, phylogenetic, and species-specific variation in the AOB location, shape, and size and morphologic differentiation and development. The AOB is believed to be absent in fishes but present in terrestrial tetrapods including amphibians; among the reptiles AOB is absent in crocodiles, present in turtles, snakes, and some lizards where it may be as large or larger than the main bulb. The AOB is absent in bird and in the aquatic mammals (whales, porpoises, manatees). Among other mammals, AOB is present in the monotremes and marsupials, edentates, and in the majority of the placental mammals like carnivores, herbivores, as well as rodents and lagomorphs. Most bat species do not have an AOB and among those where one is found, it shows marked variation in size and morphologic development. Among insectivores and primates, AOB shows marked variation in occurrence, size, and morphologic development. It is small in shrews and moles, large in hedgehogs and prosimians; AOB continues to persist in New World monkeys but is not found in the adults of the higher primates such as the Old World monkeys, apes, and humans. In many species where AOB is absent in the adult, it often develops in the embryo and fetus but regresses in later stages of

  16. Local postsynaptic voltage-gated sodium channel activation in dendritic spines of olfactory bulb granule cells.

    PubMed

    Bywalez, Wolfgang G; Patirniche, Dinu; Rupprecht, Vanessa; Stemmler, Martin; Herz, Andreas V M; Pálfi, Dénes; Rózsa, Balázs; Egger, Veronica

    2015-02-01

    Neuronal dendritic spines have been speculated to function as independent computational units, yet evidence for active electrical computation in spines is scarce. Here we show that strictly local voltage-gated sodium channel (Nav) activation can occur during excitatory postsynaptic potentials in the spines of olfactory bulb granule cells, which we mimic and detect via combined two-photon uncaging of glutamate and calcium imaging in conjunction with whole-cell recordings. We find that local Nav activation boosts calcium entry into spines through high-voltage-activated calcium channels and accelerates postsynaptic somatic depolarization, without affecting NMDA receptor-mediated signaling. Hence, Nav-mediated boosting promotes rapid output from the reciprocal granule cell spine onto the lateral mitral cell dendrite and thus can speed up recurrent inhibition. This striking example of electrical compartmentalization both adds to the understanding of olfactory network processing and broadens the general view of spine function.

  17. Neuronal fate determinants of adult olfactory bulb neurogenesis.

    PubMed

    Hack, Michael A; Saghatelyan, Armen; de Chevigny, Antoine; Pfeifer, Alexander; Ashery-Padan, Ruth; Lledo, Pierre-Marie; Götz, Magdalena

    2005-07-01

    Adult neurogenesis in mammals is restricted to two small regions, including the olfactory bulb, where GABAergic and dopaminergic interneurons are newly generated throughout the entire lifespan. However, the mechanisms directing them towards a specific neuronal phenotype are not yet understood. Here, we demonstrate the dual role of the transcription factor Pax6 in generating neuronal progenitors and also in directing them towards a dopaminergic periglomerular phenotype in adult mice. We present further evidence that dopaminergic periglomerular neurons originate in a distinct niche, the rostral migratory stream, and are fewer derived from precursors in the zone lining the ventricle. This regionalization of the adult precursor cells is further supported by the restricted expression of the transcription factor Olig2, which specifies transit-amplifying precursor fate and opposes the neurogenic role of Pax6. Together, these data explain both extrinsic and intrinsic mechanisms controlling neuronal identity in adult neurogenesis.

  18. Subicular and CA1 hippocampal projections to the accessory olfactory bulb.

    PubMed

    de la Rosa-Prieto, C; Ubeda-Banon, I; Mohedano-Moriano, A; Pro-Sistiaga, P; Saiz-Sanchez, D; Insausti, R; Martinez-Marcos, A

    2009-02-01

    The hippocampal formation is anatomically and functionally related to the olfactory structures especially in rodents. The entorhinal cortex (EC) receives afferent projections from the main olfactory bulb; this constitutes an olfactory pathway to the hippocampus. In addition to the olfactory system, most mammals possess an accessory olfactory (or vomeronasal) system. The relationships between the hippocampal formation and the vomeronasal system are virtually unexplored. Recently, a centrifugal projection from CA1 to the accessory olfactory bulb has been identified using anterograde tracers. In the study reported herein, experiments using anterograde tracers confirm this projection, and injections of retrograde tracers show the distribution and morphology of a population of CA1 and ventral subicular neurons projecting to the accessory olfactory bulb of rats. These results extend previous descriptions of hippocampal projections to the accessory olfactory bulb by including the ventral subiculum and characterizing the morphology, neurochemistry (double labeling with somatostatin), and distribution of such neurons. These data suggest feedback hippocampal control of chemosensory stimuli in the accessory olfactory bulb. Whether this projection processes spatial information on conspecifics or is involved in learning and memory processes associated with chemical stimuli remains to be elucidated.

  19. Rauwolfia vomitoria inhibits olfaction and modifies olfactory bulb cells.

    PubMed

    Ekong, Moses B; Peter, Aniekan I; Edagha, Innocent A; Ekpene, Ubong U; Friday, Daniel A

    2016-06-01

    The rising cost of orthodox medication has endeared so many to the use of herbs for the management of neurological conditions. Rauwolfia vomitoria (RV) one of such herbs is a rainforest shrub whose parts are used locally in the management of psychiatry and other medical issues. Its usefulness though not in doubt is wrapped with adverse reports as its active constituents depletes brain monoamine and dopamine stores. This motivated this research on the effects of the root bark extract on olfaction and the olfactory bulb of adult Wistar rats. Eighteen adult Wistar rats (220g average) were divided into three groups (n=6); control (placebo), 200mg/kg and 400mg/kg RV root bark extract, respectively. The oral administration lasted for seven days and on day 8, test of olfaction was carried out and the animals immediately anaesthetized with ketamine hydrochloride (i.p.) and perfuse-fixed with 10% neutral buffered formalin. All the brains were processed for histology and immunoreactivity. Results showed loss of body weights and olfaction in the 200mg/kg and 400mg/kg RV groups. There was hypertrophy and atrophy of mitral cells respectively, in the 200mg/kg and 400mg/kg RV groups, while there was hyperplasia of cells in the internal granular and plexiform layers of both groups. There was decreased neuron specific enolase (NSE) and neurofilament (NF) expression in the 200mg/kg RV group, while NF and glial fibrillary acidic protein (GFAP) expression was decreased in the 400mg/kg RV group. However, NSE expression was enhanced in the 400mg/kg group, while GFAP expression was enhanced in the 200mg/kg RV group. These results suggest that these doses of RV affect olfaction and appetite, and stimulate adverse cellular changes in the olfactory bulb.

  20. Rauwolfia vomitoria inhibits olfaction and modifies olfactory bulb cells.

    PubMed

    Ekong, Moses B; Peter, Aniekan I; Edagha, Innocent A; Ekpene, Ubong U; Friday, Daniel A

    2016-06-01

    The rising cost of orthodox medication has endeared so many to the use of herbs for the management of neurological conditions. Rauwolfia vomitoria (RV) one of such herbs is a rainforest shrub whose parts are used locally in the management of psychiatry and other medical issues. Its usefulness though not in doubt is wrapped with adverse reports as its active constituents depletes brain monoamine and dopamine stores. This motivated this research on the effects of the root bark extract on olfaction and the olfactory bulb of adult Wistar rats. Eighteen adult Wistar rats (220g average) were divided into three groups (n=6); control (placebo), 200mg/kg and 400mg/kg RV root bark extract, respectively. The oral administration lasted for seven days and on day 8, test of olfaction was carried out and the animals immediately anaesthetized with ketamine hydrochloride (i.p.) and perfuse-fixed with 10% neutral buffered formalin. All the brains were processed for histology and immunoreactivity. Results showed loss of body weights and olfaction in the 200mg/kg and 400mg/kg RV groups. There was hypertrophy and atrophy of mitral cells respectively, in the 200mg/kg and 400mg/kg RV groups, while there was hyperplasia of cells in the internal granular and plexiform layers of both groups. There was decreased neuron specific enolase (NSE) and neurofilament (NF) expression in the 200mg/kg RV group, while NF and glial fibrillary acidic protein (GFAP) expression was decreased in the 400mg/kg RV group. However, NSE expression was enhanced in the 400mg/kg group, while GFAP expression was enhanced in the 200mg/kg RV group. These results suggest that these doses of RV affect olfaction and appetite, and stimulate adverse cellular changes in the olfactory bulb. PMID:27208729

  1. Map Formation in the Olfactory Bulb by Axon Guidance of Olfactory Neurons

    PubMed Central

    Auffarth, Benjamin; Kaplan, Bernhard; Lansner, Anders

    2011-01-01

    The organization of representations in the brain has been observed to locally reflect subspaces of inputs that are relevant to behavioral or perceptual feature combinations, such as in areas receptive to lower and higher-order features in the visual system. The early olfactory system developed highly plastic mechanisms and convergent evidence indicates that projections from primary neurons converge onto the glomerular level of the olfactory bulb (OB) to form a code composed of continuous spatial zones that are differentially active for particular physico-chemical feature combinations, some of which are known to trigger behavioral responses. In a model study of the early human olfactory system, we derive a glomerular organization based on a set of real-world, biologically relevant stimuli, a distribution of receptors that respond each to a set of odorants of similar ranges of molecular properties, and a mechanism of axon guidance based on activity. Apart from demonstrating activity-dependent glomeruli formation and reproducing the relationship of glomerular recruitment with concentration, it is shown that glomerular responses reflect similarities of human odor category perceptions and that further, a spatial code provides a better correlation than a distributed population code. These results are consistent with evidence of functional compartmentalization in the OB and could suggest a function for the bulb in encoding of perceptual dimensions. PMID:22013417

  2. Organization of the main olfactory bulb of lesser hedgehog tenrecs.

    PubMed

    Kosaka, Katsuko; Künzle, Heinz; Kosaka, Toshio

    2005-12-01

    Using a confocal laser scanning microscope (CLSM) and an electron microscope, we investigated the organization of the main olfactory bulb (MOB) of tenrecs, which were previously included into insectivores but now considered to be in a new order "Afrosoricida" in the superclade 'Afrotheria'. We confirmed that the overall structural organization of the tenrec MOB was similar to that of rodents: (1) the compartmental organization of glomeruli and two types of periglomerular cells we proposed as the common organizational principles were present; (2) there were characteristic dendrodendritic and axo-dendritic synapses in the glomerulus and external plexiform layer (EPL) and gap junctions in glomeruli; and (3) no nidi, particular synaptic regions reported only in laboratory musk shrew and mole MOBs, were encountered. However, instead of nidi, we often observed a few tangled olfactory nerves (ONs) with large irregular boutons in the glomerular-external plexiform layer border zone, with which dendrites of various displaced periglomerular cells were usually found to be intermingled. Electron microscopic (EM) examinations confirmed characteristic large mossy terminal-like ON terminals making asymmetrical synapses to presumed mitral/tufted cell and displaced periglomerular cell dendrites. In addition, gap junctions were also encountered between dendritic processes in these tiny particular regions, further showing their resemblance to glomeruli.

  3. Functional transformations of odor inputs in the mouse olfactory bulb.

    PubMed

    Adam, Yoav; Livneh, Yoav; Miyamichi, Kazunari; Groysman, Maya; Luo, Liqun; Mizrahi, Adi

    2014-01-01

    Sensory inputs from the nasal epithelium to the olfactory bulb (OB) are organized as a discrete map in the glomerular layer (GL). This map is then modulated by distinct types of local neurons and transmitted to higher brain areas via mitral and tufted cells. Little is known about the functional organization of the circuits downstream of glomeruli. We used in vivo two-photon calcium imaging for large scale functional mapping of distinct neuronal populations in the mouse OB, at single cell resolution. Specifically, we imaged odor responses of mitral cells (MCs), tufted cells (TCs) and glomerular interneurons (GL-INs). Mitral cells population activity was heterogeneous and only mildly correlated with the olfactory receptor neuron (ORN) inputs, supporting the view that discrete input maps undergo significant transformations at the output level of the OB. In contrast, population activity profiles of TCs were dense, and highly correlated with the odor inputs in both space and time. Glomerular interneurons were also highly correlated with the ORN inputs, but showed higher activation thresholds suggesting that these neurons are driven by strongly activated glomeruli. Temporally, upon persistent odor exposure, TCs quickly adapted. In contrast, both MCs and GL-INs showed diverse temporal response patterns, suggesting that GL-INs could contribute to the transformations MCs undergo at slow time scales. Our data suggest that sensory odor maps are transformed by TCs and MCs in different ways forming two distinct and parallel information streams.

  4. Massive normalization of olfactory bulb output in mice with a 'monoclonal nose'

    PubMed Central

    Roland, Benjamin; Jordan, Rebecca; Sosulski, Dara L; Diodato, Assunta; Fukunaga, Izumi; Wickersham, Ian; Franks, Kevin M; Schaefer, Andreas T; Fleischmann, Alexander

    2016-01-01

    Perturbations in neural circuits can provide mechanistic understanding of the neural correlates of behavior. In M71 transgenic mice with a “monoclonal nose”, glomerular input patterns in the olfactory bulb are massively perturbed and olfactory behaviors are altered. To gain insights into how olfactory circuits can process such degraded inputs we characterized odor-evoked responses of olfactory bulb mitral cells and interneurons. Surprisingly, calcium imaging experiments reveal that mitral cell responses in M71 transgenic mice are largely normal, highlighting a remarkable capacity of olfactory circuits to normalize sensory input. In vivo whole cell recordings suggest that feedforward inhibition from olfactory bulb periglomerular cells can mediate this signal normalization. Together, our results identify inhibitory circuits in the olfactory bulb as a mechanistic basis for many of the behavioral phenotypes of mice with a “monoclonal nose” and highlight how substantially degraded odor input can be transformed to yield meaningful olfactory bulb output. DOI: http://dx.doi.org/10.7554/eLife.16335.001 PMID:27177421

  5. Expression of polysialyltransferases (STX and PST) in adult rat olfactory bulb after an olfactory associative discrimination task.

    PubMed

    Mione, J; Manrique, C; Duhoo, Y; Roman, F S; Guiraudie-Capraz, G

    2016-04-01

    Neuronal plasticity and neurogenesis occur in the adult hippocampus and in other brain structures such as the olfactory bulb and often involve the neural cell adhesion molecule NCAM. During an olfactory associative discrimination learning task, NCAM polysialylation triggers neuronal plasticity in the adult hippocampus. The PST enzyme likely modulates this polysialylation, but not STX, a second sialyltransferase. How the two polysialyltransferases are involved in the adult olfactory bulb remains unknown. We addressed this question by investigating the effect of olfactory associative learning on plasticity and neurogenesis. After a hippocampo-dependent olfactory associative task learning, we measured the expression of both PST and STX polysialyltransferases in the olfactory bulbs of adult rats using quantitative PCR. In parallel, immunohistochemistry was used to evaluate both NCAM polysialylation level and newly-born cells, with or without learning. After learning, no changes were observed neither in the expression level of PST and NCAM polysialylation, nor in STX gene expression level and newly-born cells number in the olfactory bulb.

  6. Formaldehyde exposure alters miRNA expression profiles in the olfactory bulb.

    PubMed

    Li, Guifa; Yang, Jing; Ling, Shucai

    2015-01-01

    It has been reported that inhaling formaldehyde (FA) causes damage to the central nervous system. However, it is unclear whether FA can disturb the function of the olfactory bulb. Using a microarray, we found that FA inhalation altered the miRNA expression profile. Functional enrichment analysis of the predicted targets of the changed miRNA showed that the enrichment canonical pathways and networks associated with cancer and transcriptional regulation. FA exposure disrupts miRNA expression profiles within the olfactory bulb.

  7. The olfactory conditioning in the early postnatal period stimulated neural stem/progenitor cells in the subventricular zone and increased neurogenesis in the olfactory bulb of rats.

    PubMed

    So, K; Moriya, T; Nishitani, S; Takahashi, H; Shinohara, K

    2008-01-01

    The olfactory memory acquired during the early postnatal period is known to be maintained for a long period, however, its neural mechanism remains to be clarified. In the present study, we examined the effect of olfactory conditioning during the early postnatal period on neurogenesis in the olfactory bulb of rats. Using the bromodeoxyuridine-pulse chase method, we found that the olfactory conditioning, which was a paired presentation of citral odor (conditioned stimulus) and foot shock (unconditioned stimulus) in rat pups on postnatal day 11, stimulated the proliferation of neural stem/progenitor cells in the anterior subventricular zone (aSVZ), but not in the olfactory bulb, at 24 h after the conditioning. However, the number of newborn cells in the olfactory bulb was increased at 2 weeks, but not 8 weeks, after such conditioning. Neither the exposure of a citral odor alone nor foot shock alone affected the proliferation of neural stem/progenitor cells in the aSVZ at 24 h after and the number of newborn cells in the olfactory bulb at 2 weeks after. The majority of newborn cells in the olfactory bulb of either the conditioned rats or the unconditioned rats expressed the neural marker NeuN, thus indicating that the olfactory conditioning stimulated neurogenesis in the olfactory bulb. These results suggest that olfactory conditioning during the early postnatal period temporally stimulates neurogenesis in the olfactory bulb of rats.

  8. An arterially perfused nose-olfactory bulb preparation of the rat

    PubMed Central

    Stanić, Davor; Farmer, David; Dutschmann, Mathias; Egger, Veronica

    2015-01-01

    A main feature of the mammalian olfactory bulb network is the presence of various rhythmic activities, in particular, gamma, beta, and theta oscillations, with the latter coupled to the respiratory rhythm. Interactions between those oscillations as well as the spatial distribution of network activation are likely to determine olfactory coding. Here, we describe a novel semi-intact perfused nose-olfactory bulb-brain stem preparation in rats with both a preserved olfactory epithelium and brain stem, which could be particularly suitable for the study of oscillatory activity and spatial odor mapping within the olfactory bulb, in particular, in hitherto inaccessible locations. In the perfused olfactory bulb, we observed robust spontaneous oscillations, mostly in the theta range. Odor application resulted in an increase in oscillatory power in higher frequency ranges, stimulus-locked local field potentials, and excitation or inhibition of individual bulbar neurons, similar to odor responses reported from in vivo recordings. Thus our method constitutes the first viable in situ preparation of a mammalian system that uses airborne odor stimuli and preserves these characteristic features of odor processing. This preparation will allow the use of highly invasive experimental procedures and the application of techniques such as patch-clamp recording, high-resolution imaging, and optogenetics within the entire olfactory bulb. PMID:26108959

  9. An arterially perfused nose-olfactory bulb preparation of the rat.

    PubMed

    Pérez de los Cobos Pallarés, Fernando; Stanić, Davor; Farmer, David; Dutschmann, Mathias; Egger, Veronica

    2015-09-01

    A main feature of the mammalian olfactory bulb network is the presence of various rhythmic activities, in particular, gamma, beta, and theta oscillations, with the latter coupled to the respiratory rhythm. Interactions between those oscillations as well as the spatial distribution of network activation are likely to determine olfactory coding. Here, we describe a novel semi-intact perfused nose-olfactory bulb-brain stem preparation in rats with both a preserved olfactory epithelium and brain stem, which could be particularly suitable for the study of oscillatory activity and spatial odor mapping within the olfactory bulb, in particular, in hitherto inaccessible locations. In the perfused olfactory bulb, we observed robust spontaneous oscillations, mostly in the theta range. Odor application resulted in an increase in oscillatory power in higher frequency ranges, stimulus-locked local field potentials, and excitation or inhibition of individual bulbar neurons, similar to odor responses reported from in vivo recordings. Thus our method constitutes the first viable in situ preparation of a mammalian system that uses airborne odor stimuli and preserves these characteristic features of odor processing. This preparation will allow the use of highly invasive experimental procedures and the application of techniques such as patch-clamp recording, high-resolution imaging, and optogenetics within the entire olfactory bulb.

  10. Rapid odor perception in rat olfactory bulb by microelectrode array.

    PubMed

    Zhou, Jun; Dong, Qi; Zhuang, Liu-jing; Li, Rong; Wang, Ping

    2012-12-01

    Responses of 302 mitral/tufted (M/T) cells in the olfactory bulb were recorded from 42 anesthetized freely breathing rats using a 16-channel microwire electrode array. Saturated vapors of four pure chemicals, anisole, carvone, citral and isoamyl acetate were applied. After aligning spike trains to the initial phase of the inhalation after odor onset, the responses of M/T cells showed transient temporal features including excitatory and inhibitory patterns. Both odor-evoked patterns indicated that mammals recognize odors within a short respiration cycle after odor stimulus. Due to the small amount of information received from a single cell, we pooled results from all responsive M/T cells to study the ensemble activity. The firing rates of the cell ensembles were computed over 100 ms bins and population vectors were constructed. The high dimension vectors were condensed into three dimensions for visualization using principal component analysis. The trajectories of both excitatory and inhibitory cell ensembles displayed strong dynamics during odor stimulation. The distances among cluster centers were enlarged compared to those of the resting state. Thus, we presumed that pictures of odor information sent to higher brain regions were depicted and odor discrimination was completed within the first breathing cycle. PMID:23225857

  11. Electrical properties of periglomerular cells in the frog olfactory bulb.

    PubMed

    Magherini, P C; Bardoni, R; Belluzzi, O

    1997-03-01

    Whole-cell patch clamp recording techniques were applied to periglomerular (PG) cells in slices of the frog olfactory bulb (OB) preparation to study the basic electrical properties of these inhibitory interneurons. The cells were intracellularly stained with Lucifer Yellow for precise identification. Under current-clamp conditions PG cells showed rich spontaneous excitatory synaptic activity at rest, usually leading to overshooting, TTX-sensitive action potentials. The passive cable properties of the cell membrane have been carefully characterised. Depolarisation of this neurone under voltage-clamp conditions activated a complex pattern of current flow, that has been dissected into its main components. The currents have been isolated resorting to their different kinetic and pharmacological properties. Four main voltage dependent ionic currents have been isolated, two inward currents, I(Na) and I(Ca), and two outward currents carried by potassium ions, one fast transient, I(A)-type and another similar to the delayed rectifier type. These currents have been characterised kinetically and pharmacologically. The functional implications of their properties are discussed.

  12. Learning Mechanism for Column Formation in the Olfactory Bulb

    PubMed Central

    Migliore, M.; Inzirillo, Carlo; Shepherd, Gordon M.

    2007-01-01

    Sensory discrimination requires distributed arrays of processing units. In the olfactory bulb, the processing units for odor discrimination are believed to involve dendrodendritic synaptic interactions between mitral and granule cells. There is increasing anatomical evidence that these cells are organized in columns, and that the columns processing a given odor are arranged in widely distributed arrays. Experimental evidence is lacking on the underlying learning mechanisms for how these columns and arrays are formed. To gain insight into these mechanisms, we have used a simplified realistic circuit model to test the hypothesis that distributed connectivity can self-organize through an activity-dependent dendrodendritic synaptic mechanism. The results point to action potentials propagating in the mitral cell lateral dendrites as playing a critical role in this mechanism. The model predicts that columns emerge from the interaction between the local temporal dynamics of the action potentials and the synapses that they activate during dendritic propagation. The results suggest a novel and robust learning mechanism for the development of distributed processing units in a cortical structure. PMID:18958240

  13. Olfactory Sensory Activity Modulates Microglial-Neuronal Interactions during Dopaminergic Cell Loss in the Olfactory Bulb

    PubMed Central

    Grier, Bryce D.; Belluscio, Leonardo; Cheetham, Claire E. J.

    2016-01-01

    The mammalian olfactory bulb (OB) displays robust activity-dependent plasticity throughout life. Dopaminergic (DA) neurons in the glomerular layer (GL) of the OB are particularly plastic, with loss of sensory input rapidly reducing tyrosine hydroxylase (TH) expression and dopamine production, followed by a substantial reduction in DA neuron number. Here, we asked whether microglia participate in activity-dependent elimination of DA neurons in the mouse OB. Interestingly, we found a significant reduction in the number of both DA neurons and their synapses in the OB ipsilateral to the occluded naris (occluded OB) within just 7 days of sensory deprivation. Concomitantly, the volume of the occluded OB decreased, resulting in an increase in microglial density. Microglia in the occluded OB also adopted morphologies consistent with activation. Using in vivo 2-photon imaging and histological analysis we then showed that loss of olfactory input markedly altered microglial-neuronal interactions during the time that DA neurons are being eliminated: both microglial process motility and the frequency of wrapping of DA neuron somata by activated microglia increased significantly in the occluded OB. Furthermore, we found microglia in the occluded OB that had completely engulfed components of DA neurons. Together, our data provide evidence that loss of olfactory input modulates microglial-DA neuron interactions in the OB, thereby suggesting an important role for microglia in the activity-dependent elimination of DA neurons and their synapses. PMID:27471450

  14. Olfactory Sensory Activity Modulates Microglial-Neuronal Interactions during Dopaminergic Cell Loss in the Olfactory Bulb.

    PubMed

    Grier, Bryce D; Belluscio, Leonardo; Cheetham, Claire E J

    2016-01-01

    The mammalian olfactory bulb (OB) displays robust activity-dependent plasticity throughout life. Dopaminergic (DA) neurons in the glomerular layer (GL) of the OB are particularly plastic, with loss of sensory input rapidly reducing tyrosine hydroxylase (TH) expression and dopamine production, followed by a substantial reduction in DA neuron number. Here, we asked whether microglia participate in activity-dependent elimination of DA neurons in the mouse OB. Interestingly, we found a significant reduction in the number of both DA neurons and their synapses in the OB ipsilateral to the occluded naris (occluded OB) within just 7 days of sensory deprivation. Concomitantly, the volume of the occluded OB decreased, resulting in an increase in microglial density. Microglia in the occluded OB also adopted morphologies consistent with activation. Using in vivo 2-photon imaging and histological analysis we then showed that loss of olfactory input markedly altered microglial-neuronal interactions during the time that DA neurons are being eliminated: both microglial process motility and the frequency of wrapping of DA neuron somata by activated microglia increased significantly in the occluded OB. Furthermore, we found microglia in the occluded OB that had completely engulfed components of DA neurons. Together, our data provide evidence that loss of olfactory input modulates microglial-DA neuron interactions in the OB, thereby suggesting an important role for microglia in the activity-dependent elimination of DA neurons and their synapses. PMID:27471450

  15. Molecular Mechanisms Regulating the Dendritic Development of Newborn Olfactory Bulb Interneurons in a Sensory Experience-Dependent Manner

    PubMed Central

    Yoshihara, Sei-ichi; Takahashi, Hiroo; Tsuboi, Akio

    2016-01-01

    Inhibitory interneurons in the olfactory bulb are generated continuously throughout life in the subventricular zone and differentiate into periglomerular and granule cells. Neural circuits that undergo reorganization by newborn olfactory bulb interneurons are necessary for odor detection, odor discrimination, olfactory memory, and innate olfactory responses. Although sensory experience has been shown to regulate development in a variety of species and in various structures, including the retina, cortex, and hippocampus, little is known about how sensory experience regulates the dendritic development of newborn olfactory bulb interneurons. Recent studies revealed that the 5T4 oncofetal trophoblast glycoprotein and the neuronal Per/Arnt/Sim domain protein 4 (Npas4) transcription factor regulate dendritic branching and dendritic spine formation, respectively, in olfactory bulb interneurons. Here, we summarize the molecular mechanisms that underlie the sensory input-dependent development of newborn interneurons and the formation of functional neural circuitry in the olfactory bulb. PMID:26793053

  16. Histone acetylation in the olfactory bulb of young rats facilitates aversive olfactory learning and synaptic plasticity.

    PubMed

    Wang, Y-J; Okutani, F; Murata, Y; Taniguchi, M; Namba, T; Kaba, H

    2013-03-01

    Epigenetic mechanisms play an important role in memory formation and synaptic plasticity. Specifically, histone-associated heterochromatin undergoes changes in structure during the early stages of long-term memory formation. In keeping with the classical conditioning paradigm, young rats have been shown to exhibit aversion to an odor stimulus initially presented during foot shock. We previously showed that synaptic plasticity at the dendrodendritic synapses between mitral and granule cells in the olfactory bulb (OB) underlies this aversive olfactory learning. However, the epigenetic mechanisms involved are not well characterized. Therefore, we examined whether intrabulbar infusion of trichostatin A (TSA), a histone deacetylase inhibitor, facilitates olfactory learning in young rats. TSA infusion during odor-shock training enhanced a conditioned odor aversion in a dose-dependent manner and prolonged the learned aversion. Western blot and immunohistochemical analyses showed that the level of histone H4 acetylation significantly increased until 4 h after odor-shock training in both mitral and granule cells in the OB, whereas histone H3 acetylation returned to the control level at 2 h after the training. We also obtained evidence that TSA infusion elevated acetylation of histone H4 or H3. Furthermore, in vitro electrophysiological analysis using slices of the OB revealed that application of TSA significantly enhanced the long-term potentiation induced in synaptic transmission from mitral to granule cells at dendrodendritic synapses. Taken together, these results provide evidence that histone H4 and H3 acetylation in the OB is an epigenetic mechanism associated with aversive olfactory learning in young rats.

  17. Olfactory bulb and retrobulbar regions in the hedgehog tenrec: organization and interconnections.

    PubMed

    Radtke-Schuller, S; Künzle, H

    2000-08-01

    The Madagascan lesser hedgehog tenrec (Echinops telfairi) is a terrestrial, nocturnal insectivore with a low encephalization index and a huge olfactory bulb. To gain insight into the organization and evolution of olfactory regions in placental mammals, the cytoarchitecture (Nissl), neurochemical attributes [zinc and acetylcholinesterase stain, nicotinamide adenine dinucleotide phosphate (NADPh)-diaphorase, and calcium-binding proteins], and interconnections (injections of wheat germ agglutinin-horseradish peroxidase and biotinylated dextran amine) of tenrec bulbar and retrobulbar regions were examined. The tenrec has a well-laminated main olfactory bulb, and modified (atypical) glomeruli are found that, to date, have been demonstrated only in murine rodents. Compared with the main olfactory bulb, the accessory bulb is relatively small, with clearly different staining characteristics, particularly with respect to NADPh-diaphorase, anticalbindin, and anticalretinin. External and central anterior olfactory nuclei also show characteristic cytoarchitectural and chemoarchitectural features. The medial olfactory peduncle seems to differ considerably from that in rodents. A small taenial structure can be separated from the hippocampal continuation. This taenia tecti presumably corresponds to the superior part of the tenia tecti in rodents, but no homologue of the rodent's prominent inferior taenia tecti could be found. The connections of bulbar and retrobulbar regions are similar to those seen in other mammals. Interbulbar projection systems connect the two olfactory bulbs through an external (topographic) and central (nontopographic) anterior nucleus; however, the topographic arrangement of the intrabulbar association system seems to differ from that seen in rodents. A reciprocity of direct olfactory bulb connections with the frontal (sulcal/orbital) cortex was found in the tenrec that has not been reported so far in other species.

  18. Postnatal neurogenesis in the olfactory bulbs of a lizard. A tritiated thymidine autoradiographic study.

    PubMed

    Garcia-Verdugo, J M; Llahi, S; Ferrer, I; Lopez-Garcia, C

    1989-04-10

    Autoradiographically labelled cells were observed in the olfactory bulbs of perinatal, young and adult specimens of the lizard Podarcis hispanica following intraperitoneal injection of tritiated thymidine (5 muCi/g b.wt). After survival times of 7, 18 and 28 days labelled cells were found in the granular layer of both main and accessory bulbs. A few labelled cells were observed in the ependyma, mitral and glomerular layer. In the main olfactory bulb, one week of survival time resulted in labelling of cells in the innermost part of the granular layer. Longer survival times (up to 4 weeks), resulted in labelling of cells mainly in the outermost part of the granular layer. This spatio-temporal gradient was not observed in the accessory bulb. Nevertheless, longer survival times resulted in greater number of labelled cells located in the dorsal and ventral parts of the granular layer of the accessory bulb.

  19. Distribution of vasoactive intestinal polypeptide-like immunoreactivity in the olfactory bulb of the rainbow trout (Salmo gairdneri).

    PubMed

    Alonso, J R; Coveñas, R; Lara, J; de León, M; Aijón, J

    1989-06-26

    The distribution of vasoactive intestinal polypeptide-like structures in the olfactory bulb of the rainbow trout was studied using an indirect-immunoperoxidase technique. Olfactory fibres were very strongly labelled, whereas the fibres or cell bodies in the remaining strata of the olfactory bulb showed no immunoreactivity. In addition, the olfactory nerve fibres were not immunoreactive for methionine- and leucine-enkephalins, motilin, neuropeptide Y, substance P, cholecystokinin-8 and tyrosine-hydroxylase.

  20. Functional neurology of a brain system: a 3D olfactory bulb model to process natural odorants.

    PubMed

    Migliore, Michele; Cavarretta, Francesco; Hines, Michael L; Shepherd, Gordon M

    2013-01-01

    The network of interactions between mitral and granule cells in the olfactory bulb is a critical step in the processing of odor information underlying the neural basis of smell perception. We are building the first computational model in 3 dimensions of this network in order to analyze the rules for connectivity and function within it. The initial results indicate that this network can be modeled to simulate experimental results on the activation of the olfactory bulb by natural odorants, providing a much more powerful approach for 3D simulation of brain neurons and microcircuits.

  1. Tonic and stimulus-evoked nitric oxide production in the mouse olfactory bulb

    PubMed Central

    Lowe, Graeme; Buerk, Donald G.; Ma, Jie; Gelperin, Alan

    2008-01-01

    Nitric oxide (NO) has been long assumed to play a key role in mammalian olfaction. This was based largely on circumstantial evidence, i.e. prominent staining for nitric oxide synthase (NOS) and cyclic GMP or soluble guanylyl cyclase, an effector enzyme activated by NO, in local interneurons of the olfactory bulb. Here we employ innovative custom-fabricated NO micro-sensors to obtain the first direct, time-resolved measurements of NO signaling in the olfactory bulb. In 400 μm thick mouse olfactory bulb slices, we detected a steady average basal level of 87 nM NO in the extracellular space of mitral or granule cell layers. This NO ‘tone’ was sensitive to NOS substrate manipulation (200 μM L-arginine, 2 mM L-NAME) and Mg2+ modulation of NMDA receptor conductance. Electrical stimulation of olfactory nerve fibers evoked transient (peak at 10 s) increments in NO levels 90 – 100 nM above baseline. In the anesthetized mouse, NO micro-sensors inserted into the granule cell layer detected NO transients averaging 55 nM in amplitude and peaking at 3.4 sec after onset of a 5 sec odorant stimulation. These findings suggest dual roles for NO signaling in the olfactory bulb – tonic inhibitory control of principal neurons, and regulation of circuit dynamics during odor information processing. PMID:18407420

  2. Calcium Signaling in Mitral Cell Dendrites of Olfactory Bulbs of Neonatal Rats and Mice during Olfactory Nerve Stimulation and Beta-Adrenoceptor Activation

    ERIC Educational Resources Information Center

    Yuan, Qi; Mutoh, Hiroki; Debarbieux, Franck; Knopfel, Thomas

    2004-01-01

    Synapses formed by the olfactory nerve (ON) provide the source of excitatory synaptic input onto mitral cells (MC) in the olfactory bulb. These synapses, which relay odor-specific inputs, are confined to the distally tufted single primary dendrites of MCs, the first stage of central olfactory processing. Beta-adrenergic modulation of electrical…

  3. Inducible activation of ERK5 MAP kinase enhances adult neurogenesis in the olfactory bulb and improves olfactory function.

    PubMed

    Wang, Wenbin; Lu, Song; Li, Tan; Pan, Yung-Wei; Zou, Junhui; Abel, Glen M; Xu, Lihong; Storm, Daniel R; Xia, Zhengui

    2015-05-20

    Recent discoveries have suggested that adult neurogenesis in the subventricular zone (SVZ) and olfactory bulb (OB) may be required for at least some forms of olfactory behavior in mice. However, it is unclear whether conditional and selective enhancement of adult neurogenesis by genetic approaches is sufficient to improve olfactory function under physiological conditions or after injury. Furthermore, specific signaling mechanisms regulating adult neurogenesis in the SVZ/OB are not fully defined. We previously reported that ERK5, a MAP kinase selectively expressed in the neurogenic regions of the adult brain, plays a critical role in adult neurogenesis in the SVZ/OB. Using a site-specific knock-in mouse model, we report here that inducible and targeted activation of the endogenous ERK5 in adult neural stem/progenitor cells enhances adult neurogenesis in the OB by increasing cell survival and neuronal differentiation. This conditional ERK5 activation also improves short-term olfactory memory and odor-cued associative olfactory learning under normal physiological conditions. Furthermore, these mice show enhanced recovery of olfactory function and have more adult-born neurons after a zinc sulfate-induced lesion of the main olfactory epithelium. We conclude that ERK5 MAP kinase is an important endogenous signaling pathway regulating adult neurogenesis in the SVZ/OB, and that conditional activation of endogenous ERK5 is sufficient to enhance adult neurogenesis in the OB thereby improving olfactory function both under normal conditions and after injury.

  4. Inducible Activation of ERK5 MAP Kinase Enhances Adult Neurogenesis in the Olfactory Bulb and Improves Olfactory Function

    PubMed Central

    Wang, Wenbin; Lu, Song; Li, Tan; Pan, Yung-Wei; Zou, Junhui; Abel, Glen M.; Xu, Lihong; Storm, Daniel R.

    2015-01-01

    Recent discoveries have suggested that adult neurogenesis in the subventricular zone (SVZ) and olfactory bulb (OB) may be required for at least some forms of olfactory behavior in mice. However, it is unclear whether conditional and selective enhancement of adult neurogenesis by genetic approaches is sufficient to improve olfactory function under physiological conditions or after injury. Furthermore, specific signaling mechanisms regulating adult neurogenesis in the SVZ/OB are not fully defined. We previously reported that ERK5, a MAP kinase selectively expressed in the neurogenic regions of the adult brain, plays a critical role in adult neurogenesis in the SVZ/OB. Using a site-specific knock-in mouse model, we report here that inducible and targeted activation of the endogenous ERK5 in adult neural stem/progenitor cells enhances adult neurogenesis in the OB by increasing cell survival and neuronal differentiation. This conditional ERK5 activation also improves short-term olfactory memory and odor-cued associative olfactory learning under normal physiological conditions. Furthermore, these mice show enhanced recovery of olfactory function and have more adult-born neurons after a zinc sulfate-induced lesion of the main olfactory epithelium. We conclude that ERK5 MAP kinase is an important endogenous signaling pathway regulating adult neurogenesis in the SVZ/OB, and that conditional activation of endogenous ERK5 is sufficient to enhance adult neurogenesis in the OB thereby improving olfactory function both under normal conditions and after injury. PMID:25995470

  5. Direct transport of inhaled xylene and its metabolites from the olfactory mucosa to the glomeruli of the olfactory bulbs

    SciTech Connect

    Lewis, J.L.; Dahl, A.R.; Kracko, D.A.

    1994-11-01

    The olfactory epithelium is a unique tissue in that single receptor neurons have dendrites in contact with the external environment at the nasal airway, and axon terminals that penetrate the cribriform plate and synapse in the olfactory bulb. The Central Nervous System (CNS) is protected from systematically circulating toxicants by a blood-brain barrier primarily composed of tight junctions between endothelial cells in cerebral vessels and a high metabolic capacity within these cells. No such barrier has yet been defined to protect the CNS from inhaled toxicants. Because all inhalants do not seem to access the CNS directly, a nose-brain barrier seems plausible. The purpose of the work described here is to determine whether or not a nose-brain barrier exists and to define its components. Although such a barrier is likely to be multi-faceted, the present work focuses only on the importance of gross histologic and metabolic characteristics of the olfactory epithelium in olfactory transport.

  6. Olfactory hallucinations elicited by electrical stimulation via subdural electrodes: effects of direct stimulation of olfactory bulb and tract.

    PubMed

    Kumar, Gogi; Juhász, Csaba; Sood, Sandeep; Asano, Eishi

    2012-06-01

    In 1954, Penfield and Jasper briefly described that percepts of unpleasant odor were elicited by intraoperative electrical stimulation of the olfactory bulb in patients with epilepsy. Since then, few peer-reviewed studies have reported such phenomena elicited by stimulation mapping via subdural electrodes implanted on the ventral surface of the frontal lobe. Here, we determined what types of olfactory hallucinations could be reproduced by such stimulation in children with focal epilepsy. This study included 16 children (age range: 5 to 17 years) who underwent implantation of subdural electrodes to localize the presumed epileptogenic zone and eloquent areas. Pairs of electrodes were electrically stimulated, and clinical responses were observed. In case a patient reported a perception, she/he was asked to describe its nature. We also described the stimulus parameters to elicit a given symptom. Eleven patients reported a perception of smell in response to electrical stimulation while the remaining five did not. Nine patients perceived an unpleasant smell (like bitterness, smoke, or garbage) while two perceived a pleasant smell (like strawberry or good food). Such olfactory hallucinations were induced by stimulation proximal to the olfactory bulb or tract on either hemisphere but not by that of orbitofrontal gyri lateral to the medial orbital sulci. The range of stimulus parameters employed to elicit olfactory hallucinations was comparable to those for other sensorimotor symptoms. Our systematic study of children with epilepsy replicated stimulation-induced olfactory hallucinations. We failed to provide evidence that a positive olfactory perception could be elicited by conventional stimulation of secondary olfactory cortex alone.

  7. Trajectory and terminal distribution of single centrifugal axons from olfactory cortical areas in the rat olfactory bulb.

    PubMed

    Matsutani, S

    2010-08-11

    The olfactory bulb receives a large number of centrifugal fibers whose functions remain unclear. To gain insight into the function of the bulbar centrifugal system, the morphology of individual centrifugal axons from olfactory cortical areas was examined in detail. An anterograde tracer, Phaseolus vulgaris leucoagglutinin, was injected into rat olfactory cortical areas, including the pars lateralis of the anterior olfactory nucleus (lAON) and the anterior part of the piriform cortex (aPC). Reconstruction from serial sections revealed that the extrabulbar segments of centrifugal axons from the lAON and those from the aPC had distinct trajectories: the former tended to innervate the pars externa of the AON before entering the olfactory bulb, while the latter had extrabulbar collaterals that extended to a variety of targets. In contrast to the extrabulbar segments, no clear differences were found between the intrabulbar segments of axons from the lAON and from the aPC. The intrabulbar segments of centrifugal axons were mainly found in the granule cell layer but a few axons extended into the external plexiform and glomerular layer. Approximately 40% of centrifugal axons innervated both the medial and lateral aspects of the olfactory bulb. The number of boutons found on single intrabulbar segments was typically less than 1000. Boutons tended to aggregate and form complex terminal tufts with short axonal branches. Terminal tufts, no more than 10 in single axons from ipsilateral cortical areas, were localized to the granule cell layer with varying intervals; some tufts formed patchy clusters and others were scattered over areas that extended for a few millimeters. The patchy, widespread distribution of terminals suggests that the centrifugal axons are able to couple the activity of specific subsets of bulbar neurons even when the subsets are spatially separated.

  8. Inhibition of Olfactory Receptor Neuron Input to Olfactory Bulb Glomeruli Mediated by Suppression of Presynaptic Calcium Influx

    PubMed Central

    Wachowiak, Matt; McGann, John P.; Heyward, Philip M.; Shao, Zuoyi; Puche, Adam C.; Shipley, Michael T.

    2005-01-01

    We investigated the cellular mechanism underlying presynaptic regulation of olfactory receptor neuron (ORN) input to the mouse olfactory bulb using optical-imaging techniques that selectively report activity in the ORN pre-synaptic terminal. First, we loaded ORNs with calcium-sensitive dye and imaged stimulus-evoked calcium influx in a slice preparation. Single olfactory nerve shocks evoked rapid fluorescence increases that were largely blocked by the N-type calcium channel blocker ω-conotoxin GVIA. Paired shocks revealed a long-lasting suppression of calcium influx with ~40% suppression at 400-ms interstimulus intervals and a recovery time constant of ~450 ms. Blocking activation of postsynaptic olfactory bulb neurons with APV/CNQX reduced this suppression. The GABAB receptor agonist baclofen inhibited calcium influx, whereas GABAB antagonists reduced paired-pulse suppression without affecting the response to the conditioning pulse. We also imaged transmitter release directly using a mouse line that expresses synaptopHluorin selectively in ORNs. We found that the relationship between calcium influx and transmitter release was superlinear and that paired-pulse suppression of transmitter release was reduced, but not eliminated, by APV/CNQX and GABAB antagonists. These results demonstrate that primary olfactory input to the CNS can be presynaptically regulated by GABAergic interneurons and show that one major intracellular pathway for this regulation is via the suppression of calcium influx through N-type calcium channels in the pre-synaptic terminal. This mechanism is unique among primary sensory afferents. PMID:15917320

  9. Comment on "Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension".

    PubMed

    Sanai, Nader; Berger, Mitchel S; Garcia-Verdugo, Jose Manuel; Alvarez-Buylla, Arturo

    2007-10-19

    Curtis et al. (Research Articles, 2 March 2007, p. 1243) claimed discovery of a human neuronal migratory stream to the olfactory bulb along a putative lateral ventricular extension. However, high levels of proliferation reported with proliferating cell nuclear antigen were not confirmed using different markers, neuronal chain migration was not demonstrated, and no serial reconstruction shows a true ventricular extension.

  10. Adult Olfactory Bulb Interneuron Phenotypes Identified by Targeting Embryonic and Postnatal Neural Progenitors

    PubMed Central

    Figueres-Oñate, Maria; López-Mascaraque, Laura

    2016-01-01

    Neurons are generated during embryonic development and in adulthood, although adult neurogenesis is restricted to two main brain regions, the hippocampus and olfactory bulb. The subventricular zone (SVZ) of the lateral ventricles generates neural stem/progenitor cells that continually provide the olfactory bulb (OB) with new granule or periglomerular neurons, cells that arrive from the SVZ via the rostral migratory stream. The continued neurogenesis and the adequate integration of these newly generated interneurons is essential to maintain homeostasis in the olfactory bulb, where the differentiation of these cells into specific neural cell types is strongly influenced by temporal cues. Therefore, identifying the critical features that control the generation of adult OB interneurons at either pre- or post-natal stages is important to understand the dynamic contribution of neural stem cells. Here, we used in utero and neonatal SVZ electroporation along with a transposase-mediated stable integration plasmid, in order to track interneurons and glial lineages in the OB. These plasmids are valuable tools to study the development of OB interneurons from embryonic and post-natal SVZ progenitors. Accordingly, we examined the location and identity of the adult progeny of embryonic and post-natally transfected progenitors by examining neurochemical markers in the adult OB. These data reveal the different cell types in the olfactory bulb that are generated in function of age and different electroporation conditions. PMID:27242400

  11. Value of MRI olfactory bulb evaluation in the assessment of olfactory dysfunction in Bardet-Biedl syndrome.

    PubMed

    Braun, J J; Noblet, V; Kremer, S; Molière, S; Dollfus, H; Marion, V; Goetz, N; Muller, J; Riehm, S

    2016-07-01

    Olfactory bulb (OB) volume evaluation by magnetic resonance imaging (MRI) has been demonstrated to be related to olfactory dysfunction in many different diseases. Olfactory dysfunction is often overlooked in Bardet-Biedl syndrome (BBS) patients and is rarely objectively evaluated by MRI. We present a series of 20 BBS patients with olfactory dysfunction. The OB was evaluated separately and blindly by two radiologists (SR and SM) with 3 Tesla MRI imaging comparatively to 12 normal control subjects by global visual evaluation and by quantitative measurement of OB volume. In the 12 control cases OB visual evaluation was considered as normal in all cases for radiologist (SR) and in 10 cases for radiologist (SM). In the 20 BBS patients, OB visual evaluation was considered as abnormal in 18 cases for SR and in all cases for SM. OB volumetric evaluation for SR and SM in BBS patients was able to provide significant correlation between BBS and olfactory dysfunction. This study indicates that OB volume evaluation by MRI imaging like structural MRI scan for gray matter modifications demonstrates that olfactory dysfunction in BBS patients is a constant and cardinal symptom integrated in a genetical syndrome with peripheral and central olfactory structure alterations.

  12. Circuit formation and function in the olfactory bulb of mice with reduced spontaneous afferent activity.

    PubMed

    Lorenzon, Paolo; Redolfi, Nelly; Podolsky, Michael J; Zamparo, Ilaria; Franchi, Sira Angela; Pietra, Gianluca; Boccaccio, Anna; Menini, Anna; Murthy, Venkatesh N; Lodovichi, Claudia

    2015-01-01

    The type of neuronal activity required for circuit development is a matter of significant debate. We addressed this issue by analyzing the topographic organization of the olfactory bulb in transgenic mice engineered to have very little afferent spontaneous activity due to the overexpression of the inwardly rectifying potassium channel Kir2.1 in the olfactory sensory neurons (Kir2.1 mice). In these conditions, the topography of the olfactory bulb was unrefined. Odor-evoked responses were readily recorded in glomeruli with reduced spontaneous afferent activity, although the functional maps were coarser than in controls and contributed to altered olfactory discrimination behavior. In addition, overexpression of Kir2.1 in adults induced a regression of the already refined connectivity to an immature (i.e., coarser) status. Our data suggest that spontaneous activity plays a critical role not only in the development but also in the maintenance of the topography of the olfactory bulb and in sensory information processing. PMID:25568110

  13. Efferent and afferent connections of the olfactory bulb and prepiriform cortex in the pigeon (Columba livia).

    PubMed

    Atoji, Yasuro; Wild, J Martin

    2014-06-01

    Although olfaction in birds is known to be involved in a variety of behaviors, there is comparatively little detailed information on the olfactory brain. In the pigeon brain, the olfactory bulb (OB) is known to project to the prepiriform cortex (CPP), piriform cortex (CPi), and dorsolateral corticoid area (CDL), which together are called the olfactory pallium, but centrifugal pathways to the OB have not been fully explored. Fiber connections of CPi and CDL have been reported, but those of other olfactory pallial nuclei remain unknown. The present study examines the fiber connections of OB and CPP in pigeons to provide a more detailed picture of their connections using tract-tracing methods. When anterograde and retrograde tracers were injected in OB, projections to a more extensive olfactory pallium were revealed, including the anterior olfactory nucleus, CPP, densocellular part of the hyperpallium, tenia tecta, hippocampal continuation, CPi, and CDL. OB projected commissural fibers to the contralateral OB but did not receive afferents from the contralateral olfactory pallium. When tracers were injected in CPP, reciprocal ipsilateral connections with OB and nuclei of the olfactory pallium were observed, and CPP projected to the caudolateral nidopallium and the limbic system, including the hippocampal formation, septum, lateral hypothalamic nucleus, and lateral mammillary nucleus. These results show that the connections of OB have a wider distribution throughout the olfactory pallium than previously thought and that CPP provides a centrifugal projection to the OB and acts as a relay station to the limbic system.

  14. Cluster Analysis of the Rat Olfactory Bulb Activity in Response to Different Odorants

    NASA Astrophysics Data System (ADS)

    Falasconi, M.; Gutierrez, A.; Auffarth, B.; Sberveglieri, G.; Marco, S.

    2009-05-01

    With the goal of deepen in the understanding of coding of chemical information in the olfactory system, a large data set consisting of rat's olfactory bulb activity values in response to several different volatile compounds has been analyzed by fuzzy c-means clustering methods. Clustering should help to discover groups of glomeruli that are similary activated according to their response profiles across the odorants. To investigate the significance of the achieved fuzzy partitions we developed and applied a novel validity approach based on cluster stability. Our results show certain level of glomerular clustering in the olfactory bulb and indicate that exist a main chemo-topic subdivision of the glomerular layer in few macro-area which are rather specific to particular functional groups of the volatile molecules.

  15. Mesenchymal stem cells from rat olfactory bulbs can differentiate into cells with cardiomyocyte characteristics.

    PubMed

    Huang, Yuahn-Sieh; Li, I-Hsun; Chueh, Sheau-Huei; Hueng, Dueng-Yuan; Tai, Ming-Cheng; Liang, Chang-Min; Lien, Shiu-Bii; Sytwu, Huey-Kang; Ma, Kuo-Hsing

    2015-12-01

    Mesenchymal stromal/stem cells (MSCs) are widely distributed in different tissues such as bone marrow, adipose tissues, peripheral blood, umbilical cord and amnionic fluid. Recently, MSC-like cells were also found to exist in rat olfactory bulb and are capable of inducing differentiation into mesenchymal lineages - osteocytes, chondrocytes and adipocytes. However, whether these cells can differentiate into myocardial cells is not known. In this study, we examined whether olfactory bulb-derived MSCs could differentiate into myocardial cells in vitro. Fibroblast-like cells isolated from the olfactory bulb of neonatal rats were grown under four conditions: no treatment; in the presence of growth factors (neuregulin-1, bFGF and forskolin); co-cultured with cardiomyocytes; and co-cultured with cardiomyocytes plus neuregulin-1, bFGF and forskolin. Cell differentiation into myocardial cells was monitored by RT-PCR, light microscopy immunofluorescence, western blot analysis and contractile response to pharmacological treatments. The isolated olfactory bulb-derived fibroblast-like cells expressed CD29, CD44, CD90, CD105, CD166 but not CD34 and CD45, consistent with the characteristics of MSCs. Long cylindical cells that spontaneously contracted were only observed following 7 days of co-culture of MSCs with rat cardiomyocytes plus neuregulin-1, bFGF and forskolin. RT-PCR and western blot analysis indicated that the cylindrical cells expressed myocardial markers, such as Nkx2.5, GATA4, sarcomeric α-actinin, cardiac troponin I, cardiac myosin heavy chain, atrial natriuretic peptide and connexin 43. They also contained sarcomeres and gap junction and were sensitive to pharmacological treatments (adrenal and cholinergic agonists and antagonists). These findings indicate that rat olfactory bulb-derived fibroblast-like cells with MSC characteristics can differentiate into myocardial-like cells.

  16. Influence of the olfactory bulbs on blood leukocytes and behavioral responses to infection in Siberian hamsters.

    PubMed

    Prendergast, Brian J; Galang, Jerome; Kay, Leslie M; Pyter, Leah M

    2009-05-01

    Surgical removal of the olfactory bulb alters several aspects of immunological activity. This study investigated the role of the olfactory bulbs in the control of behavioral responses to simulated infection, and the environmental modulation of sickness behaviors by changes in day length. Adult male Siberian hamsters (Phodopus sungorus) were subjected to bilateral olfactory bulbectomy (OBx) or a sham surgical procedure, and were then exposed to long(15 h light/day; LD) or short (9 h light/day; SD) photoperiods for 8–12 weeks, after which circulating leukocytes and behavioral responses (anorexia, anhedonia, cachexia) to simulated gram-negative bacterial infections (i.p. lipopolysaccharide [LPS] treatment;0.625 mg/kg) were quantified. OBx treatment altered the effects of photoperiod on immune function in a trait-specific manner. LPS-induced anorexia was exacerbated in SD-OBx hamsters; LPS-induced anhedonia was exacerbated in LD-OBx hamsters; and photoperiodic differences in circulating leukocytes and LPS-induced cachexia were eliminated by OBx. Plasma cortisol concentrations did not differ between LD and SD hamsters, irrespective of olfactory bulb integrity. The data indicate that photoperiod affects immune function via OB-dependent and -independent mechanisms, and that changes in cortisol production are not required for photoperiodic changes in sickness behaviors to manifest.

  17. Absence of mitral cells in monolayer in monotremes. Variations in vertebrate olfactory bulbs.

    PubMed

    Switzer, R C; Johnson, J I

    1977-01-01

    An invariant feature of the olfactory bulb in placental and marsupial mammals is the arrangement of the perikarya of mitral cells in a monolayer. Contrasting with this is the arrangement found in the olfactory bulbs of the monotremes, platypus and echidna, where the large perikarya are not only absent from the position of a monolayer (usually forming the external boundary of the internal plexiform layer) but occupy a region which would characterize them as tufted cells. In other classes of amniote vertebrates, reptiles and birds, the placement of large perikarya in the olfactory bulb ranges from a compact layer to a broad band. Such an overview among several vertebrate classes suggests that a monolayer of mitral cells may be a specialized subset of the tufted-mitral cell population. The accessory olfactory formation among mammals also exhibits variation in the compactness of the large perikarya: a broadband in most but a compact layer in a few others such as the chinchilla and the capybara. Such specialized alignment of perikarya (and, consequently, of their dendritic and axonal elements) may enable more refined signal processing than does random alignment of these elements. Such speculations can be tested using appropriate phylogenetic sampling, and monotremes provide particularly advantageous test cases. PMID:899683

  18. Absence of mitral cells in monolayer in monotremes. Variations in vertebrate olfactory bulbs.

    PubMed

    Switzer, R C; Johnson, J I

    1977-01-01

    An invariant feature of the olfactory bulb in placental and marsupial mammals is the arrangement of the perikarya of mitral cells in a monolayer. Contrasting with this is the arrangement found in the olfactory bulbs of the monotremes, platypus and echidna, where the large perikarya are not only absent from the position of a monolayer (usually forming the external boundary of the internal plexiform layer) but occupy a region which would characterize them as tufted cells. In other classes of amniote vertebrates, reptiles and birds, the placement of large perikarya in the olfactory bulb ranges from a compact layer to a broad band. Such an overview among several vertebrate classes suggests that a monolayer of mitral cells may be a specialized subset of the tufted-mitral cell population. The accessory olfactory formation among mammals also exhibits variation in the compactness of the large perikarya: a broadband in most but a compact layer in a few others such as the chinchilla and the capybara. Such specialized alignment of perikarya (and, consequently, of their dendritic and axonal elements) may enable more refined signal processing than does random alignment of these elements. Such speculations can be tested using appropriate phylogenetic sampling, and monotremes provide particularly advantageous test cases.

  19. Participation of the Olfactory Bulb in Circadian Organization during Early Postnatal Life in Rabbits

    PubMed Central

    Navarrete, Erika; Ortega-Bernal, Juan Roberto; Trejo-Muñoz, Lucero; Díaz, Georgina; Montúfar-Chaveznava, Rodrigo; Caldelas, Ivette

    2016-01-01

    Experimental evidence indicates that during pre-visual stages of development in mammals, circadian regulation is still not under the control of the light-entrainable hypothalamic pacemaker, raising the possibility that the circadian rhythmicity that occurs during postnatal development is under the control of peripheral oscillators, such as the main olfactory bulb (MOB). We evaluated the outcome of olfactory bulbectomy on the temporal pattern of core body temperature and gross locomotor activity in newborn rabbits. From postnatal day 1 (P1), pups were randomly assigned to one of the following conditions: intact pups (INT), intact pups fed by enteral gavage (INT+ENT), sham operated pups (SHAM), pups with unilateral lesions of the olfactory bulb (OBx-UNI), and pups with bilateral lesions of the olfactory bulb (OBx-BI). At the beginning of the experiment, from P1-8, the animals in all groups were fed at 11:00, from P9-13 the feeding schedule was delayed 6 h (17:00), and finally, from P14-15 the animals were subjected to fasting conditions. The rabbit pups of the INT, INT+ENT, SHAM and OBx-UNI groups exhibited a clear circadian rhythmicity in body temperature and locomotor activity, with a conspicuous anticipatory rise hours prior to the nursing or feeding schedule, which persisted even during fasting conditions. In addition, phase delays in the nursing or feeding schedule induced a clear phase shift in both parameters. In contrast, the OBx-BI group exhibited atypical rhythmicity in both parameters under entrained conditions that altered the anticipatory component, as well as deficient phase control of both rhythms. The present results demonstrate that the expression of circadian rhythmicity at behavioral and physiological levels during early stages of rabbit development largely depends on the integrity of the main olfactory bulb. PMID:27305041

  20. Participation of the Olfactory Bulb in Circadian Organization during Early Postnatal Life in Rabbits.

    PubMed

    Navarrete, Erika; Ortega-Bernal, Juan Roberto; Trejo-Muñoz, Lucero; Díaz, Georgina; Montúfar-Chaveznava, Rodrigo; Caldelas, Ivette

    2016-01-01

    Experimental evidence indicates that during pre-visual stages of development in mammals, circadian regulation is still not under the control of the light-entrainable hypothalamic pacemaker, raising the possibility that the circadian rhythmicity that occurs during postnatal development is under the control of peripheral oscillators, such as the main olfactory bulb (MOB). We evaluated the outcome of olfactory bulbectomy on the temporal pattern of core body temperature and gross locomotor activity in newborn rabbits. From postnatal day 1 (P1), pups were randomly assigned to one of the following conditions: intact pups (INT), intact pups fed by enteral gavage (INT+ENT), sham operated pups (SHAM), pups with unilateral lesions of the olfactory bulb (OBx-UNI), and pups with bilateral lesions of the olfactory bulb (OBx-BI). At the beginning of the experiment, from P1-8, the animals in all groups were fed at 11:00, from P9-13 the feeding schedule was delayed 6 h (17:00), and finally, from P14-15 the animals were subjected to fasting conditions. The rabbit pups of the INT, INT+ENT, SHAM and OBx-UNI groups exhibited a clear circadian rhythmicity in body temperature and locomotor activity, with a conspicuous anticipatory rise hours prior to the nursing or feeding schedule, which persisted even during fasting conditions. In addition, phase delays in the nursing or feeding schedule induced a clear phase shift in both parameters. In contrast, the OBx-BI group exhibited atypical rhythmicity in both parameters under entrained conditions that altered the anticipatory component, as well as deficient phase control of both rhythms. The present results demonstrate that the expression of circadian rhythmicity at behavioral and physiological levels during early stages of rabbit development largely depends on the integrity of the main olfactory bulb. PMID:27305041

  1. Patterns of olfactory bulb neurogenesis in the adult zebrafish are altered following reversible deafferentation.

    PubMed

    Trimpe, Darcy M; Byrd-Jacobs, Christine A

    2016-09-01

    Adult brain plasticity can be investigated using reversible methods that remove afferent innervation but allow return of sensory input. Repeated intranasal irrigation with Triton X-100 in adult zebrafish diminishes innervation to the olfactory bulb, resulting in a number of alterations in bulb structure and function, and cessation of the treatment allows for reinnervation and recovery. Using bromodeoxyuridine, Hu, and caspase-3 immunoreactivity we examined cell proliferation, differentiation, migration, and survival under conditions of acute and chronic deafferentation and reafferentation. Cell proliferation within the olfactory bulb was not influenced by acute or chronic deafferentation or reafferentation, but cell fate (including differentiation, migration, and/or survival of newly formed cells) was affected. We found that chronic deafferentation caused a bilateral increase in the number of newly formed cells that migrated into the bulb, although the amount of cell death of these new cells was significantly increased compared to untreated fish. Reafferentation also increased the number of newly formed cells migrating into both bulbs, suggesting that the deafferentation effect on cell fate was maintained. Reafferentation resulted in a decrease in newly formed cells that became neurons and, although death of newly formed cells was not altered from control levels, survival was reduced in relation to that seen in chronically deafferented fish. The potential effect of age on cell genesis was also examined. While the amount of cell migration into the olfactory bulbs was not affected by fish age, more of the newly formed cells became neurons in older fish. Younger fish displayed more cell death under conditions of chronic deafferentation. In sum, our results show that reversible deafferentation affects several aspects of cell fate, including cell differentiation, migration, and survival, and age of the fish influences the response to deafferentation. PMID:27343831

  2. Subtype-specific reduction of olfactory bulb interneurons in Pax6 heterozygous mutant mice.

    PubMed

    Haba, Hasumi; Nomura, Tadashi; Suto, Fumikazu; Osumi, Noriko

    2009-09-01

    Interneurons in the olfactory bulb (OB) play essential roles in the processing of olfactory information. They are classified into several subpopulations by the expression of different neurochemical markers. Here we focused on a transcription factor Pax6, and examined its expression and function in distinct subtypes of OB interneurons. We identified Pax6 expression in specific subtypes of interneurons in the external plexiform layer (EPL). The number of these interneuron subtypes was dramatically decreased in Pax6 heterozygous mutant mice. These results indicate that Pax6 is required for differentiation and/or maintenance of EPL interneurons in the adult mouse OB.

  3. Precise Detection of Direct Glomerular Input Duration by the Olfactory Bulb

    PubMed Central

    Li, Anan; Gire, David H.; Bozza, Thomas

    2014-01-01

    Sensory neuron input to the olfactory bulb (OB) was activated precisely for different durations with blue light in mice expressing channelrhodopsin-2 in olfactory sensory neurons. Behaviorally the mice discriminated differences of 10 ms in duration of direct glomerular activation. In addition, a subset of mitral/tufted cells in the OB of awake mice responded tonically therefore conveying information on stimulus duration. Our study provides evidence that duration of the input to glomeruli not synchronized to sniffing is detected. This potent cue may be used to obtain information on puffs in odor plumes. PMID:25429146

  4. Early life stress disrupts attachment learning: The role of amygdala corticosterone, locus coeruleus CRH and olfactory bulb NE

    PubMed Central

    Moriceau, Stephanie; Shionoya, Kiseko; Jakubs, Katherine; Sullivan, Regina M.

    2010-01-01

    Infant rats require maternal odor learning to guide pups proximity-seeking of the mother and nursing. Maternal odor learning occurs using a simple learning circuit including robust olfactory bulb norepinephrine (NE) release from the locus coeruleus (LC) and amygdala suppression by low corticosterone (CORT). Early life stress increases NE but also CORT and we questioned whether early life stress disrupted attachment learning and its neural correlates (2-DG autoradiography). Neonatal rats were normally-reared or stressed-reared during the first 6-days of life by providing the mother with insufficient bedding for nest building and were odor-0.5mA shock conditioned at 7-day old. Normally-reared paired pups exhibited typical odor approach learning and associated olfactory bulb enhanced 2-DG uptake. However, stressed-reared pups showed odor avoidance learning and both olfactory bulb and amygdala 2-DG uptake enhancement. Furthermore, stressed-reared pups had elevated CORT levels and systemic CORT antagonist injection reestablished the age appropriate odor preference learning, enhanced olfactory bulb and attenuated amygdala 2-DG. We also assessed the neural mechanism for stressed-reared pups' abnormal behavior in a more controlled environment by injecting normally-reared pups with CORT. This was sufficient to produce odor aversion, as well as dual amygdala and olfactory bulb enhanced 2-DG uptake. Moreover, we assessed a unique cascade of neural events for the aberrant effects of stress rearing: the amygdala-LC-olfactory bulb pathway. Intra-amygdala CORT or intra-LC corticotropin releasing hormone (CRH) infusion supported aversion learning with intra-LC CRH infusion associated with increased olfactory bulb NE (microdialysis). These results suggest that early life stress disturbs attachment behavior via a unique cascade of events (amygdala-LC-olfactory bulb). PMID:20016090

  5. Invasive sinonasal adenocarcinoma with an absent olfactory bulb: a case report

    PubMed Central

    Newman, Thomas H.; Tipper, Geoffrey A.; Hussain, Zakier

    2016-01-01

    Sinonasal adenocarcinomas are rare, locally invasive tumours. In this case the symptomatic profile was unusual and the diagnosis was missed at the primary care stage. Interestingly this would be the first documented case with an absent ipsilateral olfactory bulb. A 55-year old male presented with symptoms of behavioural change and mild headaches. He was later found to have a large Sinonasal adenocarcinoma which penetrated the skull base. This was treated by a combined craniotomy and endonasal approach. Sinonasal adenocarcinomas are unusual tumours and further research is required in order to clarify management strategies and prognosis. This interesting case was more unusual again given its presentation, extent and absence of the olfactory bulb. Importantly for primary care physicians the initial diagnosis was considered psychiatric rather than organic; despite there being specific features of the presentation which were suggestive of an intra-cranial lesion. PMID:27402540

  6. Cerebral complexity preceded enlarged brain size and reduced olfactory bulbs in Old World monkeys

    PubMed Central

    Gonzales, Lauren A.; Benefit, Brenda R.; McCrossin, Monte L.; Spoor, Fred

    2015-01-01

    Analysis of the only complete early cercopithecoid (Old World monkey) endocast currently known, that of 15-million-year (Myr)-old Victoriapithecus, reveals an unexpectedly small endocranial volume (ECV) relative to body size and a large olfactory bulb volume relative to ECV, similar to extant lemurs and Oligocene anthropoids. However, the Victoriapithecus brain has principal and arcuate sulci of the frontal lobe not seen in the stem catarrhine Aegyptopithecus, as well as a distinctive cercopithecoid pattern of gyrification, indicating that cerebral complexity preceded encephalization in cercopithecoids. Since larger ECVs, expanded frontal lobes, and reduced olfactory bulbs are already present in the 17- to 18-Myr-old ape Proconsul these features evolved independently in hominoids (apes) and cercopithecoids and much earlier in the former. Moreover, the order of encephalization and brain reorganization was apparently different in hominoids and cercopithecoids, showing that brain size and cerebral organization evolve independently. PMID:26138795

  7. Sexual dimorphism in accessory olfactory bulb mitral cells: a quantitative Golgi study.

    PubMed

    Caminero, A A; Segovia, S; Guillamón, A

    1991-01-01

    The purpose of the present study was to identify the existence of sexual dimorphism in the dendritic field of accessory olfactory bulb mitral cells in rats and to investigate the effects of male orchidectomy and female androgenization on the day of birth upon this dendritic field. The rapid Golgi method was used to conduct a quantitative study of various characteristics of the dendritic field of accessory olfactory bulb mitral cells. The results indicated greater values for males than females for the following characteristics: (i) somatic area; (ii) degree of branching in the dendritic field; (iii) total dendritic length; and (iv) dendritic density around the neuronal soma. Orchidectomy of males, as well as androgenization of females, on the day of birth inverted these differences.

  8. Morphological variations among output neurons of the olfactory bulb in the frog (Rana ridibunda).

    PubMed

    Jiang, T; Holley, A

    1992-06-01

    Morphological properties of putative output cells have been studied in detail in the olfactory bulb of frogs (Rana ridibunda). Intracellular injection of Lucifer Yellow was used to reconstruct individual neurons. Ten different anatomical features related to cell shape and position were studied quantitatively. The results show that output cells, generally considered to be a homogeneous group in the olfactory bulb of amphibians, are, in fact, quite different in their morphology. Using multidimensional analysis to examine differences among the output neurons, we found that they might be divided into at least two groups. In one group, the cell somata were located near the glomerular layer and the dendrites lay at large angles with respect to each other. In the other group, the cell somata were farther from the glomerular layer and their dendrites lay at smaller angles. From their morphology, these two cell groups appear to be homologous, respectively, to the superficial/middle tufted cells and deep tufted/mitral cells of mammals.

  9. Morphologic alteration of the olfactory bulb after acute ozone exposure in rats.

    PubMed

    Colín-Barenque, L; Avila-Costa, M R; Fortoul, T; Rugerio-Vargas, C; Machado-Salas, J P; Espinosa-Villanueva, J; Rivas-Arancibia, S

    1999-10-15

    The interaction of ozone with some molecules results in an increased production of free radicals. The objective of this study was to identify whether acute ozone exposure to 1-1.5 ppm for 4 h, produced cytological and ultrastructural modifications in the olfactory bulb cells. The results showed that in rats exposed to ozone there was a significant loss of dendritic spines on primary and secondary dendrites of granule cells, whereas the control rats did not present such changes. Besides these exposed cells showed vacuolation of neuronal cytoplasm, swelling of Golgi apparatus and mitochondrion, dilation cisterns of the rough endoplasmic reticulum. These findings suggest that oxidative stress produced by ozone induces alterations in the granule layer of the olfactory bulb, which may be related to functional modifications.

  10. Olfactory bulb units - Activity correlated with inhalation cycles and odor quality.

    NASA Technical Reports Server (NTRS)

    Macrides, F.; Chorover, S. L.

    1972-01-01

    Single olfactory bulb units were studied in two macrosmatic species of rodents under conditions intended to preserve the cyclical stimulation which normally accompanies nasal breathing. Patterns of unit activity related to the inhalation cycle were observed in all animals, often in the absence of specific stimuli, and could not be explained in simple mechanical terms. Distinctive changes in these patterns occurred in response to certain odors, and were generally independent of changes in the overall firing frequency. These findings indicate that a change in the overall firing frequency of unit discharges is neither a necessary nor sufficient measure of responsiveness to odors in the rodent olfactory bulb, and that stimulus-specific temporal distributions of unit firing may be involved in olfacto-endocrine activities.

  11. Invasive sinonasal adenocarcinoma with an absent olfactory bulb: a case report.

    PubMed

    Newman, Thomas H; Tipper, Geoffrey A; Hussain, Zakier

    2016-01-01

    Sinonasal adenocarcinomas are rare, locally invasive tumours. In this case the symptomatic profile was unusual and the diagnosis was missed at the primary care stage. Interestingly this would be the first documented case with an absent ipsilateral olfactory bulb. A 55-year old male presented with symptoms of behavioural change and mild headaches. He was later found to have a large Sinonasal adenocarcinoma which penetrated the skull base. This was treated by a combined craniotomy and endonasal approach. Sinonasal adenocarcinomas are unusual tumours and further research is required in order to clarify management strategies and prognosis. This interesting case was more unusual again given its presentation, extent and absence of the olfactory bulb. Importantly for primary care physicians the initial diagnosis was considered psychiatric rather than organic; despite there being specific features of the presentation which were suggestive of an intra-cranial lesion. PMID:27402540

  12. Calcium permeable AMPA receptors and autoreceptors in external tufted cells of rat olfactory bulb

    PubMed Central

    Ma, Jie; Lowe, Graeme

    2007-01-01

    Glomeruli are functional units of the olfactory bulb responsible for early processing of odor information encoded by single olfactory receptor genes. Glomerular neural circuitry includes numerous external tufted (ET) cells whose rhythmic burst firing may mediate synchronization of bulbar activity with the inhalation cycle. Bursting is entrained by glutamatergic input from olfactory nerve terminals, so specific properties of ionotropic glutamate receptors on ET cells are likely to be important determinants of olfactory processing. Particularly intriguing is recent evidence that α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors of juxta-glomerular neurons may permeate calcium. This could provide a novel pathway for regulating ET cell signaling. We tested the hypothesis that ET cells express functional calcium-permeable AMPA receptors. In rat olfactory bulb slices, excitatory postsynaptic currents (EPSCs) in ET cells were evoked by olfactory nerve shock, and by uncaging glutamate. We found attenuation of AMPA/kainate EPSCs by 1-naphthyl acetyl-spermine (NAS), an open-channel blocker specific for calcium permeable AMPA receptors. Cyclothiazide strongly potentiated EPSCs, indicating a major contribution from AMPA receptors. The current-voltage (I-V) relation of uncaging EPSCs showed weak inward rectification which was lost after > ~ 10 min of whole-cell dialysis, and was absent in NAS. In kainate-stimulated slices, Co2+ ions permeated cells of the glomerular layer. Large AMPA EPSCs were accompanied by fluorescence signals in fluo-4 loaded cells, suggesting calcium permeation. Depolarizing pulses evoked slow tail currents with pharmacology consistent with involvement of calcium permeable AMPA autoreceptors. Tail currents were abolished by Cd2+ and NBQX, and were sensitive to NAS block. Glutamate autoreceptors were confirmed by uncaging intracellular calcium to evoke a large inward current. Our results provide evidence that calcium permeable AMPA

  13. Rapid Feedforward Inhibition and Asynchronous Excitation Regulate Granule Cell Activity in the Mammalian Main Olfactory Bulb

    PubMed Central

    Burton, Shawn D.

    2015-01-01

    Granule cell-mediated inhibition is critical to patterning principal neuron activity in the olfactory bulb, and perturbation of synaptic input to granule cells significantly alters olfactory-guided behavior. Despite the critical role of granule cells in olfaction, little is known about how sensory input recruits granule cells. Here, we combined whole-cell patch-clamp electrophysiology in acute mouse olfactory bulb slices with biophysical multicompartmental modeling to investigate the synaptic basis of granule cell recruitment. Physiological activation of sensory afferents within single glomeruli evoked diverse modes of granule cell activity, including subthreshold depolarization, spikelets, and suprathreshold responses with widely distributed spike latencies. The generation of these diverse activity modes depended, in part, on the asynchronous time course of synaptic excitation onto granule cells, which lasted several hundred milliseconds. In addition to asynchronous excitation, each granule cell also received synchronous feedforward inhibition. This inhibition targeted both proximal somatodendritic and distal apical dendritic domains of granule cells, was reliably recruited across sniff rhythms, and scaled in strength with excitation as more glomeruli were activated. Feedforward inhibition onto granule cells originated from deep short-axon cells, which responded to glomerular activation with highly reliable, short-latency firing consistent with tufted cell-mediated excitation. Simulations showed that feedforward inhibition interacts with asynchronous excitation to broaden granule cell spike latency distributions and significantly attenuates granule cell depolarization within local subcellular compartments. Collectively, our results thus identify feedforward inhibition onto granule cells as a core feature of olfactory bulb circuitry and establish asynchronous excitation and feedforward inhibition as critical regulators of granule cell activity. SIGNIFICANCE

  14. Sexual Dimorphism in the Human Olfactory Bulb: Females Have More Neurons and Glial Cells than Males

    PubMed Central

    Oliveira-Pinto, Ana V.; Santos, Raquel M.; Coutinho, Renan A.; Oliveira, Lays M.; Santos, Gláucia B.; Alho, Ana T. L.; Leite, Renata E. P.; Farfel, José M.; Suemoto, Claudia K.; Grinberg, Lea T.; Pasqualucci, Carlos A.; Jacob-Filho, Wilson; Lent, Roberto

    2014-01-01

    Sex differences in the human olfactory function reportedly exist for olfactory sensitivity, odorant identification and memory, and tasks in which odors are rated based on psychological features such as familiarity, intensity, pleasantness, and others. Which might be the neural bases for these behavioral differences? The number of cells in olfactory regions, and especially the number of neurons, may represent a more accurate indicator of the neural machinery than volume or weight, but besides gross volume measures of the human olfactory bulb, no systematic study of sex differences in the absolute number of cells has yet been undertaken. In this work, we investigate a possible sexual dimorphism in the olfactory bulb, by quantifying postmortem material from 7 men and 11 women (ages 55–94 years) with the isotropic fractionator, an unbiased and accurate method to estimate absolute cell numbers in brain regions. Female bulbs weighed 0.132 g in average, while male bulbs weighed 0.137 g, a non-significant difference; however, the total number of cells was 16.2 million in females, and 9.2 million in males, a significant difference of 43.2%. The number of neurons in females reached 6.9 million, being no more than 3.5 million in males, a difference of 49.3%. The number of non-neuronal cells also proved higher in women than in men: 9.3 million and 5.7 million, respectively, a significant difference of 38.7%. The same differences remained when corrected for mass. Results demonstrate a sex-related difference in the absolute number of total, neuronal and non-neuronal cells, favoring women by 40–50%. It is conceivable that these differences in quantitative cellularity may have functional impact, albeit difficult to infer how exactly this would be, without knowing the specific circuits cells make. However, the reported advantage of women as compared to men may stimulate future work on sex dimorphism of synaptic microcircuitry in the olfactory bulb. PMID:25372872

  15. Segregated pathways to the vomeronasal amygdala: differential projections from the anterior and posterior divisions of the accessory olfactory bulb.

    PubMed

    Mohedano-Moriano, Alicia; Pro-Sistiaga, Palma; Ubeda-Bañón, Isabel; Crespo, Carlos; Insausti, Ricardo; Martinez-Marcos, Alino

    2007-04-01

    Apically and basally located receptor neurons in the vomeronasal sensory epithelium express G(i2 alpha)- and G(o alpha)-proteins, V1R and V2R vomeronasal receptors, project to the anterior and posterior accessory olfactory bulb and respond to different stimuli, respectively. The extent to which secondary projections from the two portions of the accessory olfactory bulb are convergent in the vomeronasal amygdala is controversial. This issue is addressed by using anterograde and retrograde tract-tracing methods in rats including electron microscopy. Injections of dextran-amines, Fluoro Gold, cholera toxin-B subunit and Fast Blue were delivered to the anterior and posterior accessory olfactory bulb, bed nucleus of the stria terminalis, dorsal anterior amygdala and bed nucleus of the accessory olfactory tract/anteroventral medial amygdaloid nucleus. We have demonstrated that, apart from common vomeronasal-recipient areas, only the anterior accessory olfactory bulb projects to the bed nucleus of the stria terminalis, medial division, posteromedial part, and only the posterior accessory olfactory bulb projects to the dorsal anterior amygdala and deep cell layers of the bed nucleus of the accessory olfactory tract and the anteroventral medial amygdaloid nucleus. These results provide evidence that, excluding areas of convergence, the V1R and V2R vomeronasal pathways project to specific areas of the amygdala. These two vomeronasal subsystems are therefore anatomically and functionally separated in the telencephalon.

  16. Sparse Distributed Representation of Odors in a Large-scale Olfactory Bulb Circuit

    PubMed Central

    Yu, Yuguo; McTavish, Thomas S.; Hines, Michael L.; Shepherd, Gordon M.; Valenti, Cesare; Migliore, Michele

    2013-01-01

    In the olfactory bulb, lateral inhibition mediated by granule cells has been suggested to modulate the timing of mitral cell firing, thereby shaping the representation of input odorants. Current experimental techniques, however, do not enable a clear study of how the mitral-granule cell network sculpts odor inputs to represent odor information spatially and temporally. To address this critical step in the neural basis of odor recognition, we built a biophysical network model of mitral and granule cells, corresponding to 1/100th of the real system in the rat, and used direct experimental imaging data of glomeruli activated by various odors. The model allows the systematic investigation and generation of testable hypotheses of the functional mechanisms underlying odor representation in the olfactory bulb circuit. Specifically, we demonstrate that lateral inhibition emerges within the olfactory bulb network through recurrent dendrodendritic synapses when constrained by a range of balanced excitatory and inhibitory conductances. We find that the spatio-temporal dynamics of lateral inhibition plays a critical role in building the glomerular-related cell clusters observed in experiments, through the modulation of synaptic weights during odor training. Lateral inhibition also mediates the development of sparse and synchronized spiking patterns of mitral cells related to odor inputs within the network, with the frequency of these synchronized spiking patterns also modulated by the sniff cycle. PMID:23555237

  17. Glucose sensitivity of mouse olfactory bulb neurons is conveyed by a voltage-gated potassium channel

    PubMed Central

    Tucker, Kristal; Cho, Sukhee; Thiebaud, Nicolas; Henderson, Michael X; Fadool, Debra Ann

    2013-01-01

    The olfactory bulb has recently been proposed to serve as a metabolic sensor of internal chemistry, particularly that modified by metabolism. Because the voltage-dependent potassium channel Kv1.3 regulates a large proportion of the outward current in olfactory bulb neurons and gene-targeted deletion of the protein produces a phenotype of resistance to diet-induced obesity in mice, we hypothesized that this channel may play a role in translating energy availability into a metabolic signal. Here we explored the ability of extracellular glucose concentration to modify evoked excitability of the mitral neurons that principally regulate olfactory coding and processing of olfactory information. Using voltage-clamp electrophysiology of heterologously expressed Kv1.3 channels in HEK 293 cells, we found that Kv1.3 macroscopic currents responded to metabolically active (d-) rather than inactive (l-) glucose with a response profile that followed a bell-shaped curve. Olfactory bulb slices stimulated with varying glucose concentrations showed glucose-dependent mitral cell excitability as evaluated by current-clamp electrophysiology. While glucose could be either excitatory or inhibitory, the majority of the sampled neurons displayed a decreased firing frequency in response to elevated glucose concentration that was linked to increased latency to first spike and decreased action potential cluster length. Unlike modulation attributed to phosphorylation, glucose modulation of mitral cells was rapid, less than one minute, and was reversible within the time course of a patch recording. Moreover, we report that modulation targets properties of spike firing rather than action potential shape, involves synaptic activity of glutamate or GABA signalling circuits, and is dependent upon Kv1.3 expression. Given the rising incidence of metabolic disorders attributed to weight gain, changes in neuronal excitability in brain regions regulating sensory perception of food are of consequence

  18. Persistent anosmia and olfactory bulb atrophy after mulga (Pseudechis australis) snakebite.

    PubMed

    Sethi, Moksh; Cook, Mark; Winkel, Kenneth D

    2016-07-01

    Loss of sense of smell is an intriguing yet under-recognised complication of snakebite. We report olfactory function testing and neuroimaging of the olfactory bulbs in a 30-year-old man with anosmia persisting for more than 1year after mulga (Pseudechis australis) snakebite. This problem was first noted by the patient 1week after being definitely bitten in Queensland, Australia. He had then presented to a regional hospital where his envenomation was considered mild enough to not warrant antivenom administration. A week later the patient noted a reduction of sense of smell, which progressed to complete inability to smell over the ensuing weeks. On clinical review the patient's neurologic and rhinologic examination did not reveal any structural cause for anosmia. Formal olfactory testing was performed using ''sniffin' sticks" and the patient scored 17 on this test, indicating severe hyposmia (functional anosmia <16.5, normal score >30.3 for men aged 16-35years). MRI of the brain showed no abnormalities. The olfactory bulb volumes were then measured on a volumetric T2-weighted MRI that demonstrated significantly reduced volume of both bulbs, with the right 34.86mm(3) and left 36.25mm(3) (normal volume ⩾58mm(3), 10th centile). The current patient represents a rare instance of a definite, untreated, elapid (mulga snake) envenomation with an intriguing disjunction between the mildness of the systemic features and the severity of the olfactory lesion. It is also unclear if early antivenom use attenuates this condition, and due to the delayed manifestation of the symptoms, awareness of this phenomenon may be lacking amongst physicians. PMID:26896910

  19. Improved spatial accuracy of functional maps in the rat olfactory bulb using supervised machine learning approach.

    PubMed

    Murphy, Matthew C; Poplawsky, Alexander J; Vazquez, Alberto L; Chan, Kevin C; Kim, Seong-Gi; Fukuda, Mitsuhiro

    2016-08-15

    Functional MRI (fMRI) is a popular and important tool for noninvasive mapping of neural activity. As fMRI measures the hemodynamic response, the resulting activation maps do not perfectly reflect the underlying neural activity. The purpose of this work was to design a data-driven model to improve the spatial accuracy of fMRI maps in the rat olfactory bulb. This system is an ideal choice for this investigation since the bulb circuit is well characterized, allowing for an accurate definition of activity patterns in order to train the model. We generated models for both cerebral blood volume weighted (CBVw) and blood oxygen level dependent (BOLD) fMRI data. The results indicate that the spatial accuracy of the activation maps is either significantly improved or at worst not significantly different when using the learned models compared to a conventional general linear model approach, particularly for BOLD images and activity patterns involving deep layers of the bulb. Furthermore, the activation maps computed by CBVw and BOLD data show increased agreement when using the learned models, lending more confidence to their accuracy. The models presented here could have an immediate impact on studies of the olfactory bulb, but perhaps more importantly, demonstrate the potential for similar flexible, data-driven models to improve the quality of activation maps calculated using fMRI data. PMID:27236085

  20. Effects of in utero odorant exposure on neuroanatomical development of the olfactory bulb and odour preferences

    PubMed Central

    Todrank, Josephine; Heth, Giora; Restrepo, Diego

    2011-01-01

    Human babies and other young mammals prefer food odours and flavours of their mother's diet during pregnancy as well as their mother's individually distinctive odour. Newborn mice also prefer the individual odours of more closely related—even unfamiliar—lactating females. If exposure to in utero odorants—which include metabolites from the mother's diet and the foetus's genetically determined individual odour—helps shape the neuroanatomical development of the olfactory bulb, this could influence the perception of such biologically important odours that are preferred after birth. We exposed gene-targeted mice during gestation and nursing to odorants that activate GFP-tagged olfactory receptors (ORs) and then measured the effects on the size of tagged glomeruli in the olfactory bulb where axons from olfactory sensory neurons (OSNs) coalesce by OR type. We found significantly larger tagged glomeruli in mice exposed to these activating odorants in amniotic fluid, and later in mother's milk, as well as significant preferences for the activating odour. Larger glomeruli comprising OSNs that respond to consistently encountered odorants should enhance detection and discrimination of these subsequently preferred odours, which in nature would facilitate selection of palatable foods and kin recognition, through similarities in individual odours of relatives. PMID:21123261

  1. Odor Information Processing by the Olfactory Bulb Analyzed in Gene-Targeted Mice

    PubMed Central

    Tan, Jie; Savigner, Agnès; Ma, Minghong; Luo, Minmin

    2010-01-01

    SUMMARY In mammals, olfactory sensory neurons (OSNs) expressing a specific odorant receptor (OR) gene project with precise stereotypy onto mitral/tufted (M/T) cells in the main olfactory bulb (MOB). It remains challenging to understand how incoming olfactory signals are transformed into outputs of M/T cells. By recording from OSNs expressing mouse I7 receptor and their postsynaptic neurons in the bulb, we found that I7 OSNs and their corresponding M/T cells exhibit similarly selective tuning profiles at low concentrations. Increasing the concentration significantly reduces response selectivity for both OSNs and M/T cells, although the tuning curve of M/T cells remains comparatively narrow. By contrast, interneurons in the MOB are broadly tuned, and blocking GABAergic neurotransmission reduces selectivity of M/T cells at high odorant concentrations. Our results indicate that olfactory information carried by an OR is channeled to its corresponding M/T cells and support the role of lateral inhibition via interneurons in sharpening the tuning of M/T cells. PMID:20346765

  2. Neuronal pattern separation in the olfactory bulb improves odor discrimination learning

    PubMed Central

    Lagier, Samuel; Begnaud, Frédéric; Rodriguez, Ivan; Carleton, Alan

    2015-01-01

    Neuronal pattern separation is thought to enable the brain to disambiguate sensory stimuli with overlapping features thereby extracting valuable information. In the olfactory system, it remains unknown whether pattern separation acts as a driving force for sensory discrimination and the learning thereof. Here we show that overlapping odor-evoked input patterns to the mouse olfactory bulb (OB) are dynamically reformatted in the network at the timescale of a single breath, giving rise to separated patterns of activity in ensemble of output neurons (mitral/tufted cells; M/T). Strikingly, the extent of pattern separation in M/T assemblies predicts behavioral discrimination performance during the learning phase. Furthermore, exciting or inhibiting GABAergic OB interneurons, using optogenetics or pharmacogenetics, altered pattern separation and thereby odor discrimination learning in a bidirectional way. In conclusion, we propose that the OB network can act as a pattern separator facilitating olfactory stimuli distinction, a process that is sculpted by synaptic inhibition. PMID:26301325

  3. Experience-dependent modification of primary sensory synapses in the mammalian olfactory bulb.

    PubMed

    Tyler, William J; Petzold, Gabor C; Pal, Sumon K; Murthy, Venkatesh N

    2007-08-29

    Experience-dependent changes in neural circuits have traditionally been investigated several synapses downstream of sensory input. Whether experience can alter the strength of primary sensory synapses remains mostly unknown. To address this issue, we investigated the consequences of odor deprivation on synapses made by olfactory sensory axons in the olfactory bulb of rats. Odor deprivation triggered an increase in the probability of glutamate release from olfactory sensory neuron synapses. Deprivation also increased the amplitude of quantal synaptic currents mediated by AMPA- and NMDA-type glutamate receptors, as well as the abundance of these receptors in the glomerular region. Our results demonstrate that sensory experience is capable of modulating synaptic strength at the earliest stages of information transfer between the environment and an organism. Such compensatory experience-dependent changes may represent a mechanism of sensory gain control.

  4. Comprehensive connectivity of the mouse main olfactory bulb: analysis and online digital atlas

    PubMed Central

    Hintiryan, Houri; Gou, Lin; Zingg, Brian; Yamashita, Seita; Lyden, Hannah M.; Song, Monica Y.; Grewal, Arleen K.; Zhang, Xinhai; Toga, Arthur W.; Dong, Hong-Wei

    2012-01-01

    We introduce the first open resource for mouse olfactory connectivity data produced as part of the Mouse Connectome Project (MCP) at UCLA. The MCP aims to assemble a whole-brain connectivity atlas for the C57Bl/6J mouse using a double coinjection tracing method. Each coinjection consists of one anterograde and one retrograde tracer, which affords the advantage of simultaneously identifying efferent and afferent pathways and directly identifying reciprocal connectivity of injection sites. The systematic application of double coinjections potentially reveals interaction stations between injections and allows for the study of connectivity at the network level. To facilitate use of the data, raw images are made publicly accessible through our online interactive visualization tool, the iConnectome, where users can view and annotate the high-resolution, multi-fluorescent connectivity data (www.MouseConnectome.org). Systematic double coinjections were made into different regions of the main olfactory bulb (MOB) and data from 18 MOB cases (~72 pathways; 36 efferent/36 afferent) currently are available to view in iConnectome within their corresponding atlas level and their own bright-field cytoarchitectural background. Additional MOB injections and injections of the accessory olfactory bulb (AOB), anterior olfactory nucleus (AON), and other olfactory cortical areas gradually will be made available. Analysis of connections from different regions of the MOB revealed a novel, topographically arranged MOB projection roadmap, demonstrated disparate MOB connectivity with anterior versus posterior piriform cortical area (PIR), and exposed some novel aspects of well-established cortical olfactory projections. PMID:22891053

  5. [Oxidative metabolism of main and accessory olfactory bulbs, limpic system and hypothalamus during the estral cycle of the rat (author's transl)].

    PubMed

    Sánchez-Criado, J E

    1979-06-01

    The in vitro oxidative metabolism of hypothalamus, olfactory and limbic systems from female rats in the estrous cycle have been measured. The accessory olfactory bulb becomes most active during diestrous when the hypothalamus reaches its lowest values.

  6. Vasoactive intestinal polypeptide mediates circadian rhythms in mammalian olfactory bulb and olfaction.

    PubMed

    Miller, Jae-Eun Kang; Granados-Fuentes, Daniel; Wang, Thomas; Marpegan, Luciano; Holy, Timothy E; Herzog, Erik D

    2014-04-23

    Accumulating evidence suggests that the olfactory bulbs (OBs) function as an independent circadian system regulating daily rhythms in olfactory performance. However, the cells and signals in the olfactory system that generate and coordinate these circadian rhythms are unknown. Using real-time imaging of gene expression, we found that the isolated olfactory epithelium and OB, but not the piriform cortex, express similar, sustained circadian rhythms in PERIOD2 (PER2). In vivo, PER2 expression in the OB of mice is circadian, approximately doubling with a peak around subjective dusk. Furthermore, mice exhibit circadian rhythms in odor detection performance with a peak at approximately subjective dusk. We also found that circadian rhythms in gene expression and odor detection performance require vasoactive intestinal polypeptide (VIP) or its receptor VPAC2R. VIP is expressed, in a circadian manner, in interneurons in the external plexiform and periglomerular layers, whereas VPAC2R is expressed in mitral and external tufted cells in the OB. Together, these results indicate that VIP signaling modulates the output from the OB to maintain circadian rhythms in the mammalian olfactory system.

  7. Basal telencephalic regions connected with the olfactory bulb in a Madagascan hedgehog tenrec.

    PubMed

    Künzle, H; Radtke-Schuller, S

    2000-08-01

    In an attempt to gain insight into the organization and evolution of the basal forebrain, the region was analysed cytoarchitecturally, chemoarchitecturally, and hodologically in a lower placental mammal, the lesser hedgehog tenrec. Particular emphasis was laid on the subdivision of the olfactory tubercle, the nuclear complex of the diagonal band, and the cortical amygdala. The proper tubercule and the rostrolateral tubercular seam differed from each other with regard to their immunoreactivity to calbindin and calretinin, as well as their afferents from the piriform cortex. Interestingly, the tubercular seam showed similar properties to the dwarf cell compartment, located immediately adjacent to the islands of Calleja. The most prominent input to the olfactory bulb (OfB) originated from the diagonal nuclear complex. This projection was ipsilateral, whereas the bulbar afferents from the hypothalamus and the mesopontine tegmentum were bilateral. The amygdala projected only sparsely to the OfB, but received a prominent bulbar projection. An exception was the nucleus of the lateral olfactory tract, which was poorly connected with the OfB. Unlike other species with an accessory OfB, the projections from the tenrec's main OfB did not show a topographic organization upon the lateral and medial olfactory amygdala. However, there was an accessory amygdala, which could be differentiated from the lateral nuclei by its intense reaction to NADPh-diaphorase. This reaction was poor in the diagonal nuclear complex as in monkey but unlike in rat. The variability of cell populations and olfactory bulb connections shown here may help to clarify both phylogenetic relationships and the significance of individual basal telencephalic subdivisions.

  8. Impact of apoE deficiency during synaptic remodeling in the mouse olfactory bulb

    PubMed Central

    Nwosu, Ikemefuna; Gairhe, Salina; Struble, Robert G.; Nathan, Britto P.

    2008-01-01

    In this study we examined the role of apoE on the rate of synaptic recovery in the olfactory bulb (OB) following olfactory epithelium (OE) lesioning in mice. We used both immunoblotting and immunohistochemical techniques to compare the density of OB synaptophysin (Syn, a synaptic marker) in apoE-gene deficient/knockout (KO) mice and wild-type (WT) mice following OE lesion. We found that the whole bulb concentrations of Syn, measured by immunoblotting, declined sharply following injury in both WT and KO mice during the degenerative phase (3–7 days). After this initial decline, the Syn concentration gradually increased to normal levels by 56 days in WT mice. In contrast, Syn concentration in KO mice did not recover by day 56 when Syn density in WT was essentially normal. Glomerular Syn density, measured by immunohistochemistry, found a lower density in KO mice at all time points post lesion. This lower concentration of whole bulb Syn parallels the slower recovery of glomerular area in KO mice. The data indicate that apoE deficiency in KO mice is associated with a delayed recovery of the glomerular area and a slower recovery in Syn concentration in the OB. PMID:18621483

  9. Nonlinear dynamics of pattern formation and pattern recognition in the rabbit olfactory bulb

    NASA Astrophysics Data System (ADS)

    Baird, Bill

    1986-10-01

    A mathematical model of the process of pattern recognition in the first olfactory sensory cortex of the rabbit is presented. It explains the formation and alteration of spatial patterns in neural activity observed experimentally during classical Pavlovian conditioning. On each inspiration of the animal, a surge of receptor input enters the olfactory bulb. EEG activity recorded at the surface of the bulb undergoes a transition from a low amplitude background state of temporal disorder to coherent oscillation. There is a distinctive spatial pattern of rms amplitude in this oscillation which changes reliably to a second pattern during each successful recognition by the animal of a conditioned stimulus odor. When a new odor is paired as conditioned stimulus, these patterns are replaced by new patterns that stabilize as the animal adapts to the new environment. I will argue that a unification of the theories of pattern formation and associative memory is required to account for these observations. This is achieved in a model of the bulb as a discrete excitable medium with spatially inhomogeneous coupling expressed by a connection matrix. The theory of multiple Hopf bifurcations is employed to find coupled equations for the amplitudes of competing unstable oscillatory modes. These may be created in the system by proper coupling and selectively evoked by specific classes of inputs. This allows a view of limit cycle attractors as “stored” fixed points of a gradient vector field and thereby recovers the more familiar dynamical systems picture of associative memory.

  10. Stressors impair odor recognition memory via an olfactory bulb-dependent noradrenergic mechanism

    PubMed Central

    Manella, Laura C.; Alperin, Samuel; Linster, Christiane

    2013-01-01

    Non-associative habituation and odor recognition tasks have been widely used to probe questions of social recognition, odor memory duration, and odor memory specificity. Among others, these paradigms have provided valuable insight into how neuromodulation, and specifically norepinephrine/noradrenaline (NE) influences odor memory. In general, NE levels are modulated by arousal, stress, and behavioral state, but there is sparse evidence of a direct relationship between NE and odor memory in adult rodents. The present study uses simple mild psychological stressors (bright light and sound) to modulate NE levels physiologically in order to probe stressors NE-dependent effect on odor recognition memory. In rats with bilateral bulbar cannulations, we show that these stressors modulate olfactory memory and that this effect is at least partially mediated by the olfactory bulb. Specifically, we show that the presence of stressors during the acquisition of odor memory suppresses memory for an odor when tested 30 min after familiarization to that odor. This suppression is blocked by infusing NE antagonists into the olfactory bulb prior to odor acquisition. Additionally, we find that infusion of bulbar NE is sufficient to suppress odor memory in a manner mimicking that of our stressors. These effects are unlikely to be solely mediated by locomotor/exploratory changes produced by stressors, although these stressors influence certain behaviors not directly related to odor investigation. This study provides important information about how behaviorally relevant changes in NE can influence top-down sensory processing and odor memory. PMID:24391558

  11. Exposure to Sevoflurane Affects the Development of Parvalbumin Interneurons in the Main Olfactory Bulb in Mice

    PubMed Central

    Yang, Jing; Chen, Jing; Cai, Guohong; Lu, Rui; Sun, Tingting; Luo, Tingting; Wu, Shengxi; Ling, Shucai

    2016-01-01

    Sevoflurane is widely used in adult and pediatric patients during clinical surgeries. Although studies have shown that exposure to sevoflurane impairs solfactory memory after an operation, the neuropathological changes underlying this effect are not clear. This study detected the effect of sevoflurane exposure on the development of calcium-binding proteins-expressing interneurons in the main olfactory bulb (MOB). We exposed neonatal mice to 2% sevoflurane at two different developmental time points and found that exposing mice to sevoflurane at postnatal day (PD) 7 significantly decreased the expression of GAD67 and parvalbumin (PV) in the olfactory bulb (OB) but did not alter the expression of calretinin (CR) or calbindin D28k (CB). The number and dendritic morphology of PV-expressing interneurons in the MOB were impaired by exposure to sevoflurane at PD7. However, exposure to sevoflurane at PD10 had no effect on calcium-binding protein expression or the number and dendritic morphology of PV-expressing interneurons in the MOB. These results suggest that exposing neonatal mice to sevoflurane during a critical period of olfactory development affects the development of PV-expressing interneurons in the MOB. PMID:27445710

  12. Olfactory Bulb Field Potentials and Respiration in Sleep-Wake States of Mice.

    PubMed

    Jessberger, Jakob; Zhong, Weiwei; Brankačk, Jurij; Draguhn, Andreas

    2016-01-01

    It is well established that local field potentials (LFP) in the rodent olfactory bulb (OB) follow respiration. This respiration-related rhythm (RR) in OB depends on nasal air flow, indicating that it is conveyed by sensory inputs from the nasal epithelium. Recently RR was found outside the olfactory system, suggesting that it plays a role in organizing distributed network activity. It is therefore important to measure RR and to delineate it from endogenous electrical rhythms like theta which cover similar frequency bands in small rodents. In order to validate such measurements in freely behaving mice, we compared rhythmic LFP in the OB with two respiration-related biophysical parameters: whole-body plethysmography (PG) and nasal temperature (thermocouple; TC). During waking, all three signals reflected respiration with similar reliability. Peak power of RR in OB decreased with increasing respiration rate whereas power of PG increased. During NREM sleep, respiration-related TC signals disappeared and large amplitude slow waves frequently concealed RR in OB. In this situation, PG provided a reliable signal while breathing-related rhythms in TC and OB returned only during microarousals. In summary, local field potentials in the olfactory bulb do reliably reflect respiratory rhythm during wakefulness and REM sleep but not during NREM sleep. PMID:27247803

  13. Reduced nasal transport of insulin-like growth factor-1 to the mouse cerebrum with olfactory bulb resection.

    PubMed

    Shiga, Hideaki; Nagaoka, Mikiya; Washiyama, Kohshin; Yamamoto, Junpei; Yamada, Kentaro; Noda, Takuya; Harita, Masayuki; Amano, Ryohei; Miwa, Takaki

    2014-09-01

    Although the olfactory nerve is involved in nasal transport of insulin-like growth factor-1 (IGF-1) to the brain, to our knowledge there have been no direct assessments of the effects of olfactory nerve damage on this transport. To determine whether olfactory bulb resection resulted in reduced transport of nasally administered human recombinant IGF-1 (hIGF-1) to the cerebrum, we measured the uptake of nasally administered iodine-125 hIGF-1 ((125)I-hIGF-1) in the cerebrum as a percentage of that in the blood in male ICR mice subjected to left olfactory bulb resection (model mice) and in sham-operated male ICR mice (control mice). Phosphorylated extracellular signal-regulated kinase (ERK) 1/2 (Thr202/Tyr204)/(Thr185/Tyr187) as a percentage of total ERK 1/2 in the left cerebrum was also assessed by using enzyme-linked immunosorbent assay after nasal administration of hIGF-1. Uptake of nasally administered (125)I-hIGF-1 in the cerebrum as a percentage of that in the blood was significantly lower in the model group than in the control group 30min after nasal administration of hIGF-1. Unilateral olfactory bulb resection prevented nasally administered hIGF-1 from increasing the phosphorylation of ERK 1/2 in the mouse cerebrum in vivo. These findings suggest that olfactory bulb damage reduces nasal transport of hIGF-1 to the brain in vivo.

  14. Increase of peripheral type benzodiazepine binding sites in kidney and olfactory bulb in acutely stressed rats.

    PubMed

    Novas, M L; Medina, J H; Calvo, D; De Robertis, E

    1987-03-17

    Fifteen minutes after the initiation of swimming stress in the rat we observed a 50% increase in the number of [3H]RO 5-4864 binding sites in kidney and a 37% increase in the olfactory bulb, without change in affinity. The binding in heart and cerebral cortex remained unchanged after the stress. These results are discussed in relation to previous work on both the action of an acute stress in central benzodiazepine receptors and the possible modulation of peripheral benzodiazepine receptors of the kidney by adrenocortical hormones.

  15. Sensory-Evoked Intrinsic Imaging Signals in the Olfactory Bulb Are Independent of Neurovascular Coupling

    PubMed Central

    Vincis, Roberto; Lagier, Samuel; Van De Ville, Dimitri; Rodriguez, Ivan; Carleton, Alan

    2016-01-01

    Summary Functional brain-imaging techniques used in humans and animals, such as functional MRI and intrinsic optical signal (IOS) imaging, are thought to largely rely on neurovascular coupling and hemodynamic responses. Here, taking advantage of the well-described micro-architecture of the mouse olfactory bulb, we dissected the nature of odor-evoked IOSs. Using in vivo pharmacology in transgenic mouse lines reporting activity in different cell types, we show that parenchymal IOSs are largely independent of neurotransmitter release and neurovascular coupling. Furthermore, our results suggest that odor-evoked parenchymal IOSs originate from changes in light scattering of olfactory sensory neuron axons, mostly due to water movement following action potential propagation. Our study sheds light on a direct correlate of neuronal activity, which may be used for large-scale functional brain imaging. PMID:26146075

  16. Adult Born Olfactory Bulb Dopaminergic Interneurons: Molecular Determinants and Experience-Dependent Plasticity

    PubMed Central

    Bonzano, Sara; Bovetti, Serena; Gendusa, Claudio; Peretto, Paolo; De Marchis, Silvia

    2016-01-01

    The olfactory bulb (OB) is a highly plastic brain region involved in the early processing of olfactory information. A remarkably feature of the OB circuits in rodents is the constitutive integration of new neurons that takes place during adulthood. Newborn cells in the adult OB are mostly inhibitory interneurons belonging to chemically, morphologically and functionally heterogeneous types. Although there is general agreement that adult neurogenesis in the OB plays a key role in sensory information processing and olfaction-related plasticity, the contribution of each interneuron subtype to such functions is far to be elucidated. Here, we focus on the dopaminergic (DA) interneurons: we highlight recent findings about their morphological features and then describe the molecular factors required for the specification/differentiation and maintenance of the DA phenotype in adult born neurons. We also discuss dynamic changes of the DA interneuron population related to age, environmental stimuli and lesions, and their possible functional implications. PMID:27199651

  17. Reduction of the number of new cells reaching olfactory bulbs impairs olfactory perception in the adult opossum.

    PubMed

    Grabiec, Marta; Turlejski, Kris; Djavadian, Rouzanna

    2009-01-01

    In adult mammals cells generated in the subventricular zone (SVZ) migrate to olfactory bulbs (OB). Functional significance of this continuous neurogenesis is not clear. We injected opossums (Monodelphis domestica) for seven consecutive days with a 5HT(1A) agonist (8-OH-DPAT or buspirone) or its antagonist WAY100635. One hour after each of these injections bromodeoxyuridine (BrdU) a marker of dividing cells was also injected. Two months later, when newly generated neurons settled in the OB and matured the ability of these opossums to detect hidden food by olfactory cues was tested. Afterwards, numbers of BrdU-labeled cell nuclei in their OB were counted and a phenotype of labeled cells established. In all groups investigated the majority of new cells differentiated into neurons (55-76%) and a lower proportion into astroglia (6-12%). Numbers of BrdU-labeled cells differed depending on the applied treatment: both agonists of the 5HT(1A) receptor increased these numbers, while its antagonist decreased them. The increased number of new OB interneurons did not change the time required for finding all three food items and therefore did not improve the opossums' performance in this test of the olfactory perception. However, opossums that had the reduced number of new generated OB cells searched longer for each food item and in consequence took three times longer to find all three crickets, than did opossums from other groups. In conclusion, lower numbers of new neurons in the opossums OB correlated with their worse behavioral performance in a test based on olfactory perception.

  18. Not all sharks are "swimming noses": variation in olfactory bulb size in cartilaginous fishes.

    PubMed

    Yopak, Kara E; Lisney, Thomas J; Collin, Shaun P

    2015-03-01

    Olfaction is a universal modality by which all animals sample chemical stimuli from their environment. In cartilaginous fishes, olfaction is critical for various survival tasks including localizing prey, avoiding predators, and chemosensory communication with conspecifics. Little is known, however, about interspecific variation in olfactory capability in these fishes, or whether the relative importance of olfaction in relation to other sensory systems varies with regard to ecological factors, such as habitat and lifestyle. In this study, we have addressed these questions by directly examining interspecific variation in the size of the olfactory bulbs (OB), the region of the brain that receives the primary sensory projections from the olfactory nerve, in 58 species of cartilaginous fishes. Relative OB size was compared among species occupying different ecological niches. Our results show that the OBs maintain a substantial level of allometric independence from the rest of the brain across cartilaginous fishes and that OB size is highly variable among species. These findings are supported by phylogenetic generalized least-squares models, which show that this variability is correlated with ecological niche, particularly habitat. The relatively largest OBs were found in pelagic-coastal/oceanic sharks, especially migratory species such as Carcharodon carcharias and Galeocerdo cuvier. Deep-sea species also possess large OBs, suggesting a greater reliance on olfaction in habitats where vision may be compromised. In contrast, the smallest OBs were found in the majority of reef-associated species, including sharks from the families Carcharhinidae and Hemiscyllidae and dasyatid batoids. These results suggest that there is great variability in the degree to which these fishes rely on olfactory cues. The OBs have been widely used as a neuroanatomical proxy for olfactory capability in vertebrates, and we speculate that differences in olfactory capabilities may be the result of

  19. Two types of periglomerular cells in the olfactory bulb of the macaque monkey (Macaca fascicularis).

    PubMed

    Liberia, Teresa; Blasco-Ibáñez, José Miguel; Nácher, Juan; Varea, Emilio; Lanciego, José Luis; Crespo, Carlos

    2013-07-01

    The olfactory bulb (OB) of mammals is the brain region that receives the sensory information coming from the olfactory epithelium. The entrance of the olfactory information occurs in spherical structures of neuropil named olfactory glomeruli and is modulated by a population of interneurons known as periglomerular cells (PG). It has been demonstrated that there are two types of PG in the OB of some macrosmatic mammals, including rats and mice. Type 1 PG (PG-1) receive synapses from the olfactory nerve, whereas type 2 PG (PG-2) do not receive synapses from the olfactory axons. To date, the presence of the two types of PG has not been investigated in microsmatic mammals. In this context, we analyze the presence of PG-1 and PG-2 in the OB of the long-tailed macaque (Macaca fascicularis). For that, we used the enzyme tyrosine hydroxylase, the neuronal isoform of the enzyme nitric oxide synthase and the calcium-binding proteins calbindin D-28k and calretinin as neurochemical markers. Our results demonstrate that the OB of the macaque contains PG-1 and PG-2. A subpopulation of PG-1 expresses tyrosine hydroxylase and another expresses the neuronal isoform of nitric oxide synthase. In addition, a subpopulation of PG-2 expresses calbindin D-28k and another expresses calretinin. Double immunofluorescence demonstrates that there is no colocalization of two markers in the same PG. These results mimic those found in macrosmatic animals. The presence of two types of PG in the glomerular circuits seems to be a key principle for the organization of the OB of mammals.

  20. Not all sharks are "swimming noses": variation in olfactory bulb size in cartilaginous fishes.

    PubMed

    Yopak, Kara E; Lisney, Thomas J; Collin, Shaun P

    2015-03-01

    Olfaction is a universal modality by which all animals sample chemical stimuli from their environment. In cartilaginous fishes, olfaction is critical for various survival tasks including localizing prey, avoiding predators, and chemosensory communication with conspecifics. Little is known, however, about interspecific variation in olfactory capability in these fishes, or whether the relative importance of olfaction in relation to other sensory systems varies with regard to ecological factors, such as habitat and lifestyle. In this study, we have addressed these questions by directly examining interspecific variation in the size of the olfactory bulbs (OB), the region of the brain that receives the primary sensory projections from the olfactory nerve, in 58 species of cartilaginous fishes. Relative OB size was compared among species occupying different ecological niches. Our results show that the OBs maintain a substantial level of allometric independence from the rest of the brain across cartilaginous fishes and that OB size is highly variable among species. These findings are supported by phylogenetic generalized least-squares models, which show that this variability is correlated with ecological niche, particularly habitat. The relatively largest OBs were found in pelagic-coastal/oceanic sharks, especially migratory species such as Carcharodon carcharias and Galeocerdo cuvier. Deep-sea species also possess large OBs, suggesting a greater reliance on olfaction in habitats where vision may be compromised. In contrast, the smallest OBs were found in the majority of reef-associated species, including sharks from the families Carcharhinidae and Hemiscyllidae and dasyatid batoids. These results suggest that there is great variability in the degree to which these fishes rely on olfactory cues. The OBs have been widely used as a neuroanatomical proxy for olfactory capability in vertebrates, and we speculate that differences in olfactory capabilities may be the result of

  1. The Effect of Chronic Methamphetamine Exposure on the Hippocampal and Olfactory Bulb Neuroproteomes of Rats

    PubMed Central

    Zhu, Rui; Yang, Tianjiao; Kobeissy, Firas; Mouhieddine, Tarek H.; Raad, Mohamad; Nokkari, Amaly; Gold, Mark S.; Wang, Kevin K.; Mechref, Yehia

    2016-01-01

    Nowadays, drug abuse and addiction are serious public health problems in the USA. Methamphetamine (METH) is one of the most abused drugs and is known to cause brain damage after repeated exposure. In this paper, we conducted a neuroproteomic study to evaluate METH-induced brain protein dynamics, following a two-week chronic regimen of an escalating dose of METH exposure. Proteins were extracted from rat brain hippocampal and olfactory bulb tissues and subjected to liquid chromatography-mass spectrometry (LC-MS/MS) analysis. Both shotgun and targeted proteomic analysis were performed. Protein quantification was initially based on comparing the spectral counts between METH exposed animals and their control counterparts. Quantitative differences were further confirmed through multiple reaction monitoring (MRM) LC-MS/MS experiments. According to the quantitative results, the expression of 18 proteins (11 in the hippocampus and 7 in the olfactory bulb) underwent a significant alteration as a result of exposing rats to METH. 13 of these proteins were up-regulated after METH exposure while 5 were down-regulated. The altered proteins belonging to different structural and functional families were involved in processes such as cell death, inflammation, oxidation, and apoptosis. PMID:27082425

  2. The Effect of Chronic Methamphetamine Exposure on the Hippocampal and Olfactory Bulb Neuroproteomes of Rats.

    PubMed

    Zhu, Rui; Yang, Tianjiao; Kobeissy, Firas; Mouhieddine, Tarek H; Raad, Mohamad; Nokkari, Amaly; Gold, Mark S; Wang, Kevin K; Mechref, Yehia

    2016-01-01

    Nowadays, drug abuse and addiction are serious public health problems in the USA. Methamphetamine (METH) is one of the most abused drugs and is known to cause brain damage after repeated exposure. In this paper, we conducted a neuroproteomic study to evaluate METH-induced brain protein dynamics, following a two-week chronic regimen of an escalating dose of METH exposure. Proteins were extracted from rat brain hippocampal and olfactory bulb tissues and subjected to liquid chromatography-mass spectrometry (LC-MS/MS) analysis. Both shotgun and targeted proteomic analysis were performed. Protein quantification was initially based on comparing the spectral counts between METH exposed animals and their control counterparts. Quantitative differences were further confirmed through multiple reaction monitoring (MRM) LC-MS/MS experiments. According to the quantitative results, the expression of 18 proteins (11 in the hippocampus and 7 in the olfactory bulb) underwent a significant alteration as a result of exposing rats to METH. 13 of these proteins were up-regulated after METH exposure while 5 were down-regulated. The altered proteins belonging to different structural and functional families were involved in processes such as cell death, inflammation, oxidation, and apoptosis. PMID:27082425

  3. Perinatal administration of diazepam alters sexual dimorphism in the rat accessory olfactory bulb.

    PubMed

    Pérez-Laso, C; Valencia, A; Rodríguez-Zafra, M; Calés, J M; Guillamón, A; Segovia, S

    1994-01-14

    The present study examines the effects of pre and/or early postnatal administration of diazepam on the mitral cell and on the light and dark granule cell populations in the sexually dimorphic accessory olfactory bulb of the rat. Quantitative differences related to sex were observed in the numbers of the three types of neurons, with vehicle males showing greater numbers of cells than vehicle females. The number of mitral cells in males decreased to the levels shown by female rats following prenatal and pre-postnatal diazepam treatments, whereas the DZ treatments did not affect the females. In addition, the diazepam administration during the prenatal, postnatal and pre-postnatal periods decreased the numbers of both light and dark granule cells in males, while these two granule cell subpopulations were not affected in diazepam treated females. These results indicate that perinatal administration of diazepam can alter the sexual dimorphism in the accessory olfactory bulb and that the GABAA/benzodiazepine receptor complex is involved in the sexual differentiation this part of the brain.

  4. A transient, RCK4-like K+ current in cultured Xenopus olfactory bulb neurons.

    PubMed

    Engel, J; Rabba, J; Schild, D

    1996-09-01

    A transient K+ current in cultured olfactory bulb neurons of Xenopus tadpoles was studied using the whole-cell patch-clamp technique. The current, which was resistant to 80 mM tetraethylammoniumchloride (TEA) and 10 nM charybdotoxin but blocked by 5 mM 4-aminopyridine (4-AP), activated between -60 and -40 mV and showed time- and voltage-dependent inactivation. Its peak amplitude was nearly independent of the extracellular K+ concentration ([K+]o) in the range of 0.05 to 10 mM, indicating that its conductance increased upon increasing [K+]o. The transient K+ current showed a slow recovery from inactivation with the time for half-maximum recovery from a conditioning pulse to 80 mV for 1 s varying from 100 ms to 500 ms. Complete recovery required as much as 5-10 s at -80 mV, but could be speeded up at hyperpolarized potentials. The current resembles the RCK4 (Kv1.4) current of rat neurons except that its recovery from inactivation was independent of [K+]o. High-frequency stimulation (20-67 Hz) of the neurons with short (5 ms) voltage pulses resulted in a frequency-dependent, progressive inactivation of the transient K+ current. This suggests that, during phasic responses of olfactory bulb neurons, inactivation of the transient K+ current occurs and may lead to lengthening of action potentials and facilitation of synaptic transmission.

  5. Short-term effects of endothelins on tyrosine hydroxylase activity and expression in the olfactory bulb of normotensive rats.

    PubMed

    Nabhen, Sabrina L; Perfume, Guadalupe; Battistone, María A; Rossi, Andrés; Abramoff, Tamara; Bianciotti, Liliana G; Vatta, Marcelo S

    2009-05-01

    The olfactory system in rats is part of the limbic region with extensive afferent connections with brain areas involved in the regulation of behaviour and autonomic responses. The existence of the endothelin system and catecholaminergic neurons in the olfactory bulb suggests that endothelins may modulate noradrenergic transmission and diverse olfactory mediated processes. In the present work we studied the effect of endothelin-1 and -3 on neuronal norepinephrine release and the short-term regulation of tyrosine hydroxylase in the olfactory bulb. Results showed that both endothelins increased tyrosine hydroxylase activity through the activation of a non-conventional endothelin G-protein coupled receptor, coupled to the stimulation of protein kinase A and C, as well as Ca(2+)/calmodulin-dependent protein kinase II. On the other hand, neither endothelin-1 nor endothelin-3 modified tyrosine hydroxylase total protein levels, but both peptides increased the phosphorylation of serine residues of the enzyme at sites 19 and 40. Furthermore, endothelins enhanced norepinephrine release in olfactory neurons suggesting that this event may contribute to increased tyrosine hydroxylase activity by reducing the feedback inhibition. Taken together present findings show a clear interaction between the endothelin system, and the catecholaminergic transmission in the olfactory bulb. Additional studies are required to evaluate the physiological functions regulated by endothelins at this brain level.

  6. Bifurcation analysis of oscillating network model of pattern recognition in the rabbit olfactory bulb

    NASA Astrophysics Data System (ADS)

    Baird, Bill

    1986-08-01

    A neural network model describing pattern recognition in the rabbit olfactory bulb is analysed to explain the changes in neural activity observed experimentally during classical Pavlovian conditioning. EEG activity recorded from an 8×8 arry of 64 electrodes directly on the surface on the bulb shows distinct spatial patterns of oscillation that correspond to the animal's recognition of different conditioned odors and change with conditioning to new odors. The model may be considered a variant of Hopfield's model of continuous analog neural dynamics. Excitatory and inhibitory cell types in the bulb and the anatomical architecture of their connection requires a nonsymmetric coupling matrix. As the mean input level rises during each breath of the animal, the system bifurcates from homogenous equilibrium to a spatially patterned oscillation. The theory of multiple Hopf bifurcations is employed to find coupled equations for the amplitudes of these unstable oscillatory modes independent of frequency. This allows a view of stored periodic attractors as fixed points of a gradient vector field and thereby recovers the more familiar dynamical systems picture of associative memory.

  7. The functional significance of newly born neurons integrated into olfactory bulb circuits

    PubMed Central

    Sakamoto, Masayuki; Kageyama, Ryoichiro; Imayoshi, Itaru

    2014-01-01

    The olfactory bulb (OB) is the first central processing center for olfactory information connecting with higher areas in the brain, and this neuronal circuitry mediates a variety of odor-evoked behavioral responses. In the adult mammalian brain, continuous neurogenesis occurs in two restricted regions, the subventricular zone (SVZ) of the lateral ventricle and the hippocampal dentate gyrus. New neurons born in the SVZ migrate through the rostral migratory stream and are integrated into the neuronal circuits of the OB throughout life. The significance of this continuous supply of new neurons in the OB has been implicated in plasticity and memory regulation. Two decades of huge investigation in adult neurogenesis revealed the biological importance of integration of new neurons into the olfactory circuits. In this review, we highlight the recent findings about the physiological functions of newly generated neurons in rodent OB circuits and then discuss the contribution of neurogenesis in the brain function. Finally, we introduce cutting edge technologies to monitor and manipulate the activity of new neurons. PMID:24904263

  8. Recording Temperature-induced Neuronal Activity through Monitoring Calcium Changes in the Olfactory Bulb of Xenopus laevis

    PubMed Central

    Kludt, Eugen; Schild, Detlev

    2016-01-01

    The olfactory system, specialized in the detection, integration and processing of chemical molecules is likely the most thoroughly studied sensory system. However, there is piling evidence that olfaction is not solely limited to chemical sensitivity, but also includes temperature sensitivity. Premetamorphic Xenopus laevis are translucent animals, with protruding nasal cavities deprived of the cribriform plate separating the nose and the olfactory bulb. These characteristics make them well suited for studying olfaction, and particularly thermosensitivity. The present article describes the complete procedure for measuring temperature responses in the olfactory bulb of X. laevis larvae. Firstly, the electroporation of olfactory receptor neurons (ORNs) is performed with spectrally distinct dyes loaded into the nasal cavities in order to stain their axon terminals in the bulbar neuropil. The differential staining between left and right receptor neurons serves to identify the γ-glomerulus as the only structure innervated by contralateral presynaptic afferents. Secondly, the electroporation is combined with focal bolus loading in the olfactory bulb in order to stain mitral cells and their dendrites. The 3D brain volume is then scanned under line-illumination microscopy for the acquisition of fast calcium imaging data while small temperature drops are induced at the olfactory epithelium. Lastly, the post-acquisition analysis allows the morphological reconstruction of the thermosensitive network comprising the γ-glomerulus and its innervating mitral cells, based on specific temperature-induced Ca2+ traces. Using chemical odorants as stimuli in addition to temperature jumps enables the comparison between thermosensitive and chemosensitive networks in the olfactory bulb. PMID:27286501

  9. Recording Temperature-induced Neuronal Activity through Monitoring Calcium Changes in the Olfactory Bulb of Xenopus laevis.

    PubMed

    Brinkmann, Alexander; Okom, Camille; Kludt, Eugen; Schild, Detlev

    2016-01-01

    The olfactory system, specialized in the detection, integration and processing of chemical molecules is likely the most thoroughly studied sensory system. However, there is piling evidence that olfaction is not solely limited to chemical sensitivity, but also includes temperature sensitivity. Premetamorphic Xenopus laevis are translucent animals, with protruding nasal cavities deprived of the cribriform plate separating the nose and the olfactory bulb. These characteristics make them well suited for studying olfaction, and particularly thermosensitivity. The present article describes the complete procedure for measuring temperature responses in the olfactory bulb of X. laevis larvae. Firstly, the electroporation of olfactory receptor neurons (ORNs) is performed with spectrally distinct dyes loaded into the nasal cavities in order to stain their axon terminals in the bulbar neuropil. The differential staining between left and right receptor neurons serves to identify the γ-glomerulus as the only structure innervated by contralateral presynaptic afferents. Secondly, the electroporation is combined with focal bolus loading in the olfactory bulb in order to stain mitral cells and their dendrites. The 3D brain volume is then scanned under line-illumination microscopy for the acquisition of fast calcium imaging data while small temperature drops are induced at the olfactory epithelium. Lastly, the post-acquisition analysis allows the morphological reconstruction of the thermosensitive network comprising the γ-glomerulus and its innervating mitral cells, based on specific temperature-induced Ca(2+) traces. Using chemical odorants as stimuli in addition to temperature jumps enables the comparison between thermosensitive and chemosensitive networks in the olfactory bulb. PMID:27286501

  10. Greater addition of neurons to the olfactory bulb than to the cerebral cortex of eulipotyphlans but not rodents, afrotherians or primates

    PubMed Central

    Ribeiro, Pedro F. M.; Manger, Paul R.; Catania, Kenneth C.; Kaas, Jon H.; Herculano-Houzel, Suzana

    2014-01-01

    The olfactory bulb is an evolutionarily old structure that antedates the appearance of a six-layered mammalian cerebral cortex. As such, the neuronal scaling rules that apply to scaling the mass of the olfactory bulb as a function of its number of neurons might be shared across mammalian groups, as we have found to be the case for the ensemble of non-cortical, non-cerebellar brain structures. Alternatively, the neuronal scaling rules that apply to the olfactory bulb might be distinct in those mammals that rely heavily on olfaction. The group previously referred to as Insectivora includes small mammals, some of which are now placed in Afrotheria, a base group in mammalian radiation, and others in Eulipotyphla, a group derived later, at the base of Laurasiatheria. Here we show that the neuronal scaling rules that apply to building the olfactory bulb differ across eulipotyphlans and other mammals such that eulipotyphlans have more neurons concentrated in an olfactory bulb of similar size than afrotherians, glires and primates. Most strikingly, while the cerebral cortex gains neurons at a faster pace than the olfactory bulb in glires, and afrotherians follow this trend, it is the olfactory bulb that gains neurons at a faster pace than the cerebral cortex in eulipotyphlans, which contradicts the common view that the cerebral cortex is the fastest expanding structure in brain evolution. Our findings emphasize the importance of not using brain structure size as a proxy for numbers of neurons across mammalian orders, and are consistent with the notion that different selective pressures have acted upon the olfactory system of eulipotyphlans, glires and primates, with eulipotyphlans relying more on olfaction for their behavior than glires and primates. Surprisingly, however, the neuronal scaling rules for primates predict that the human olfactory bulb has as many neurons as the larger eulipotyphlan olfactory bulbs, which questions the classification of humans as microsmatic

  11. Transcriptome profile and cytogenetic analysis of immortalized neuronally restricted progenitor cells derived from the porcine olfactory bulb

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recently, we established and phenotypically characterized an immortalized porcine olfactory bulb neuroblast cell line, OBGF400 (Uebing-Czipura et al., 2008). To facilitate the future application of these cells in studies of neurological dysfunction and neuronal replacement therapies, a comprehensive...

  12. In vivo Growth and Differentiation of Canine Olfactory Bulb-Derived Neural Progenitor Cells under Variable Culture Conditions

    PubMed Central

    Walton, Raquel M.; Wolfe, John H.

    2008-01-01

    The dog serves as a large animal model for multiple neurologic diseases that may potentially benefit from neural progenitor cell (NPC) transplantation. In the adult brain, multipotent NPCs reside in the subventricular zone and its rostral and caudal extensions into the olfactory bulb and hippocampus. The olfactory bulb represents a surgically accessible site for obtaining cells for autologous NPC transplantation. To model conditions that would occur for ex vivo gene therapy in the postnatal brain, NPCs were isolated from the canine olfactory bulb, expanded ex vivo under different culture conditions, and compared quantitatively for growth and immunophenotype. Under standard growth conditions, canine olfactory bulb-derived NPCs (OB-cNPCs) could be expanded nearly 500-fold in the time evaluated. Canine OB-cNPCs grown on poly-D-lysine (PDL) or on PDL-fibronectin had similar growth rates, whereas supplementation with leukemia inhibitory factor (LIF) resulted in significantly slower growth. However, when OB-cNPC cultures were grown on PDL-fibronectin or PDL supplemented with LIF, a greater proportion of cells with neuronal markers were generated upon differentiation. PMID:18261803

  13. The Role of Astrocytes in the Generation, Migration, and Integration of New Neurons in the Adult Olfactory Bulb

    PubMed Central

    Gengatharan, Archana; Bammann, Rodrigo R.; Saghatelyan, Armen

    2016-01-01

    In mammals, new neurons in the adult olfactory bulb originate from a pool of neural stem cells in the subventricular zone of the lateral ventricles. Adult-born cells play an important role in odor information processing by adjusting the neuronal network to changing environmental conditions. Olfactory bulb neurogenesis is supported by several non-neuronal cells. In this review, we focus on the role of astroglial cells in the generation, migration, integration, and survival of new neurons in the adult forebrain. In the subventricular zone, neural stem cells with astrocytic properties display regional and temporal specificity when generating different neuronal subtypes. Non-neurogenic astrocytes contribute to the establishment and maintenance of the neurogenic niche. Neuroblast chains migrate through the rostral migratory stream ensheathed by astrocytic processes. Astrocytes play an important regulatory role in neuroblast migration and also assist in the development of a vasculature scaffold in the migratory stream that is essential for neuroblast migration in the postnatal brain. In the olfactory bulb, astrocytes help to modulate the network through a complex release of cytokines, regulate blood flow, and provide metabolic support, which may promote the integration and survival of new neurons. Astrocytes thus play a pivotal role in various processes of adult olfactory bulb neurogenesis, and it is likely that many other functions of these glial cells will emerge in the near future. PMID:27092050

  14. Changes in neurotransmitter levels and proinflammatory cytokine mRNA expressions in the mice olfactory bulb following nanoparticle exposure

    SciTech Connect

    Tin-Tin-Win-Shwe Mitsushima, Dai; Yamamoto, Shoji; Fukushima, Atsushi; Funabashi, Toshiya; Kobayashi, Takahiro; Fujimaki, Hidekazu

    2008-01-15

    Recently, there have been increasing reports that nano-sized component of particulate matter can reach the brain and may be associated with neurodegenerative diseases. Previously, our laboratory has studied the effect of intranasal instillation of nano-sized carbon black (CB) (14 nm and 95 nm) on brain cytokine and chemokine mRNA expressions and found that 14-nm CB increased IL-1{beta}, TNF-{alpha}, CCL2 and CCL3 mRNA expressions in the olfactory bulb, not in the hippocampus of mice. To investigate the effect of a single administration of nanoparticles on neurotransmitters and proinflammatory cytokines in a mouse olfactory bulb, we performed in vivo microdialysis and real-time PCR methods. Ten-week-old male BALB/c mice were implanted with guide cannula in the right olfactory bulb and, 1 week later, were instilled vehicle or CB (14 nm, 250 {mu}g) intranasally. Six hours after the nanoparticle instillation, the mice were intraperitoneally injected with normal saline or 50 {mu}g of bacteria cell wall component lipoteichoic acid (LTA), which may potentiate CB-induced neurologic effect. Extracellular glutamate and glycine levels were significantly increased in the olfactory bulb of CB-instilled mice when compared with vehicle-instilled control mice. Moreover, we found that LTA further increased glutamate and glycine levels. However, no alteration of taurine and GABA levels was observed in the olfactory bulb of the same mice. We also detected immunological changes in the olfactory bulb 11 h after vehicle or CB instillation and found that IL-1{beta} mRNA expression was significantly increased in CB- and LTA-treated mice when compared with control group. However, TNF-{alpha} mRNA expression was increased significantly in CB- and saline-treated mice when compared with control group. These findings suggest that nanoparticle CB may modulate the extracellular amino acid neurotransmitter levels and proinflammatory cytokine IL-1 {beta} mRNA expressions synergistically with LTA

  15. Amyloid Beta Inhibits Olfactory Bulb Activity and the Ability to Smell

    PubMed Central

    Peña-Ortega, Fernando

    2013-01-01

    Early olfactory dysfunction has been consistently reported in both Alzheimer’s disease (AD) and in transgenic mice that reproduce some features of this disease. In AD transgenic mice, alteration in olfaction has been associated with increased levels of soluble amyloid beta protein (Aβ) as well as with alterations in the oscillatory network activity recorded in the olfactory bulb (OB) and in the piriform cortex. However, since AD is a multifactorial disease and transgenic mice suffer a variety of adaptive changes, it is still unknown if soluble Aβ, by itself, is responsible for OB dysfunction both at electrophysiological and behavioral levels. Thus, here we tested whether or not Aβ directly affects OB network activity in vitro in slices obtained from mice and rats and if it affects olfactory ability in these rodents. Our results show that Aβ decreases, in a concentration- and time-dependent manner, the network activity of OB slices at clinically relevant concentrations (low nM) and in a reversible manner. Moreover, we found that intrabulbar injection of Aβ decreases the olfactory ability of rodents two weeks after application, an effect that is not related to alterations in motor performance or motivation to seek food and that correlates with the presence of Aβ deposits. Our results indicate that Aβ disrupts, at clinically relevant concentrations, the network activity of the OB in vitro and can trigger a disruption in olfaction. These findings open the possibility of exploring the cellular mechanisms involved in early pathological AD as an approach to reduce or halt its progress. PMID:24086624

  16. Functional recovery of odor representations in regenerated sensory inputs to the olfactory bulb

    PubMed Central

    Cheung, Man C.; Jang, Woochan; Schwob, James E.; Wachowiak, Matt

    2014-01-01

    The olfactory system has a unique capacity for recovery from peripheral damage. After injury to the olfactory epithelium (OE), olfactory sensory neurons (OSNs) regenerate and re-converge on target glomeruli of the olfactory bulb (OB). Thus far, this process has been described anatomically for only a few defined populations of OSNs. Here we characterize this regeneration at a functional level by assessing how odor representations carried by OSN inputs to the OB recover after massive loss and regeneration of the sensory neuron population. We used chronic imaging of mice expressing synaptopHluorin in OSNs to monitor odor representations in the dorsal OB before lesion by the olfactotoxin methyl bromide and after a 12 week recovery period. Methyl bromide eliminated functional inputs to the OB, and these inputs recovered to near-normal levels of response magnitude within 12 weeks. We also found that the functional topography of odor representations recovered after lesion, with odorants evoking OSN input to glomerular foci within the same functional domains as before lesion. At a finer spatial scale, however, we found evidence for mistargeting of regenerated OSN axons onto OB targets, with odorants evoking synaptopHluorin signals in small foci that did not conform to a typical glomerular structure but whose distribution was nonetheless odorant-specific. These results indicate that OSNs have a robust ability to reestablish functional inputs to the OB and that the mechanisms underlying the topography of bulbar reinnervation during development persist in the adult and allow primary sensory representations to be largely restored after massive sensory neuron loss. PMID:24431990

  17. Insulin modulates network activity in olfactory bulb slices: impact on odour processing.

    PubMed

    Kuczewski, Nicola; Fourcaud-Trocmé, Nicolas; Savigner, Agnès; Thevenet, Marc; Aimé, Pascaline; Garcia, Samuel; Duchamp-Viret, Patricia; Palouzier-Paulignan, Brigitte

    2014-07-01

    Odour perception depends closely on nutritional status, in animals as in humans. Insulin, the principal anorectic hormone, appears to be one of the major candidates for ensuring the link between olfactory abilities and nutritional status, by modifying processing in the olfactory bulb (OB), one of its main central targets. The present study investigates whether and how insulin can act in OB, by evaluating its action on the main output neurons activities, mitral cells (MCs), in acute rat OB slices. Insulin was found to act at two OB network levels: (1) on MCs, by increasing their excitability, probably by inhibiting two voltage-gated potassium (K(+)) channels; (2) on interneurons by modifying the GABAergic and on glutamatergic synaptic activity impinging on MCs, mainly reducing them. Insulin also altered the olfactory nerve (ON)-evoked excitatory postsynaptic currents in 60% of MCs. Insulin decreased or increased the ON-evoked responses in equal proportion and the direction of its effect depended on the initial neuron ON-evoked firing rate. Indeed, insulin tended to decrease the high and to increase the low ON-evoked firing rates, thereby reducing inter-MC response firing variability. Therefore, the effects of insulin on the evoked firing rates were not carried out indiscriminately in the MC population. By constructing a mathematical model, the impact of insulin complex effects on OB was assessed at the population activity level. The model shows that the reduction of variability across cells could affect MC detection and discrimination abilities, mainly by decreasing and, less frequently, increasing them, depending on odour quality. Thus, as previously proposed, this differential action of insulin on MCs across odours would allow this hormone to put the olfactory function under feeding signal control, given the discerning valence of an odour as a function of nutritional status. PMID:24710056

  18. Individual and synergistic effects of sniffing frequency and flow rate on olfactory bulb activity.

    PubMed

    Courtiol, Emmanuelle; Hegoburu, Chloé; Litaudon, Philippe; Garcia, Samuel; Fourcaud-Trocmé, Nicolas; Buonviso, Nathalie

    2011-12-01

    Is faster or stronger sniffing important for the olfactory system? Odorant molecules are captured by sniffing. The features of sniffing constrain both the temporality and intensity of the input to the olfactory structures. In this context, it is clear that variations in both the sniff frequency and flow rate have a major impact on the activation of olfactory structures. However, the question of how frequency and flow rate individually or synergistically impact bulbar output has not been answered. We have addressed this question using multiple experimental approaches. In double-tracheotomized, anesthetized rats, we recorded both the bulbar local field potential (LFP) and mitral/tufted cells' activities when the sampling flow rate and frequency were controlled independently. We found that a tradeoff between the sampling frequency and the flow rate could maintain olfactory bulb sampling-related rhythmicity and that only an increase in flow rate could induce a faster, odor-evoked response. LFP and sniffing were recorded in awake rats. We found that sampling-related rhythmicity was maintained during high-frequency sniffing. Furthermore, we observed that the covariation between the frequency and flow rate, which was necessary for the tradeoff seen in the anesthetized preparations, also occurred in awake animals. Our study shows that the sampling frequency and flow rate can act either independently or synergistically on bulbar output to shape the neuronal message. The system likely takes advantage of this flexibility to adapt sniffing strategies to animal behavior. Our study provides additional support for the idea that sniffing and olfaction function in an integrated manner.

  19. The effect of some drugs on the mitral cell odor-evoked responses in the gecko olfactory bulb.

    PubMed

    Tonosaki, K; Shibuya, T

    1985-01-01

    The activity of odor-evoked olfactory mitral cell response of the gecko was recorded extracellularly by glass microelectrodes. The activities of the mitral cell observed during the presentation of the odor (n-amyl acetate) could be described as excitation, suppression or zero. The present experiments were undertaken to study the neural activities of the mitral cell in the olfactory bulb by perfusion application of some drugs (cobalt chloride, carnosine, norepinephrine, GABA and D-L-homocysteate) on the olfactory bulb surface or iontophoretic application of some drugs (carnosine, norepinephrine, GABA and D-L-homocysteate) to the glomerulus and the external plexiform layer to change the physiological environment. The effect of the drugs suggested that the synaptic neurons on the mitral cell have different chemical characteristics.

  20. Combinatorial and chemotopic odorant coding in the zebrafish olfactory bulb visualized by optical imaging.

    PubMed

    Friedrich, R W; Korsching, S I

    1997-05-01

    Odors are thought to be represented by a distributed code across the glomerular modules in the olfactory bulb (OB). Here, we optically imaged presynaptic activity in glomerular modules of the zebrafish OB induced by a class of natural odorants (amino acids [AAs]) after labeling of primary afferents with a calcium-sensitive dye. AAs induce complex combinatorial patterns of active glomerular modules that are unique for different stimuli and concentrations. Quantitative analysis shows that defined molecular features of stimuli are correlated with activity in spatially confined groups of glomerular modules. These results provide direct evidence that identity and concentration of odorants are encoded by glomerular activity patterns and reveal a coarse chemotopic organization of the array of glomerular modules.

  1. Dynamic Sensory Representations in the Olfactory Bulb: Modulation by Wakefulness and Experience

    PubMed Central

    Kato, Hiroyuki K.; Chu, Monica W.; Isaacson, Jeffry S.; Komiyama, Takaki

    2012-01-01

    SUMMARY How are sensory representations in the brain influenced by the state of an animal? Here we use chronic two-photon calcium imaging to explore how wakefulness and experience shape odor representations in the mouse olfactory bulb. Comparing the awake and anesthetized state, we show that wakefulness greatly enhances the activity of inhibitory granule cells and makes principal mitral cell odor responses more sparse and temporally dynamic. In awake mice, brief repeated odor experience leads to a gradual and long-lasting (months) weakening of mitral cell odor representations. This mitral cell plasticity is odor-specific, recovers gradually over months and can be repeated with different odors. Furthermore, the expression of this experience-dependent plasticity is prevented by anesthesia. Together, our results demonstrate the dynamic nature of mitral cell odor representations in awake animals, which is constantly shaped by recent odor experience. PMID:23217744

  2. An interglomerular circuit gates glomerular output and implements gain control in the mouse olfactory bulb

    PubMed Central

    Banerjee, Arkarup; Marbach, Fred; Anselmi, Francesca; Koh, Matthew S.; Davis, Martin B.; da Silva, Pedro Garcia; Delevich, Kristen; Oyibo, Hassana K.; Gupta, Priyanka; Li, Bo; Albeanu, Dinu F.

    2015-01-01

    Summary Odors elicit distributed activation of glomeruli in the olfactory bulb (OB). Crosstalk between co-active glomeruli has been proposed to perform a variety of computations, facilitating efficient extraction of sensory information by the cortex. Dopaminergic/GABAergic cells in the OB, which can be identified by their expression of the dopamine transporter (DAT), provide the earliest opportunity for such crosstalk. Here we show in mice that DAT+ cells carry concentration dependent odor signals and broadcast focal glomerular inputs throughout the OB to cause suppression of mitral/tufted (M/T) cell firing, an effect that is mediated by the external tufted (ET) cells coupled to DAT+ cells via chemical and electrical synapses. We find that DAT+ cells implement gain control and decorrelate odor representations in the M/T cell population. Our results further indicate that ET cells are gatekeepers of glomerular output and prime determinants of M/T responsiveness. PMID:26139373

  3. Control of Mitral/Tufted Cell Output by Selective Inhibition among Olfactory Bulb Glomeruli.

    PubMed

    Economo, Michael N; Hansen, Kyle R; Wachowiak, Matt

    2016-07-20

    Inhibition is fundamental to information processing by neural circuits. In the olfactory bulb (OB), glomeruli are the functional units for odor information coding, but inhibition among glomeruli is poorly characterized. We used two-photon calcium imaging in anesthetized and awake mice to visualize both odorant-evoked excitation and suppression in OB output neurons (mitral and tufted, MT cells). MT cell response polarity mapped uniformly to discrete OB glomeruli, allowing us to analyze how inhibition shapes OB output relative to the glomerular map. Odorants elicited unique patterns of suppression in only a subset of glomeruli in which such suppression could be detected, and excited and suppressed glomeruli were spatially intermingled. Binary mixture experiments revealed that interglomerular inhibition could suppress excitatory mitral cell responses to odorants. These results reveal that inhibitory OB circuits nonlinearly transform odor representations and support a model of selective and nonrandom inhibition among glomerular ensembles. PMID:27346531

  4. Human olfactory bulb neural stem cells mitigate movement disorders in a rat model of Parkinson's disease.

    PubMed

    Marei, Hany E S; Lashen, Samah; Farag, Amany; Althani, Asmaa; Afifi, Nahla; A, Abd-Elmaksoud; Rezk, Shaymaa; Pallini, Roberto; Casalbore, Patrizia; Cenciarelli, Carlo

    2015-07-01

    Parkinson's disease (PD) is a neurological disorder characterized by the loss of midbrain dopaminergic (DA) neurons. Neural stem cells (NSCs) are multipotent stem cells that are capable of differentiating into different neuronal and glial elements. The production of DA neurons from NSCs could potentially alleviate behavioral deficits in Parkinsonian patients; timely intervention with NSCs might provide a therapeutic strategy for PD. We have isolated and generated highly enriched cultures of neural stem/progenitor cells from the human olfactory bulb (OB). If NSCs can be obtained from OB, it would alleviate ethical concerns associated with the use of embryonic tissue, and provide an easily accessible cell source that would preclude the need for invasive brain surgery. Following isolation and culture, olfactory bulb neural stem cells (OBNSCs) were genetically engineered to express hNGF and GFP. The hNFG-GFP-OBNSCs were transplanted into the striatum of 6-hydroxydopamin (6-OHDA) Parkinsonian rats. The grafted cells survived in the lesion environment for more than eight weeks after implantation with no tumor formation. The grafted cells differentiated in vivo into oligodendrocyte-like (25 ± 2.88%), neuron-like (52.63 ± 4.16%), and astrocyte -like (22.36 ± 1.56%) lineages, which we differentiated based on morphological and immunohistochemical criteria. Transplanted rats exhibited a significant partial correction in stepping and placing in non-pharmacological behavioral tests, pole and rotarod tests. Taken together, our data encourage further investigations of the possible use of OBNSCs as a promising cell-based therapeutic strategy for Parkinson's disease.

  5. Spatio-Temporal Characteristics of Inhibition Mapped by Optical Stimulation in Mouse Olfactory Bulb

    PubMed Central

    Lehmann, Alexander; D’Errico, Anna; Vogel, Martin; Spors, Hartwig

    2016-01-01

    Mitral and tufted cells (MTCs) of the mammalian olfactory bulb are connected via dendrodendritic synapses with inhibitory interneurons in the external plexiform layer. The range, spatial layout, and temporal properties of inhibitory interactions between MTCs mediated by inhibitory interneurons remain unclear. Therefore, we tested for inhibitory interactions using an optogenetic approach. We optically stimulated MTCs expressing channelrhodopsin-2 in transgenic mice, while recording from individual MTCs in juxtacellular or whole-cell configuration in vivo. We used a spatial noise stimulus for mapping interactions between MTCs belonging to different glomeruli in the dorsal bulb. Analyzing firing responses of MTCs to the stimulus, we did not find robust lateral inhibitory effects that were spatially specific. However, analysis of sub-threshold changes in the membrane potential revealed evidence for inhibitory interactions between MTCs that belong to different glomerular units. These lateral inhibitory effects were short-lived and spatially specific. MTC response maps showed hyperpolarizing effects radially extending over more than five glomerular diameters. The inhibitory maps exhibited non-symmetrical yet distance-dependent characteristics. PMID:27047340

  6. Transcription factors expressed in olfactory bulb local progenitor cells revealed by genome-wide transcriptome profiling

    PubMed Central

    Campbell, Gordon R. O.; Baudhuin, Ariane; Vranizan, Karen; Ngai, John

    2011-01-01

    The local progenitor population in the olfactory bulb (OB) gives rise to mitral and tufted projection neurons during embryonic development. In contrast, OB interneurons are derived from sources outside the bulb where neurogenesis continues throughout life. While many of the genes involved in OB interneuron development have been characterized, the genetic pathways driving local progenitor cell differentiation in this tissue are largely unknown. To better understand this process, we used transcriptional profiling to monitor gene expression of whole OB at daily intervals from embryonic day 11 through birth, generating a compendium of gene expression encompassing the major developmental events of this tissue. Through hierarchical clustering, bioinformatics analysis, and validation by RNA in situ hybridizations, we identified a large number of transcription factors, DNA binding proteins, and cell cycle-related genes expressed by the local neural progenitor cells (NPCs) of the embryonic OB. Further in silico analysis of transcription factor binding sites identified an enrichment of genes regulated by the E2F-Rb pathway among those expressed in the local NPC population. Together these results provide initial insights into the molecular identity of the OB local NPC population and the transcription factor networks that may regulate their function. PMID:21194568

  7. Ex vivo preparations of the intact vomeronasal organ and accessory olfactory bulb.

    PubMed

    Doyle, Wayne I; Hammen, Gary F; Meeks, Julian P

    2014-01-01

    The mouse accessory olfactory system (AOS) is a specialized sensory pathway for detecting nonvolatile social odors, pheromones, and kairomones. The first neural circuit in the AOS pathway, called the accessory olfactory bulb (AOB), plays an important role in establishing sex-typical behaviors such as territorial aggression and mating. This small (<1 mm(3)) circuit possesses the capacity to distinguish unique behavioral states, such as sex, strain, and stress from chemosensory cues in the secretions and excretions of conspecifics. While the compact organization of this system presents unique opportunities for recording from large portions of the circuit simultaneously, investigation of sensory processing in the AOB remains challenging, largely due to its experimentally disadvantageous location in the brain. Here, we demonstrate a multi-stage dissection that removes the intact AOB inside a single hemisphere of the anterior mouse skull, leaving connections to both the peripheral vomeronasal sensory neurons (VSNs) and local neuronal circuitry intact. The procedure exposes the AOB surface to direct visual inspection, facilitating electrophysiological and optical recordings from AOB circuit elements in the absence of anesthetics. Upon inserting a thin cannula into the vomeronasal organ (VNO), which houses the VSNs, one can directly expose the periphery to social odors and pheromones while recording downstream activity in the AOB. This procedure enables controlled inquiries into AOS information processing, which can shed light on mechanisms linking pheromone exposure to changes in behavior.

  8. The interplay between reproductive social stimuli and adult olfactory bulb neurogenesis.

    PubMed

    Peretto, Paolo; Schellino, Roberta; De Marchis, Silvia; Fasolo, Aldo

    2014-01-01

    Adult neurogenesis is a striking form of structural plasticity that adapts the brain to the changing world. Accordingly, new neuron production is involved in cognitive functions, such as memory, learning, and pattern separation. Recent data in rodents indicate a close link between adult neurogenesis and reproductive social behavior. This provides a key to unravel the functional meaning of adult neurogenesis in biological relevant contexts and, in parallel, opens new perspectives to explore the way the brain is processing social stimuli. In this paper we will summarize some of the major achievements on cues and mechanisms modulating adult neurogenesis during social behaviors related to reproduction and possible role/s played by olfactory newborn neurons in this context. We will point out that newborn interneurons in the accessory olfactory bulb (AOB) represent a privileged cellular target for social stimuli that elicit reproductive behaviors and that such cues modulate adult neurogenesis at two different levels increasing both proliferation of neuronal progenitors in the germinative regions and integration of newborn neurons into functional circuits. This dual mechanism provides fresh neurons that can be involved in critical activities for the individual fitness, that is, the processing of social stimuli driving the parental behavior and partner recognition.

  9. Diabetes Impairs Wnt3 Protein-induced Neurogenesis in Olfactory Bulbs via Glutamate Transporter 1 Inhibition.

    PubMed

    Wakabayashi, Tamami; Hidaka, Ryo; Fujimaki, Shin; Asashima, Makoto; Kuwabara, Tomoko

    2016-07-15

    Diabetes is associated with impaired cognitive function. Streptozotocin (STZ)-induced diabetic rats exhibit a loss of neurogenesis and deficits in behavioral tasks involving spatial learning and memory; thus, impaired adult hippocampal neurogenesis may contribute to diabetes-associated cognitive deficits. Recent studies have demonstrated that adult neurogenesis generally occurs in the dentate gyrus of the hippocampus, the subventricular zone, and the olfactory bulbs (OB) and is defective in patients with diabetes. We hypothesized that OB neurogenesis and associated behaviors would be affected in diabetes. In this study, we show that inhibition of Wnt3-induced neurogenesis in the OB causes several behavioral deficits in STZ-induced diabetic rats, including impaired odor discrimination, cognitive dysfunction, and increased anxiety. Notably, the sodium- and chloride-dependent GABA transporters and excitatory amino acid transporters that localize to GABAergic and glutamatergic terminals decreased in the OB of diabetic rats. Moreover, GAT1 inhibitor administration also hindered Wnt3-induced neurogenesis in vitro Collectively, these data suggest that STZ-induced diabetes adversely affects OB neurogenesis via GABA and glutamate transporter systems, leading to functional impairments in olfactory performance. PMID:27226528

  10. Ex vivo preparations of the intact vomeronasal organ and accessory olfactory bulb.

    PubMed

    Doyle, Wayne I; Hammen, Gary F; Meeks, Julian P

    2014-01-01

    The mouse accessory olfactory system (AOS) is a specialized sensory pathway for detecting nonvolatile social odors, pheromones, and kairomones. The first neural circuit in the AOS pathway, called the accessory olfactory bulb (AOB), plays an important role in establishing sex-typical behaviors such as territorial aggression and mating. This small (<1 mm(3)) circuit possesses the capacity to distinguish unique behavioral states, such as sex, strain, and stress from chemosensory cues in the secretions and excretions of conspecifics. While the compact organization of this system presents unique opportunities for recording from large portions of the circuit simultaneously, investigation of sensory processing in the AOB remains challenging, largely due to its experimentally disadvantageous location in the brain. Here, we demonstrate a multi-stage dissection that removes the intact AOB inside a single hemisphere of the anterior mouse skull, leaving connections to both the peripheral vomeronasal sensory neurons (VSNs) and local neuronal circuitry intact. The procedure exposes the AOB surface to direct visual inspection, facilitating electrophysiological and optical recordings from AOB circuit elements in the absence of anesthetics. Upon inserting a thin cannula into the vomeronasal organ (VNO), which houses the VSNs, one can directly expose the periphery to social odors and pheromones while recording downstream activity in the AOB. This procedure enables controlled inquiries into AOS information processing, which can shed light on mechanisms linking pheromone exposure to changes in behavior. PMID:25145699

  11. Pink1-deficiency in mice impairs gait, olfaction and serotonergic innervation of the olfactory bulb.

    PubMed

    Glasl, Lisa; Kloos, Karina; Giesert, Florian; Roethig, Anne; Di Benedetto, Barbara; Kühn, Ralf; Zhang, Jingzhong; Hafen, Ulrich; Zerle, Julia; Hofmann, Andreas; de Angelis, Martin Hrabé; Winklhofer, Konstanze F; Hölter, Sabine M; Vogt Weisenhorn, Daniela M; Wurst, Wolfgang

    2012-05-01

    Parkinson's Disease (PD) is the most common neurodegenerative movement disorder. Autosomal-recessive mutations in the mitochondrial protein kinase PINK1 (PTEN-induced kinase 1) account for 1-2% of the hereditary early-onset cases. To study the mechanisms underlying disease development, we generated Pink1-deficient mice. In analogy to other genetic loss-of-function mouse models, Pink1(-/-) mice did not show morphological alterations in the dopaminergic system. As a consequence, no gross motor dysfunctions were observed indicating that these mice do not develop the cardinal symptoms of PD. Nonetheless, symptoms which develop mainly before bradykinesia, rigidity and resting tremor were clearly evident in Pink1-deficient mice. These symptoms were gait alterations and olfactory dysfunctions. Remarkably in the glomerular layer of the olfactory bulb the density of serotonergic fibers was significantly reduced. Concerning mitochondrial morphology, neurons in Pink1(-/-) mice had less fragmented mitochondria. In contrast, upon acute knock-down of Pink1 increased mitochondrial fragmentation was observed in neuronal cultures. This fragmentation was, however, evened out within days. Taken together, we demonstrate that Pink1-deficient mice exhibit behavioral symptoms of early phases of PD and present systematic experimental evidence for compensation of Pink1-deficiency at the cellular level. Thus, Pink1-deficient mice represent a model for the early phases of PD in which compensation may still impede the onset of neurodegeneration. Consequently, these mice are a valuable tool for studying Pink1-related PD development, as well as for searching for reliable PD biomarkers.

  12. Ex Vivo Preparations of the Intact Vomeronasal Organ and Accessory Olfactory Bulb

    PubMed Central

    Doyle, Wayne I.; Hammen, Gary F.; Meeks, Julian P.

    2014-01-01

    The mouse accessory olfactory system (AOS) is a specialized sensory pathway for detecting nonvolatile social odors, pheromones, and kairomones. The first neural circuit in the AOS pathway, called the accessory olfactory bulb (AOB), plays an important role in establishing sex-typical behaviors such as territorial aggression and mating. This small (<1 mm3) circuit possesses the capacity to distinguish unique behavioral states, such as sex, strain, and stress from chemosensory cues in the secretions and excretions of conspecifics. While the compact organization of this system presents unique opportunities for recording from large portions of the circuit simultaneously, investigation of sensory processing in the AOB remains challenging, largely due to its experimentally disadvantageous location in the brain. Here, we demonstrate a multi-stage dissection that removes the intact AOB inside a single hemisphere of the anterior mouse skull, leaving connections to both the peripheral vomeronasal sensory neurons (VSNs) and local neuronal circuitry intact. The procedure exposes the AOB surface to direct visual inspection, facilitating electrophysiological and optical recordings from AOB circuit elements in the absence of anesthetics. Upon inserting a thin cannula into the vomeronasal organ (VNO), which houses the VSNs, one can directly expose the periphery to social odors and pheromones while recording downstream activity in the AOB. This procedure enables controlled inquiries into AOS information processing, which can shed light on mechanisms linking pheromone exposure to changes in behavior. PMID:25145699

  13. Distinct spatiotemporal activity in principal neurons of the mouse olfactory bulb in anesthetized and awake states

    PubMed Central

    Blauvelt, David G.; Sato, Tomokazu F.; Wienisch, Martin; Murthy, Venkatesh N.

    2013-01-01

    The acquisition of olfactory information and its early processing in mammals are modulated by brain states through sniffing behavior and neural feedback. We imaged the spatiotemporal pattern of odor-evoked activity in a population of output neurons (mitral/tufted cells, MTCs) in the olfactory bulb (OB) of head-restrained mice expressing a genetically-encoded calcium indicator. The temporal dynamics of MTC population activity were relatively simple in anesthetized animals, but were highly variable in awake animals. However, the apparently irregular activity in awake animals could be predicted well using sniff timing measured externally, or inferred through fluctuations in the global responses of MTC population even without explicit knowledge of sniff times. The overall spatial pattern of activity was conserved across states, but odor responses had a diffuse spatial component in anesthetized mice that was less prominent during wakefulness. Multi-photon microscopy indicated that MTC lateral dendrites were the likely source of spatially disperse responses in the anesthetized animal. Our data demonstrate that the temporal and spatial dynamics of MTCs can be significantly modulated by behavioral state, and that the ensemble activity of MTCs can provide information about sniff timing to downstream circuits to help decode odor responses. PMID:23543674

  14. Diversity in olfactory bulb size in birds reflects allometry, ecology, and phylogeny

    PubMed Central

    Corfield, Jeremy R.; Price, Kasandra; Iwaniuk, Andrew N.; Gutierrez-Ibañez, Cristian; Birkhead, Tim; Wylie, Douglas R.

    2015-01-01

    The relative size of olfactory bulbs (OBs) is correlated with olfactory capabilities across vertebrates and is widely used to assess the relative importance of olfaction to a species’ ecology. In birds, variations in the relative size of OBs are correlated with some behaviors; however, the factors that have led to the high level of diversity seen in OB sizes across birds are still not well understood. In this study, we use the relative size of OBs as a neuroanatomical proxy for olfactory capabilities in 135 species of birds, representing 21 orders. We examine the scaling of OBs with brain size across avian orders, determine likely ancestral states and test for correlations between OB sizes and habitat, ecology, and behavior. The size of avian OBs varied with the size of the brain and this allometric relationship was for the most part isometric, although species did deviate from this trend. Large OBs were characteristic of more basal species and in more recently derived species the OBs were small. Living and foraging in a semi-aquatic environment was the strongest variable driving the evolution of large OBs in birds; olfaction may provide cues for navigation and foraging in this otherwise featureless environment. Some of the diversity in OB sizes was also undoubtedly due to differences in migratory behavior, foraging strategies and social structure. In summary, relative OB size in birds reflect allometry, phylogeny and behavior in ways that parallel that of other vertebrate classes. This provides comparative evidence that supports recent experimental studies into avian olfaction and suggests that olfaction is an important sensory modality for all avian species. PMID:26283931

  15. Reduction of Glucose Metabolism in Olfactory Bulb is an Earlier Alzheimer's Disease-related Biomarker in 5XFAD Mice

    PubMed Central

    Xiao, Nai-An; Zhang, Jing; Zhou, Meng; Wei, Zhen; Wu, Xi-Lin; Dai, Xiao-Man; Zhu, Yuan-Gui; Chen, Xiao-Chun

    2015-01-01

    Background: Early diagnosis assumes a vital role in an effective treatment of Alzheimer's disease (AD). Most of the current studies can only make an AD diagnosis after the manifestation of typical clinical symptoms. The present study aimed to investigate typical and other biomarkers of AD to find a possible early biomarker. Methods: A total of 14 5XFAD mice (at 3 and 6 months old), with 14 age-matched wild-type (WT) mice as control, were enrolled in this case-control study. Morris water maze test was performed to evaluate the cognitive function; buried food pellet test and olfactory maze test were employed to investigate the olfactory function; immunofluorescence to detect amyloid deposition and positron emission tomography to examine 2-deoxy-2-(18 F) fluoro-D-glucose ([18 F]-FDG) uptake in the hippocampus and cerebral cortex. Results: With the increasing age, cognitive performance (P = 0.0262) and olfactory function were significantly deteriorated (day 1 P = 0.0012, day 2 P = 0.0031, day 3 P = 0.0160, respectively) and the (18 F)-FDG uptake was markedly decreased in multi-cerebral regions including the olfactory bulb (P < 0.0001), hippocampus (P = 0.0121), and cerebral cortex (P < 0.0001). Of note, in 3-month-old 5XFAD mice, a significant decline of (18 F)-FDG uptake in the olfactory bulb was found when compared with that of age-matched WT mice (P = 0.023) while no significant difference was present when the uptakes in other cerebral regions were compared. Conclusions: The decline of (18 F)-FDG uptake in the olfactory bulb occurs earlier than other incidents, serving as an earlier in vivo biological marker of AD in 5XFAD mice and making early diagnosis of AD possibly. PMID:26265617

  16. A novel bioelectronic nose based on brain-machine interface using implanted electrode recording in vivo in olfactory bulb.

    PubMed

    Dong, Qi; Du, Liping; Zhuang, Liujing; Li, Rong; Liu, Qingjun; Wang, Ping

    2013-11-15

    The mammalian olfactory system has merits of higher sensitivity, selectivity and faster response than current electronic nose system based on chemical sensor array. It is advanced and feasible to detect and discriminate odors by mammalian olfactory system. The purpose of this study is to develop a novel bioelectronic nose based on the brain-machine interface (BMI) technology for odor detection by in vivo electrophysiological measurements of olfactory bulb. In this work, extracellular potentials of mitral/tufted (M/T) cells in olfactory bulb (OB) were recorded by implanted 16-channel microwire electrode arrays. The odor-evoked response signals were analyzed. We found that neural activities of different neurons showed visible different firing patterns both in temporal features and rate features when stimulated by different small molecular odorants. The detection low limit is below 1 ppm for some specific odors. Odors were classified by an algorithm based on population vector similarity and support vector machine (SVM). The results suggested that the novel bioelectonic nose was sensitive to odorant stimuli. The best classifying accuracy was up to 95%. With the development of the BMI and olfactory decoding methods, we believe that this system will represent emerging and promising platforms for wide applications in medical diagnosis and security fields.

  17. Staging of alpha-synuclein in the olfactory bulb in a model of Parkinson's disease: cell types involved.

    PubMed

    Ubeda-Bañon, Isabel; Saiz-Sanchez, Daniel; de la Rosa-Prieto, Carlos; Mohedano-Moriano, Alicia; Fradejas, Noelia; Calvo, Soledad; Argandoña-Palacios, Lucia; Garcia-Muñozguren, Susana; Martinez-Marcos, Alino

    2010-08-15

    Impaired olfaction is an early symptom of Parkinson's disease. The underlying neuropathology likely includes alpha-synucleinopathy in the olfactory bulb at an earlier stage (Braak's stage1) than pathology in the substantia nigra, which is not observed until stage 3. In this report, we investigated the distribution and cell types affected by alpha-synuclein in the olfactory bulb of transgenic mice (2-8 months of age) expressing the human A53T variant of alpha-synuclein. alpha-Synuclein immunostaining progressively affects interneurons and mitral cells. Double labeling studies demonstrate that dopaminergic cells are hardly involved, whereas glutamatergic- and calcium binding protein-positive cells are severely affected. This temporal evolution and the cell types expressing alpha-synuclein are reminiscent of idiopathic Parkinson's disease and support the usefulness of this model to address specific topics in the premotor phase of the disease.

  18. Cellular and molecular cues of glucose sensing in the rat olfactory bulb

    PubMed Central

    Al Koborssy, Dolly; Palouzier-Paulignan, Brigitte; Salem, Rita; Thevenet, Marc; Romestaing, Caroline; Julliard, A. Karyn

    2014-01-01

    In the brain, glucose homeostasis of extracellular fluid is crucial to the point that systems specifically dedicated to glucose sensing are found in areas involved in energy regulation and feeding behavior. Olfaction is a major sensory modality regulating food consumption. Nutritional status in turn modulates olfactory detection. Recently it has been proposed that some olfactory bulb (OB) neurons respond to glucose similarly to hypothalamic neurons. However, the precise molecular cues governing glucose sensing in the OB are largely unknown. To decrypt these molecular mechanisms, we first used immunostaining to demonstrate a strong expression of two neuronal markers of glucose-sensitivity, insulin-dependent glucose transporter type 4 (GLUT4), and sodium glucose co-transporter type 1 (SGLT1) in specific OB layers. We showed that expression and mapping of GLUT4 but not SGLT1 were feeding state-dependent. In order to investigate the impact of metabolic status on the delivery of blood-borne glucose to the OB, we measured extracellular fluid glucose concentration using glucose biosensors simultaneously in the OB and cortex of anesthetized rats. We showed that glucose concentration in the OB is higher than in the cortex, that metabolic steady-state glucose concentration is independent of feeding state in the two brain areas, and that acute changes in glycemic conditions affect bulbar glucose concentration alone. These data provide new evidence of a direct relationship between the OB and peripheral metabolism, and emphasize the importance of glucose for the OB network, providing strong arguments toward establishing the OB as a glucose-sensing organ. PMID:25400540

  19. Odour enrichment increases adult-born dopaminergic neurons in the mouse olfactory bulb.

    PubMed

    Bonzano, Sara; Bovetti, Serena; Fasolo, Aldo; Peretto, Paolo; De Marchis, Silvia

    2014-11-01

    The olfactory bulb (OB) is the first brain region involved in the processing of olfactory information. In adult mice, the OB is highly plastic, undergoing cellular/molecular dynamic changes that are modulated by sensory experience. Odour deprivation induces down-regulation of tyrosine hydroxylase (TH) expression in OB dopaminergic interneurons located in the glomerular layer (GL), resulting in decreased dopamine in the OB. Although the effect of sensory deprivation is well established, little is known about the influence of odour enrichment on dopaminergic cells. Here we report that prolonged odour enrichment on C57BL/6J strain mice selectively increases TH-immunopositive cells in the GL by nearly 20%. Following odour enrichment on TH-green fluorescent protein (GFP) transgenic mice, in which GFP identified both mature TH-positive cells and putative immature dopaminergic cells expressing TH mRNA but not TH protein, we found a similar 20% increase in GFP-expressing cells, with no changes in the ratio between TH-positive and TH-negative cells. These data suggest that enriched conditions induce an expansion in the whole dopaminergic lineage. Accordingly, by using 5-bromo-2-deoxyuridine injections to label adult-generated cells in the GL of TH-GFP mice, we found an increase in the percentage of 5-bromo-2-deoxyuridine-positive dopaminergic cells in enriched compared with control conditions, whereas no differences were found for calretinin- and calbindin-positive subtypes. Strikingly, the fraction of newborn cells among the dopaminergic population doubled in enriched conditions. On the whole, our results demonstrate that odour enrichment drives increased integration of adult-generated dopaminergic cells that could be critical to adapt the OB circuits to the environmental incoming information.

  20. Glomerular and Mitral-Granule Cell Microcircuits Coordinate Temporal and Spatial Information Processing in the Olfactory Bulb

    PubMed Central

    Cavarretta, Francesco; Marasco, Addolorata; Hines, Michael L.; Shepherd, Gordon M.; Migliore, Michele

    2016-01-01

    The olfactory bulb processes inputs from olfactory receptor neurons (ORNs) through two levels: the glomerular layer at the site of input, and the granule cell level at the site of output to the olfactory cortex. The sequence of action of these two levels has not yet been examined. We analyze this issue using a novel computational framework that is scaled up, in three-dimensions (3D), with realistic representations of the interactions between layers, activated by simulated natural odors, and constrained by experimental and theoretical analyses. We suggest that the postulated functions of glomerular circuits have as their primary role transforming a complex and disorganized input into a contrast-enhanced and normalized representation, but cannot provide for synchronization of the distributed glomerular outputs. By contrast, at the granule cell layer, the dendrodendritic interactions mediate temporal decorrelation, which we show is dependent on the preceding contrast enhancement by the glomerular layer. The results provide the first insights into the successive operations in the olfactory bulb, and demonstrate the significance of the modular organization around glomeruli. This layered organization is especially important for natural odor inputs, because they activate many overlapping glomeruli. PMID:27471461

  1. Odor-elicited activity monitored simultaneously from 124 regions of the salamander olfactory bulb using a voltage-sensitive dye.

    PubMed

    Kauer, J S; Senseman, D M; Cohen, L B

    1987-08-25

    In response to controlled, odor pulse stimulation of the olfactory receptor mucosa, large fluorescence signals were recorded simultaneously from 124 contiguous anatomical regions of the salamander olfactory bulb using the potentiometric probe RH 414. The amplitudes and waveforms of the signals varied systematically across the bulbar surface in apparent correspondence with the laminae of the bulbar neurons. Qualitatively similar results were obtained using both intact and decorporate preparations, although fluorescence signals obtained from intact animals were distorted by optical noise generated by mechanical disturbances related to the functioning cardiovascular system. These results indicate that multiple site optical recording can be used to obtain information about spatio-temporal patterning of bulbar electrical activity evoked by physiological odor stimulation of the receptor mucosa. This is the first demonstration that activity elicited by a single, one second odor stimulus at physiological concentration and duration can be measured across many elements in the olfactory bulb. Information provided by this approach, in combination with complementary data derived from 2-deoxyglucose and single unit studies, may yield a better understanding of how the vertebrate central nervous system extracts quality and concentration information from olfactory afferent input.

  2. Synaptic connectivity of the cholinergic axons in the olfactory bulb of the cynomolgus monkey

    PubMed Central

    Liberia, Teresa; Blasco-Ibáñez, José Miguel; Nácher, Juan; Varea, Emilio; Lanciego, José Luis; Crespo, Carlos

    2015-01-01

    The olfactory bulb (OB) of mammals receives cholinergic afferents from the horizontal limb of the diagonal band of Broca (HDB). At present, the synaptic connectivity of the cholinergic axons on the circuits of the OB has only been investigated in the rat. In this report, we analyze the synaptic connectivity of the cholinergic axons in the OB of the cynomolgus monkey (Macaca fascicularis). Our aim is to investigate whether the cholinergic innervation of the bulbar circuits is phylogenetically conserved between macrosmatic and microsmatic mammals. Our results demonstrate that the cholinergic axons form synaptic contacts on interneurons. In the glomerular layer, their main targets are the periglomerular cells, which receive axo-somatic and axo-dendritic synapses. In the inframitral region, their main targets are the granule cells, which receive synaptic contacts on their dendritic shafts and spines. Although the cholinergic boutons were frequently found in close vicinity of the dendrites of principal cells, we have not found synaptic contacts on them. From a comparative perspective, our data indicate that the synaptic connectivity of the cholinergic circuits is highly preserved in the OB of macrosmatic and microsmatic mammals. PMID:25852490

  3. The Adult Ventricular-Subventricular Zone (V-SVZ) and Olfactory Bulb (OB) Neurogenesis.

    PubMed

    Lim, Daniel A; Alvarez-Buylla, Arturo

    2016-05-02

    A large population of neural stem/precursor cells (NSCs) persists in the ventricular-subventricular zone (V-SVZ) located in the walls of the lateral brain ventricles. V-SVZ NSCs produce large numbers of neuroblasts that migrate a long distance into the olfactory bulb (OB) where they differentiate into local circuit interneurons. Here, we review a broad range of discoveries that have emerged from studies of postnatal V-SVZ neurogenesis: the identification of NSCs as a subpopulation of astroglial cells, the neurogenic lineage, new mechanisms of neuronal migration, and molecular regulators of precursor cell proliferation and migration. It has also become evident that V-SVZ NSCs are regionally heterogeneous, with NSCs located in different regions of the ventricle wall generating distinct OB interneuron subtypes. Insights into the developmental origins and molecular mechanisms that underlie the regional specification of V-SVZ NSCs have also begun to emerge. Other recent studies have revealed new cell-intrinsic molecular mechanisms that enable lifelong neurogenesis in the V-SVZ. Finally, we discuss intriguing differences between the rodent V-SVZ and the corresponding human brain region. The rapidly expanding cellular and molecular knowledge of V-SVZ NSC biology provides key insights into postnatal neural development, the origin of brain tumors, and may inform the development regenerative therapies from cultured and endogenous human neural precursors.

  4. Increased olfactory bulb acetylcholine bi-directionally modulates glomerular odor sensitivity

    PubMed Central

    Bendahmane, Mounir; Ogg, M. Cameron; Ennis, Matthew; Fletcher, Max L.

    2016-01-01

    The glomerular layer of the olfactory bulb (OB) receives heavy cholinergic input from the horizontal limb of the diagonal band of Broca (HDB) and expresses both muscarinic and nicotinic acetylcholine (ACh) receptors. However, the effects of ACh on OB glomerular odor responses remain unknown. Using calcium imaging in transgenic mice expressing the calcium indicator GCaMP2 in the mitral/tufted cells, we investigated the effect of ACh on the glomerular responses to increasing odor concentrations. Using HDB electrical stimulation and in vivo pharmacology, we find that increased OB ACh leads to dynamic, activity-dependent bi-directional modulation of glomerular odor response due to the combinatorial effects of both muscarinic and nicotinic activation. Using pharmacological manipulation to reveal the individual receptor type contributions, we find that m2 muscarinic receptor activation increases glomerular sensitivity to weak odor input whereas nicotinic receptor activation decreases sensitivity to strong input. Overall, we found that ACh in the OB increases glomerular sensitivity to odors and decreases activation thresholds. This effect, along with the decreased responses to strong odor input, reduces the response intensity range of individual glomeruli to increasing concentration making them more similar across the entire concentration range. As a result, odor representations are more similar as concentration increases. PMID:27165547

  5. Prolonged Intracellular Na+ Dynamics Govern Electrical Activity in Accessory Olfactory Bulb Mitral Cells.

    PubMed

    Zylbertal, Asaph; Kahan, Anat; Ben-Shaul, Yoram; Yarom, Yosef; Wagner, Shlomo

    2015-12-01

    Persistent activity has been reported in many brain areas and is hypothesized to mediate working memory and emotional brain states and to rely upon network or biophysical feedback. Here, we demonstrate a novel mechanism by which persistent neuronal activity can be generated without feedback, relying instead on the slow removal of Na+ from neurons following bursts of activity. We show that mitral cells in the accessory olfactory bulb (AOB), which plays a major role in mammalian social behavior, may respond to a brief sensory stimulation with persistent firing. By combining electrical recordings, Ca2+ and Na+ imaging, and realistic computational modeling, we explored the mechanisms underlying the persistent activity in AOB mitral cells. We found that the exceptionally slow inward current that underlies this activity is governed by prolonged dynamics of intracellular Na+ ([Na+]i), which affects neuronal electrical activity via several pathways. Specifically, elevated dendritic [Na+]i reverses the Na+-Ca2+ exchanger activity, thus modifying the [Ca2+]i set-point. This process, which relies on ubiquitous membrane mechanisms, is likely to play a role in other neuronal types in various brain regions. PMID:26674618

  6. Reelin together with ApoER2 regulates interneuron migration in the olfactory bulb.

    PubMed

    Hellwig, Sabine; Hack, Iris; Zucker, Birgit; Brunne, Bianka; Junghans, Dirk

    2012-01-01

    One pathway regulating the migration of neurons during development of the mammalian cortex involves the extracellular matrix protein Reelin. Reelin and components of its signaling cascade, the lipoprotein receptors ApoER2 and Vldlr and the intracellular adapter protein Dab1 are pivotal for a correct layer formation during corticogenesis. The olfactory bulb (OB) as a phylogenetically old cortical region is known to be a prominent site of Reelin expression. Although some aspects of Reelin function in the OB have been described, the influence of Reelin on OB layer formation has so far been poorly analyzed. Here we studied animals deficient for either Reelin, Vldlr, ApoER2 or Dab1 as well as double-null mutants. We performed organotypic migration assays, immunohistochemical marker analysis and BrdU incorporation studies to elucidate roles for the different components of the Reelin signaling cascade in OB neuroblast migration and layer formation. We identified ApoER2 as being the main receptor responsible for Reelin mediated detachment of neuroblasts and correct migration of early generated interneurons within the OB, a prerequisite for correct OB lamination.

  7. Chronic Spinal Injury Repair by Olfactory Bulb Ensheathing Glia and Feasibility for Autologous Therapy

    PubMed Central

    Muñoz-Quiles, Cintia; Santos-Benito, Fernando F.; Llamusí, M. Beatriz; Ramón-Cueto, Almudena

    2009-01-01

    Olfactory bulb ensheathing glia (OB-OEG) promote repair of spinal cord injury (SCI) in rats after transplantation at acute or subacute (up to 45 days) stages. The most relevant clinical scenario in humans, however, is chronic SCI, in which no more major cellular or molecular changes occur at the injury site; this occurs after the third month in rodents. Whether adult OB-OEG grafts promote repair of severe chronic SCI has not been previously addressed. Rats with complete SCI that were transplanted with OB-OEG 4 months after injury exhibited progressive improvement in motor function and axonal regeneration from different brainstem nuclei across and beyond the SCI site. A positive correlation between motor outcome and axonal regeneration suggested a role for brainstem neurons in the recovery. Functional and histological outcomes did not differ at subacute or chronic stages. Thus, autologous transplantation is a feasible approach as there is time for patient stabilization and OEG preparation in human chronic SCI; the healing effects of OB-OEG on established injuries may offer new therapeutic opportunities for chronic SCI patients. PMID:19915486

  8. Lgl1 Is Required for Olfaction and Development of Olfactory Bulb in Mice

    PubMed Central

    Li, Zhenzu; Zhang, Tingting; Lin, Zhuchun; Hou, Congzhe; Zhang, Jian; Men, Yuqin; Li, Huashun

    2016-01-01

    Lethal giant larvae 1 (Lgl1) was initially identified as a tumor suppressor in Drosophila and functioned as a key regulator of epithelial polarity and asymmetric cell division. In this study, we generated Lgl1 conditional knockout mice mediated by Pax2-Cre, which is expressed in olfactory bulb (OB). Next, we examined the effects of Lgl1 loss in the OB. First, we determined the expression patterns of Lgl1 in the neurogenic regions of the embryonic dorsal region of the LGE (dLGE) and postnatal OB. Furthermore, the Lgl1 conditional mutants exhibited abnormal morphological characteristics of the OB. Our behavioral analysis exhibited greatly impaired olfaction in Lgl1 mutant mice. To elucidate the possible mechanisms of impaired olfaction in Lgl1 mutant mice, we investigated the development of the OB. Interestingly, reduced thickness of the MCL and decreased density of mitral cells (MCs) were observed in Lgl1 mutant mice. Additionally, we observed a dramatic loss in SP8+ interneurons (e.g. calretinin and GABAergic/non-dopaminergic interneurons) in the GL of the OB. Our results demonstrate that Lgl1 is required for the development of the OB and the deletion of Lgl1 results in impaired olfaction in mice. PMID:27603780

  9. The Role of Adult-Born Neurons in the Constantly Changing Olfactory Bulb Network

    PubMed Central

    Malvaut, Sarah; Saghatelyan, Armen

    2016-01-01

    The adult mammalian brain is remarkably plastic and constantly undergoes structurofunctional modifications in response to environmental stimuli. In many regions plasticity is manifested by modifications in the efficacy of existing synaptic connections or synapse formation and elimination. In a few regions, however, plasticity is brought by the addition of new neurons that integrate into established neuronal networks. This type of neuronal plasticity is particularly prominent in the olfactory bulb (OB) where thousands of neuronal progenitors are produced on a daily basis in the subventricular zone (SVZ) and migrate along the rostral migratory stream (RMS) towards the OB. In the OB, these neuronal precursors differentiate into local interneurons, mature, and functionally integrate into the bulbar network by establishing output synapses with principal neurons. Despite continuous progress, it is still not well understood how normal functioning of the OB is preserved in the constantly remodelling bulbar network and what role adult-born neurons play in odor behaviour. In this review we will discuss different levels of morphofunctional plasticity effected by adult-born neurons and their functional role in the adult OB and also highlight the possibility that different subpopulations of adult-born cells may fulfill distinct functions in the OB neuronal network and odor behaviour. PMID:26839709

  10. Morphological analysis of activity-reduced adult-born neurons in the mouse olfactory bulb.

    PubMed

    Dahlen, Jeffrey E; Jimenez, Daniel A; Gerkin, Richard C; Urban, Nathan N

    2011-01-01

    Adult-born neurons (ABNs) are added to the olfactory bulb (OB) throughout life in rodents. While many factors have been identified as regulating the survival and integration of ABNs into existing circuitry, the understanding of how these factors affect ABN morphology and connectivity is limited. Here we compare how cell intrinsic [small interfering RNA (siRNA) knock-down of voltage gated sodium channels Na(V)1.1-1.3] and circuit level (naris occlusion) reductions in activity affect ABN morphology during integration into the OB. We found that both manipulations reduce the number of dendritic spines (and thus likely the number of reciprocal synaptic connections) formed with the surrounding circuitry and inhibited dendritic ramification of ABNs. Further, we identified regions of ABN apical dendrites where the largest and most significant decreases occur following siRNA knock-down or naris occlusion. In siRNA knock-down cells, reduction of spines is observed in proximal regions of the apical dendrite. This suggests that distal regions of the dendrite may remain active independent of Na(V)1.1-1.3 channel expression, perhaps facilitated by activation of T-type calcium channels and NMDA receptors. By contrast, circuit level reduction of activity by naris occlusion resulted in a global depression of spine number. Together, these results indicate that ABNs retain the ability to develop their typical overall morphological features regardless of experienced activity, and activity modulates the number and location of formed connections.

  11. Functional optical coherence tomography of rat olfactory bulb with periodic odor stimulation

    PubMed Central

    Watanabe, Hideyuki; Rajagopalan, Uma Maheswari; Nakamichi, Yu; Igarashi, Kei M.; Kadono, Hirofumi; Tanifuji, Manabu

    2016-01-01

    In rodent olfactory bulb (OB), optical intrinsic signal imaging (OISI) is commonly used to investigate functional maps to odorant stimulations. However, in such studies, the spatial resolution in depth direction (z-axis) is lost because of the integration of light from different depths. To solve this problem, we propose functional optical coherence tomography (fOCT) with periodic stimulation and continuous recording. In fOCT experiments of in vivo rat OB, propionic acid and m-cresol were used as odor stimulus presentations. Such a periodic stimulation enabled us to detect the specific odor-responses from highly scattering brain tissue. Swept source OCT operating at a wavelength of 1334 nm and a frequency of 20 kHz, was employed with theoretical depth and lateral resolutions of 6.7 μm and 15.4 μm, respectively. We succeeded in visualizing 2D cross sectional fOCT map across the neural layer structure of OCT in vivo. The detected fOCT signals corresponded to a few glomeruli of the medial and lateral parts of dorsal OB. We also obtained 3D fOCT maps, which upon integration across z-axis agreed well with OISI results. We expect such an approach to open a window for investigating and possibly addressing toward inter/intra-layer connections at high resolutions in the future. PMID:27231593

  12. Migration of neuronal precursors from the telencephalic ventricular zone into the olfactory bulb in adult zebrafish.

    PubMed

    Kishimoto, Norihito; Alfaro-Cervello, Clara; Shimizu, Kohei; Asakawa, Kazuhide; Urasaki, Akihiro; Nonaka, Shigenori; Kawakami, Koichi; Garcia-Verdugo, Jose Manuel; Sawamoto, Kazunobu

    2011-12-01

    In the brain of adult mammals, neuronal precursors are generated in the subventricular zone in the lateral wall of the lateral ventricles and migrate into the olfactory bulbs (OBs) through a well-studied route called the rostral migratory stream (RMS). Recent studies have revealed that a comparable neural stem cell niche is widely conserved at the ventricular wall of adult vertebrates. However, little is known about the migration route of neuronal precursors in nonmammalian adult brains. Here, we show that, in the adult zebrafish, a cluster of neuronal precursors generated in the telencephalic ventricular zone migrates into the OB via a route equivalent to the mammalian RMS. Unlike the mammalian RMS, these neuronal precursors are not surrounded by glial tubes, although radial glial cells with a single cilium lined the telencephalic ventricular wall, much as in embryonic and neonatal mammals. To observe the migrating neuronal precursors in living brain tissue, we established a brain hemisphere culture using a zebrafish line carrying a GFP transgene driven by the neurogenin1 (ngn1) promoter. In these fish, GFP was observed in the neuronal precursors migrating in the RMS, some of which were aligned with blood vessels. Numerous ngn1:gfp-positive cells were observed migrating tangentially in the RMS-like route medial to the OB. Taken together, our results suggest that the RMS in the adult zebrafish telencephalon is a functional migratory pathway. This is the first evidence for the tangential migration of neuronal precursors in a nonmammalian adult telencephalon.

  13. Role of the Retinoblastoma protein, Rb, during adult neurogenesis in the olfactory bulb

    PubMed Central

    Naser, Rayan; Vandenbosch, Renaud; Omais, Saad; Hayek, Dayana; Jaafar, Carine; Al Lafi, Sawsan; Saliba, Afaf; Baghdadi, Maarouf; Skaf, Larissa; Ghanem, Noël

    2016-01-01

    Adult neural stem cells (aNSCs) are relatively quiescent populations that give rise to distinct neuronal subtypes throughout life, yet, at a very low rate and restricted differentiation potential. Thus, identifying the molecular mechanisms that control their cellular expansion is critical for regeneration after brain injury. Loss of the Retinoblastoma protein, Rb, leads to several defects in cell cycle as well as neuronal differentiation and migration during brain development. Here, we investigated the role of Rb during adult neurogenesis in the olfactory bulb (OB) by inducing its temporal deletion in aNSCs and progenitors. Loss of Rb was associated with increased proliferation of adult progenitors in the subventricular zone (SVZ) and the rostral migratory stream (RMS) but did not alter self-renewal of aNSCs or neuroblasts subsequent migration and terminal differentiation. Hence, one month after their birth, Rb-null neuroblasts were able to differentiate into distinct subtypes of GABAergic OB interneurons but were gradually lost after 3 months. Similarly, Rb controlled aNSCs/progenitors proliferation in vitro without affecting their differentiation capacity. This enhanced SVZ/OB neurogenesis associated with loss of Rb was only transient and negatively affected by increased apoptosis indicating a critical requirement for Rb in the long-term survival of adult-born OB interneurons. PMID:26847607

  14. Brain-state dependent uncoupling of BOLD and local field potentials in laminar olfactory bulb.

    PubMed

    Gong, Ling; Li, Bo; Wu, Ruiqi; Li, Anan; Xu, Fuqiang

    2014-09-19

    The neural activities of the olfactory bulb (OB) can be modulated significantly by internal brain states. While blood oxygenation level dependent functional MRI (BOLD-fMRI) has been extensively applied to study OB in small animals, the relationship between BOLD signals and electrophysiological signals remains to be elucidated. Our recent study has revealed a complex relationship between BOLD and local field potentials (LFP) signals in different OB layers during odor stimulation. However, no study has been performed to compare these two types of signals under global brain states. Here, the changes of BOLD and LFP signals in the glomerular, mitral cell, and granular cell layers of the OB under different brain states, which were induced by different concentrations of isoflurane, were sequentially acquired using electrode array and high-resolution MRI. It was found that under deeper anesthesia, the LFP powers in all layers were decreased but the BOLD signals were unexpectedly increased. Furthermore, the decreases of LFP powers were layer-independent, but the increases of BOLD signal were layer-specific, with the order of glomerular>mitral cell>granular cell layer. The results provide new evidence that the direct neural activity levels might not be correlated well with BOLD signals in some cases, and remind us that cautions should be taken to use BOLD signals as the index of neural activities.

  15. Complex relationship between BOLD-fMRI and electrophysiological signals in different olfactory bulb layers.

    PubMed

    Li, Bo; Gong, Ling; Wu, Ruiqi; Li, Anan; Xu, Fuqiang

    2014-07-15

    Blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI), one of the most powerful technologies in neuroscience, measures neural activity indirectly. Therefore, systematic correlation of BOLD signals with other neural activity measurements is critical to understanding and then using the technology. Numerous studies have revealed that the BOLD signal is determined by many factors and is better correlated with local field potentials (LFP) than single/multiple unit firing. The relationship between BOLD and LFP signals under higher spatial resolution is complex and remains unclear. Here, changes of BOLD and LFP signals in the glomerular (GL), mitral cell (MCL), and granular cell layers (GCL) of the olfactory bulb were evoked by odor stimulation and sequentially acquired using high-resolution fMRI and electrode array. The experimental results revealed a rather complex relationship between BOLD and LFP signals. Both signal modalities were increased layer-dependently by odor stimulation, but the orders of signal intensity were significantly different: GL>MCL>GCL and GCL>GL>MCL for BOLD and LFP, respectively. During odor stimulation, the temporal features of LFPs were similar for a given band in different layers, but different for different frequency bands in a given layer. The BOLD and LFP signals in the low gamma frequency band correlated the best. This study provides new evidence for the consistency between structure and function in understanding the neurophysiological basis of BOLD signals, but also reminds that caution must be taken in interpreting of BOLD signals in regard to neural activity.

  16. Prolonged Intracellular Na+ Dynamics Govern Electrical Activity in Accessory Olfactory Bulb Mitral Cells.

    PubMed

    Zylbertal, Asaph; Kahan, Anat; Ben-Shaul, Yoram; Yarom, Yosef; Wagner, Shlomo

    2015-12-01

    Persistent activity has been reported in many brain areas and is hypothesized to mediate working memory and emotional brain states and to rely upon network or biophysical feedback. Here, we demonstrate a novel mechanism by which persistent neuronal activity can be generated without feedback, relying instead on the slow removal of Na+ from neurons following bursts of activity. We show that mitral cells in the accessory olfactory bulb (AOB), which plays a major role in mammalian social behavior, may respond to a brief sensory stimulation with persistent firing. By combining electrical recordings, Ca2+ and Na+ imaging, and realistic computational modeling, we explored the mechanisms underlying the persistent activity in AOB mitral cells. We found that the exceptionally slow inward current that underlies this activity is governed by prolonged dynamics of intracellular Na+ ([Na+]i), which affects neuronal electrical activity via several pathways. Specifically, elevated dendritic [Na+]i reverses the Na+-Ca2+ exchanger activity, thus modifying the [Ca2+]i set-point. This process, which relies on ubiquitous membrane mechanisms, is likely to play a role in other neuronal types in various brain regions.

  17. Persistent Structural Plasticity Optimizes Sensory Information Processing in the Olfactory Bulb.

    PubMed

    Sailor, Kurt A; Valley, Matthew T; Wiechert, Martin T; Riecke, Hermann; Sun, Gerald J; Adams, Wayne; Dennis, James C; Sharafi, Shirin; Ming, Guo-Li; Song, Hongjun; Lledo, Pierre-Marie

    2016-07-20

    In the mammalian brain, the anatomical structure of neural circuits changes little during adulthood. As a result, adult learning and memory are thought to result from specific changes in synaptic strength. A possible exception is the olfactory bulb (OB), where activity guides interneuron turnover throughout adulthood. These adult-born granule cell (GC) interneurons form new GABAergic synapses that have little synaptic strength plasticity. In the face of persistent neuronal and synaptic turnover, how does the OB balance flexibility, as is required for adapting to changing sensory environments, with perceptual stability? Here we show that high dendritic spine turnover is a universal feature of GCs, regardless of their developmental origin and age. We find matching dynamics among postsynaptic sites on the principal neurons receiving the new synaptic inputs. We further demonstrate in silico that this coordinated structural plasticity is consistent with stable, yet flexible, decorrelated sensory representations. Together, our study reveals that persistent, coordinated synaptic structural plasticity between interneurons and principal neurons is a major mode of functional plasticity in the OB. PMID:27373833

  18. New insights into the role of histamine in subventricular zone-olfactory bulb neurogenesis

    PubMed Central

    Eiriz, Maria F.; Valero, Jorge; Malva, João O.; Bernardino, Liliana

    2014-01-01

    The subventricular zone (SVZ) contains neural stem cells (NSCs) that generate new neurons throughout life. Many brain diseases stimulate NSCs proliferation, neuronal differentiation and homing of these newborns cells into damaged regions. However, complete cell replacement has never been fully achieved. Hence, the identification of proneurogenic factors crucial for stem cell-based therapies will have an impact in brain repair. Histamine, a neurotransmitter and immune mediator, has been recently described to modulate proliferation and commitment of NSCs. Histamine levels are increased in the brain parenchyma and at the cerebrospinal fluid (CSF) upon inflammation and brain injury, thus being able to modulate neurogenesis. Herein, we add new data showing that in vivo administration of histamine in the lateral ventricles has a potent proneurogenic effect, increasing the production of new neuroblasts in the SVZ that ultimately reach the olfactory bulb (OB). This report emphasizes the multidimensional effects of histamine in the modulation of NSCs dynamics and sheds light into the promising therapeutic role of histamine for brain regenerative medicine. PMID:24982610

  19. Age-Dependent Neurogenesis and Neuron Numbers within the Olfactory Bulb and Hippocampus of Homing Pigeons

    PubMed Central

    Meskenaite, Virginia; Krackow, Sven; Lipp, Hans-Peter

    2016-01-01

    Many birds are supreme long-distance navigators that develop their navigational ability in the first months after fledgling but update the memorized environmental information needed for navigation also later in life. We studied the extent of juvenile and adult neurogenesis that could provide such age-related plasticity in brain regions known to mediate different mechanisms of pigeon homing: the olfactory bulb (OB), and the triangular area of the hippocampal formation (HP tr). Newly generated neurons (visualized by doublecortin, DCX) and mature neurons were counted stereologically in 35 pigeon brains ranging from 1 to 168 months of age. At the age of 1 month, both areas showed maximal proportions of DCX positive neurons, which rapidly declined during the first year of life. In the OB, the number of DCX-positive periglomerular neurons declined further over time, but the number of mature periglomerular cells appeared unchanged. In the hippocampus, the proportion of DCX-positive neurons showed a similar decline yet to a lesser extent. Remarkably, in the triangular area of the hippocampus, the oldest birds showed nearly twice the number of neurons as compared to young adult pigeons, suggesting that adult born neurons in these regions expanded the local circuitry even in aged birds. This increase might reflect navigational experience and, possibly, expanded spatial memory. On the other hand, the decrease of juvenile neurons in the aging OB without adding new circuitry might be related to the improved attachment to the loft characterizing adult and old pigeons. PMID:27445724

  20. Sodium current in periglomerular cells of frog olfactory bulb in vitro.

    PubMed

    Bardoni, R; Magherini, P C; Belluzzi, O

    1995-12-12

    Kinetic properties of the sodium current in periglomerular (PG) cells were investigated by applying whole-cell patch-clamp techniques to thin slices of the frog olfactory bulb. Eight of the cells were intracellularly stained with Lucifer Yellow for precise identification. Under current-clamp conditions PG cells showed rich spontaneous activity at rest. Na current was isolated from other current contributions by equimolar substitution of K+ with Cs+ in the intracellular solution to prevent K-currents, and 100 microM Cd2+ in the external solution to block Ca-current. Depolarisations beyond -40 mV activated a fast transient TTX-sensitive inward current. Once activated, INa declined exponentially to zero following a single exponential. The underlying conductance showed a sigmoidal activation between -40 and +30 mV, with half activation at -17.4 mV and a maximal value of 9.7 nS per neurone. The steady-state inactivation was complete at -30 mV and completely removed at -90 mV, with a midpoint at -56 mV. The activation process could be adequately described by third order kinetics, with time constants ranging from 260 microseconds at -20 mV to 70 microseconds at +50 mV.

  1. Lgl1 Is Required for Olfaction and Development of Olfactory Bulb in Mice.

    PubMed

    Li, Zhenzu; Zhang, Tingting; Lin, Zhuchun; Hou, Congzhe; Zhang, Jian; Men, Yuqin; Li, Huashun; Gao, Jiangang

    2016-01-01

    Lethal giant larvae 1 (Lgl1) was initially identified as a tumor suppressor in Drosophila and functioned as a key regulator of epithelial polarity and asymmetric cell division. In this study, we generated Lgl1 conditional knockout mice mediated by Pax2-Cre, which is expressed in olfactory bulb (OB). Next, we examined the effects of Lgl1 loss in the OB. First, we determined the expression patterns of Lgl1 in the neurogenic regions of the embryonic dorsal region of the LGE (dLGE) and postnatal OB. Furthermore, the Lgl1 conditional mutants exhibited abnormal morphological characteristics of the OB. Our behavioral analysis exhibited greatly impaired olfaction in Lgl1 mutant mice. To elucidate the possible mechanisms of impaired olfaction in Lgl1 mutant mice, we investigated the development of the OB. Interestingly, reduced thickness of the MCL and decreased density of mitral cells (MCs) were observed in Lgl1 mutant mice. Additionally, we observed a dramatic loss in SP8+ interneurons (e.g. calretinin and GABAergic/non-dopaminergic interneurons) in the GL of the OB. Our results demonstrate that Lgl1 is required for the development of the OB and the deletion of Lgl1 results in impaired olfaction in mice. PMID:27603780

  2. Prolonged Intracellular Na+ Dynamics Govern Electrical Activity in Accessory Olfactory Bulb Mitral Cells

    PubMed Central

    Zylbertal, Asaph; Kahan, Anat; Ben-Shaul, Yoram; Yarom, Yosef; Wagner, Shlomo

    2015-01-01

    Persistent activity has been reported in many brain areas and is hypothesized to mediate working memory and emotional brain states and to rely upon network or biophysical feedback. Here, we demonstrate a novel mechanism by which persistent neuronal activity can be generated without feedback, relying instead on the slow removal of Na+ from neurons following bursts of activity. We show that mitral cells in the accessory olfactory bulb (AOB), which plays a major role in mammalian social behavior, may respond to a brief sensory stimulation with persistent firing. By combining electrical recordings, Ca2+ and Na+ imaging, and realistic computational modeling, we explored the mechanisms underlying the persistent activity in AOB mitral cells. We found that the exceptionally slow inward current that underlies this activity is governed by prolonged dynamics of intracellular Na+ ([Na+]i), which affects neuronal electrical activity via several pathways. Specifically, elevated dendritic [Na+]i reverses the Na+-Ca2+ exchanger activity, thus modifying the [Ca2+]i set-point. This process, which relies on ubiquitous membrane mechanisms, is likely to play a role in other neuronal types in various brain regions. PMID:26674618

  3. Bicuculline induces synapse formation on primary cultured accessory olfactory bulb neurons.

    PubMed

    Kato-Negishi, Midori; Muramoto, Kazuyo; Kawahara, Masahiro; Hosoda, Ritsuko; Kuroda, Yoichiro; Ichikawa, Masumi

    2003-09-01

    To investigate the roles of the GABAergic inhibitory system of accessory olfactory bulb (AOB) in pheromonal memory formation, we have developed a primary culture system of AOB neurons, which had numerous excitatory and inhibitory synapses. Using this culture system of AOB neurons, we examined the correlation in rats between neuronal excitation and synaptic morphology by bicuculline-induced disinhibition of cultured AOB neurons. The exposure to bicuculline induced long-lasting oscillatory changes in the intracellular calcium level ([Ca2+]in) of cultured non-GABAergic multipolar neurons, which were identified as mitral/tufted cells (MT cells). These MT cells exhibited the appearance of dendritic filopodia structures after a 10-min treatment with bicuculline. By labelling presynaptic terminals with FM4-64, the appearance of new presynaptic terminals was clearly observed on newly formed filopodia after 120 min treatment with bicuculline. These results suggest that bicuculline-induced [Ca2+]in oscillation of MT cells induces the growth of filopodia and subsequently the formation of new presynaptic terminals. Furthermore, tetrodotoxin or the deprivation of extracellular calcium blocked bicuculline-induced synapse formation. The present results indicate that the long-lasting [Ca2+]in oscillation caused by bicuculline-induced disinhibition of cultured MT cells is significantly implicated in the mechanism underlying synapse formation on cultured AOB neurons. Our established culture system of AOB neurons will aid in clarifying the mechanism of synapse formation between AOB neurons and the molecular mechanism of pheromonal memory formation. PMID:14511315

  4. Principal cell activity induces spine relocation of adult-born interneurons in the olfactory bulb

    PubMed Central

    Breton-Provencher, Vincent; Bakhshetyan, Karen; Hardy, Delphine; Bammann, Rodrigo Roberto; Cavarretta, Francesco; Snapyan, Marina; Côté, Daniel; Migliore, Michele; Saghatelyan, Armen

    2016-01-01

    Adult-born neurons adjust olfactory bulb (OB) network functioning in response to changing environmental conditions by the formation, retraction and/or stabilization of new synaptic contacts. While some changes in the odour environment are rapid, the synaptogenesis of adult-born neurons occurs over a longer time scale. It remains unknown how the bulbar network functions when rapid and persistent changes in environmental conditions occur but when new synapses have not been formed. Here we reveal a new form of structural remodelling where mature spines of adult-born but not early-born neurons relocate in an activity-dependent manner. Principal cell activity induces directional growth of spine head filopodia (SHF) followed by spine relocation. Principal cell-derived glutamate and BDNF regulate SHF motility and directional spine relocation, respectively; and spines with SHF are selectively preserved following sensory deprivation. Our three-dimensional model suggests that spine relocation allows fast reorganization of OB network with functional consequences for odour information processing. PMID:27578235

  5. Principal cell activity induces spine relocation of adult-born interneurons in the olfactory bulb.

    PubMed

    Breton-Provencher, Vincent; Bakhshetyan, Karen; Hardy, Delphine; Bammann, Rodrigo Roberto; Cavarretta, Francesco; Snapyan, Marina; Côté, Daniel; Migliore, Michele; Saghatelyan, Armen

    2016-01-01

    Adult-born neurons adjust olfactory bulb (OB) network functioning in response to changing environmental conditions by the formation, retraction and/or stabilization of new synaptic contacts. While some changes in the odour environment are rapid, the synaptogenesis of adult-born neurons occurs over a longer time scale. It remains unknown how the bulbar network functions when rapid and persistent changes in environmental conditions occur but when new synapses have not been formed. Here we reveal a new form of structural remodelling where mature spines of adult-born but not early-born neurons relocate in an activity-dependent manner. Principal cell activity induces directional growth of spine head filopodia (SHF) followed by spine relocation. Principal cell-derived glutamate and BDNF regulate SHF motility and directional spine relocation, respectively; and spines with SHF are selectively preserved following sensory deprivation. Our three-dimensional model suggests that spine relocation allows fast reorganization of OB network with functional consequences for odour information processing. PMID:27578235

  6. Functional optical coherence tomography of rat olfactory bulb with periodic odor stimulation.

    PubMed

    Watanabe, Hideyuki; Rajagopalan, Uma Maheswari; Nakamichi, Yu; Igarashi, Kei M; Kadono, Hirofumi; Tanifuji, Manabu

    2016-03-01

    In rodent olfactory bulb (OB), optical intrinsic signal imaging (OISI) is commonly used to investigate functional maps to odorant stimulations. However, in such studies, the spatial resolution in depth direction (z-axis) is lost because of the integration of light from different depths. To solve this problem, we propose functional optical coherence tomography (fOCT) with periodic stimulation and continuous recording. In fOCT experiments of in vivo rat OB, propionic acid and m-cresol were used as odor stimulus presentations. Such a periodic stimulation enabled us to detect the specific odor-responses from highly scattering brain tissue. Swept source OCT operating at a wavelength of 1334 nm and a frequency of 20 kHz, was employed with theoretical depth and lateral resolutions of 6.7 μm and 15.4 μm, respectively. We succeeded in visualizing 2D cross sectional fOCT map across the neural layer structure of OCT in vivo. The detected fOCT signals corresponded to a few glomeruli of the medial and lateral parts of dorsal OB. We also obtained 3D fOCT maps, which upon integration across z-axis agreed well with OISI results. We expect such an approach to open a window for investigating and possibly addressing toward inter/intra-layer connections at high resolutions in the future. PMID:27231593

  7. Subchronic inhalation exposure to 2-ethyl-1-hexanol impairs the mouse olfactory bulb via injury and subsequent repair of the nasal olfactory epithelium.

    PubMed

    Miyake, Mio; Ito, Yuki; Sawada, Masato; Sakai, Kiyoshi; Suzuki, Himiko; Sakamoto, Tatsuo; Sawamoto, Kazunobu; Kamijima, Michihiro

    2016-08-01

    The olfactory system can be a toxicological target of volatile organic compounds present in indoor air. Recently, 2-ethyl-1-hexanol (2E1H) emitted from adhesives and carpeting materials has been postulated to cause "sick building syndrome." Patients' symptoms are associated with an increased sense of smell. This investigation aimed to characterize the histopathological changes of the olfactory epithelium (OE) of the nasal cavity and the olfactory bulb (OB) in the brain, due to subchronic exposure to 2E1H. Male ICR mice were exposed to 0, 20, 60, or 150 ppm 2E1H for 8 h every day for 1 week, or 5 days per week for 1 or 3 months. After a 1-week exposure, the OE showed inflammation and degeneration, with a significant concentration-dependent reduction in the staining of olfactory receptor neurons and in the numbers of globose basal cells at ≥20 ppm. Regeneration occurred at 1 month along with an increase in the basal cells, but lymphocytic infiltration, expanded Bowman's glands, and a decrease in the olfactory receptor neurons were observed at 3 months. Intriguingly, the OB at 3 months showed a reduction in the diameters of the glomeruli and in the number of olfactory nerves and tyrosine hydroxylase-positive neurons, but an increased number of ionized calcium-binding adaptor molecule 1-positive microglia in glomeruli. Accordingly, 2E1H inhalation induced degeneration of the OE with the lowest-observed-adverse-effect level of 20 ppm. The altered number of functional cell components in the OB suggests that effects on olfactory sensation persist after subchronic exposure to 2E1H. PMID:27055686

  8. Organisation and tyrosine hydroxylase and calretinin immunoreactivity in the main olfactory bulb of paca (Cuniculus paca): a large caviomorph rodent.

    PubMed

    Sasahara, Tais Harumi de Castro; Leal, Leonardo Martins; Spillantini, Maria Grazia; Machado, Márcia Rita Fernandes

    2015-04-01

    The majority of neuroanatomical and chemical studies of the olfactory bulb have been performed in small rodents, such as rats and mice. Thus, this study aimed to describe the organisation and the chemical neuroanatomy of the main olfactory bulb (MOB) in paca, a large rodent belonging to the Hystricomorpha suborder and Caviomorpha infraorder. For this purpose, histological and immunohistochemical procedures were used to characterise the tyrosine hydroxylase (TH) and calretinin (CR) neuronal populations and their distribution. The paca MOB has eight layers: the olfactory nerve layer (ONL), the glomerular layer (GL), the external plexiform layer (EPL; subdivided into the inner and outer sublayers), the mitral cell layer (MCL), the internal plexiform layer (IPL), the granule cell layer (GCL), the periventricular layer and the ependymal layer. TH-ir neurons were found mostly in the GL, and moderate numbers of TH-ir neurons were scattered in the EPL. Numerous varicose fibres were distributed in the IPL and in the GCL. CR-ir neurons concentrated in the GL, around the base of the olfactory glomeruli. Most of the CR-ir neurons were located in the MCL, IPL and GCL. Some of the granule cells had an apical dendrite with a growth cone. The CR immunoreactivity was also observed in the ONL with olfactory nerves strongly immunostained. This study has shown that the MOB organisation in paca is consistent with the description in other mammals. The characterisation and distribution of the population of TH and CR in the MOB is not exclusively to this species. This large rodent shares common patterns to other caviomorph rodent, as guinea pig, and to the myomorph rodents, as mice, rats and hamsters.

  9. Calretinin-Periglomerular Interneurons in Mice Olfactory Bulb: Cells of Few Words

    PubMed Central

    Fogli Iseppe, Alex; Pignatelli, Angela; Belluzzi, Ottorino

    2016-01-01

    Within the olfactory bulb (OB), periglomerular (PG) cells consist of various types of interneurons, generally classified by their chemical properties such as neurotransmitter and calcium binding proteins. Calretinin (CR) characterizes morphologically and functionally the more numerous and one of the less known subpopulation of PG cells in the OB. Using of transgenic mice expressing eGFP under the CR promoter, we have tried to obtain the first functional characterization of these cells. Electrophysiological recordings were made in these cells using the patch-clamp technique in thin slices. Using ion substitution methods and specific blockers, we dissected the main voltage-dependent conductances present, obtaining a complete kinetic description for each of them. The more peculiar property of these cells from the electrophysiological point of view is the presence only of a single K-current, A-type – there is no trace of delayed rectifier or of Ca-dependent K-current. Other currents identified, isolated and fully characterized are a fast sodium current, a small L-type calcium current, and an inward rectifier, h-type cationic current. As a consequence of the peculiar complement of voltage-dependent conductances present in these cells, and in particular the absence of delayed-rectifier potassium currents, under the functional point of view these cells present two interesting properties. First, in response to prolonged depolarisations, after the inactivation of the A-current these cells behave as a purely ohmic elements, showing no outward rectification. Second, the CR cells studied can respond only with a single action potential to excitatory inputs; since they send inhibitory synapses to projection neurones, they seem to be designed to inhibit responses of the main neurones to isolated, random excitatory signals, rapidly losing their vetoing effect in response to more structured, repetitive excitatory signals. We propose that a possible role for these rather

  10. The olfactory bulb in newborn piglet is a reservoir of neural stem and progenitor cells.

    PubMed

    Martin, Lee J; Katzenelson, Alyssa; Koehler, Raymond C; Chang, Qing

    2013-01-01

    The olfactory bulb (OB) periventricular zone is an extension of the forebrain subventricular zone (SVZ) and thus is a source of neuroprogenitor cells and neural stem cells. While considerable information is available on the SVZ-OB neural stem cell (NSC)/neuroprogenitor cell (NPC) niche in rodents, less work has been done on this system in large animals. The newborn piglet is used as a preclinical translational model of neonatal hypoxic-ischemic brain damage, but information about the endogenous sources of NSCs/NPCs in piglet is needed to implement endogenous or autologous cell-based therapies in this model. We characterized NSC/NPC niches in piglet forebrain and OB-SVZ using western blotting, histological, and cell culture methods. Immunoblotting revealed nestin, a NSC/NPC marker, in forebrain-SVZ and OB-SVZ in newborn piglet. Several progenitor or newborn neuron markers, including Dlx2, musashi, doublecortin, and polysialated neural cell adhesion molecule were also detected in OB-SVZ by immunoblotting. Immunohistochemistry confirmed the presence of nestin, musashi, and doublecortin in forebrain-SVZ and OB-SVZ. Bromodeoxyuridine (BrdU) labeling showed that the forebrain-SVZ and OB-SVZ accumulate newly replicated cells. BrdU-positive cells were immunolabeled for astroglial, oligodendroglial, and neuronal markers. A lateral migratory pathway for newly born neuron migration to primary olfactory cortex was revealed by BrdU labeling and co-labeling for doublecortin and class III β tubulin. Isolated and cultured forebrain-SVZ and OB-SVZ cells from newborn piglet had the capacity to generate numerous neurospheres. Single cell clonal analysis of neurospheres revealed the capacity for self-renewal and multipotency. Neurosphere-derived cells differentiated into neurons, astrocytes, and oligodendrocytes and were amenable to permanent genetic tagging with lentivirus encoding green fluorescent protein. We conclude that the piglet OB-SVZ is a reservoir of NSCs and NPCs suitable

  11. Immunohistochemical localization of GABAergic key molecules in the main olfactory bulb of the Korean roe deer, Capreolus pygargus.

    PubMed

    Kim, Jeongtae; Takayama, Chitoshi; Park, Changnam; Ahn, Meejung; Moon, Changjong; Shin, Taekyun

    2015-09-01

    Gamma-amino butyric acid (GABA) negatively regulates the excitatory activity of neurons and is a predominant neurotransmitter in the nervous system. The olfactory bulb, the main center in the olfactory system, is modulated by inhibitory interneurons that use GABA as their main neurotransmitter. The present study aimed to evaluate GABAergic transmission in the main olfactory bulb (MOB) of the Korean roe deer (Capreolus pygargus) by examining the immunohistochemical localization of GABAergic key molecules, including glutamic acid decarboxylase (GAD), vesicular GABA transporter (VGAT), GABA transporters (GATs; GAT-1 and GAT-3), and potassium sodium chloride co-transporter 2 (KCC2). GAD, VGAT, and KCC2 were expressed in the glomerular layer (GL), external plexiform layer (ePL), mitral cell layer (ML), and granule cell layer (GrL). Intense GAT-1 expression was observed in the GL; GAT-1 expression was discernible in the ePL, ML, and GrL. However, intense GAT-3 expression was extensively observed in all layers of the MOB. These results suggest that substantial GABAergic synapses are present in the GL, ePL, ML, and GrL. Furthermore, the released GABA may be removed by GAT-1 and GAT-3 in the GL, and the majority of GABA, which is present in the ePL to GrL, may undergo reuptake by GAT-3. This is the first morphological and descriptive study of GABAergic transmission in the MOB of Korean roe deer. PMID:26115600

  12. Agrin-signalling is necessary for the integration of newly generated neurons in the adult olfactory bulb

    PubMed Central

    Burk, Katja; Desoeuvre, Angelique; Boutin, Camille; Smith, Martin A.; Kröger, Stephan; Bosio, Andreas; Tiveron, Marie-Catherine; Cremer, Harold

    2012-01-01

    In the adult forebrain new interneurons are continuously generated and integrated into the existing circuitry of the olfactory bulb. In an attempt to identify signals that regulate this synaptic integration process, we found strong expression of agrin in adult generated neuronal precursors that arrive in the olfactory bulb after their generation in the subventricular zone. While the agrin receptor components MuSK and Lrp4 were below detection level in neuron populations that represent synaptic targets for the new interneurons, the alternative receptor α3Na+K+ATPase was strongly expressed in mitral cells. Using a transplantation approach we demonstrate that agrin-deficient interneuron precursors migrate correctly into the OB. However, in contrast to wildtype neurons, which form synapses and survive for prolonged periods, mutant neurons do not mature and are rapidly eliminated. Using in vivo brain electroporation of the olfactory system we show that the transmembrane form of agrin alone is sufficient to mediate integration and demonstrate that excess transmembrane agrin increases the number of dendritic spines. Lastly, we provide in vivo evidence that an interaction between agrin and α3Na+K+ATPase is of functional importance in this system. PMID:22423096

  13. Olfactory bulb proteome dynamics during the progression of sporadic Alzheimer's disease: identification of common and distinct olfactory targets across Alzheimer-related co-pathologies

    PubMed Central

    Zelaya, María Victoria; Pérez-Valderrama, Estela; de Morentin, Xabier Martínez; Tuñon, Teresa; Ferrer, Isidro; Luquin, María Rosario; Fernandez-Irigoyen, Joaquín; Santamaría, Enrique

    2015-01-01

    Olfactory dysfunction is present in up to 90% of Alzheimer's disease (AD) patients. Although deposition of hyperphosphorylated tau and β-amyloid substrates are present in olfactory areas, the molecular mechanisms associated with decreased smell function are not completely understood. We have applied mass spectrometry-based quantitative proteomics to probe additional molecular disturbances in postmortem olfactory bulbs (OB) dissected from AD cases respect to neurologically intact controls (n=20, mean age 82.1 years). Relative proteome abundance measurements have revealed protein interaction networks progressively disturbed across AD stages suggesting an early imbalance in splicing factors, subsequent interrupted cycling of neurotransmitters, alteration in toxic and protective mechanisms of β-amyloid, and finally, a mitochondrial dysfunction together with disturbance in neuron-neuron adhesion. We also present novel molecular findings in the OB in an autopsy cohort composed by Lewy body disease (LBD), frontotemporal lobar degeneration (FTLD), mixed dementia, and progressive supranuclear palsy (PSP) cases (n = 41, mean age 79.7 years). Olfactory mediators deregulated during the progression of AD such as Visinin-like protein 1, RUFY3 protein, and Copine 6 were also differentially modulated in the OB in LBD, FTLD, and mixed dementia. Only Dipeptidyl aminopeptidase-like protein 6 showed a specific down-regulation in AD. However, no differences were observed in the olfactory expression of this protein panel in PSP subjects. This study demonstrates an olfactory progressive proteome modulation in AD, unveiling cross-disease similarities and differences especially for specific proteins involved in dendritic and axonic distributions that occur in the OB during the neurodegenerative process. PMID:26517091

  14. Extracting Behaviorally Relevant Traits from Natural Stimuli: Benefits of Combinatorial Representations at the Accessory Olfactory Bulb.

    PubMed

    Kahan, Anat; Ben-Shaul, Yoram

    2016-03-01

    For many animals, chemosensation is essential for guiding social behavior. However, because multiple factors can modulate levels of individual chemical cues, deriving information about other individuals via natural chemical stimuli involves considerable challenges. How social information is extracted despite these sources of variability is poorly understood. The vomeronasal system provides an excellent opportunity to study this topic due to its role in detecting socially relevant traits. Here, we focus on two such traits: a female mouse's strain and reproductive state. In particular, we measure stimulus-induced neuronal activity in the accessory olfactory bulb (AOB) in response to various dilutions of urine, vaginal secretions, and saliva, from estrus and non-estrus female mice from two different strains. We first show that all tested secretions provide information about a female's receptivity and genotype. Next, we investigate how these traits can be decoded from neuronal activity despite multiple sources of variability. We show that individual neurons are limited in their capacity to allow trait classification across multiple sources of variability. However, simple linear classifiers sampling neuronal activity from small neuronal ensembles can provide a substantial improvement over that attained with individual units. Furthermore, we show that some traits are more efficiently detected than others, and that particular secretions may be optimized for conveying information about specific traits. Across all tested stimulus sources, discrimination between strains is more accurate than discrimination of receptivity, and detection of receptivity is more accurate with vaginal secretions than with urine. Our findings highlight the challenges of chemosensory processing of natural stimuli, and suggest that downstream readout stages decode multiple behaviorally relevant traits by sampling information from distinct but overlapping populations of AOB neurons. PMID:26938460

  15. Extracting Behaviorally Relevant Traits from Natural Stimuli: Benefits of Combinatorial Representations at the Accessory Olfactory Bulb

    PubMed Central

    Kahan, Anat; Ben-Shaul, Yoram

    2016-01-01

    For many animals, chemosensation is essential for guiding social behavior. However, because multiple factors can modulate levels of individual chemical cues, deriving information about other individuals via natural chemical stimuli involves considerable challenges. How social information is extracted despite these sources of variability is poorly understood. The vomeronasal system provides an excellent opportunity to study this topic due to its role in detecting socially relevant traits. Here, we focus on two such traits: a female mouse’s strain and reproductive state. In particular, we measure stimulus-induced neuronal activity in the accessory olfactory bulb (AOB) in response to various dilutions of urine, vaginal secretions, and saliva, from estrus and non-estrus female mice from two different strains. We first show that all tested secretions provide information about a female’s receptivity and genotype. Next, we investigate how these traits can be decoded from neuronal activity despite multiple sources of variability. We show that individual neurons are limited in their capacity to allow trait classification across multiple sources of variability. However, simple linear classifiers sampling neuronal activity from small neuronal ensembles can provide a substantial improvement over that attained with individual units. Furthermore, we show that some traits are more efficiently detected than others, and that particular secretions may be optimized for conveying information about specific traits. Across all tested stimulus sources, discrimination between strains is more accurate than discrimination of receptivity, and detection of receptivity is more accurate with vaginal secretions than with urine. Our findings highlight the challenges of chemosensory processing of natural stimuli, and suggest that downstream readout stages decode multiple behaviorally relevant traits by sampling information from distinct but overlapping populations of AOB neurons. PMID:26938460

  16. Monitoring neurodegeneration in diabetes using adult neural stem cells derived from the olfactory bulb

    PubMed Central

    2013-01-01

    Introduction Neurons have the intrinsic capacity to produce insulin, similar to pancreatic cells. Adult neural stem cells (NSCs), which give rise to functional neurons, can be established and cultured not only by intracerebral collection, which requires difficult surgery, but also by collection from the olfactory bulb (OB), which is relatively easy. Adult neurogenesis in the hippocampus (HPC) is significantly decreased in diabetes patients. As a result, learning and memory functions, for which the HPC is responsible, decrease. Methods In the present study, we compared the effect of diabetes on neurogenesis and insulin expression in adult NSCs. Adult NSCs were derived from the HPC or OB of streptozotocin-induced diabetic rats. Comparative gene-expression analyses were carried out by using extracted tissues and established adult NSC cultures from the HPC or OB in diabetic rats. Results Diabetes progression influenced important genes that were required for insulin expression in both OB- and HPC-derived cells. Additionally, we found that the expression levels of several genes, such as voltage-gated sodium channels, glutamate transporters, and glutamate receptors, were significantly different in OB and HPC cells collected from diabetic rats. Conclusions By using identified diabetes-response genes, OB NSCs from diabetes patients can be used during diabetes progression to monitor processes that cause neurodegeneration in the central nervous system (CNS). Because hippocampal NSCs and OB NSCs exhibited similar gene-expression profiles during diabetes progression, OB NSCs, which are more easily collected and established than HPC NSCs, may potentially be used for screening of effective drugs for neurodegenerative disorders that cause malignant damage to CNS functions. PMID:23673084

  17. Partial Conservation between Mice and Humans in Olfactory Bulb Interneuron Transcription Factor Codes

    PubMed Central

    Fujiwara, Nana; Cave, John W.

    2016-01-01

    The mammalian main olfactory bulb (OB) has a large population of GABAergic inhibitory interneurons that contains several subtypes defined by the co-expression other neurotransmitters and calcium binding proteins. The three most commonly studied OB interneuron subtypes co-express either Calretinin, Calbindin, or Tyrosine hydroxylase (Th). Combinations of transcription factors used to specify the phenotype of progenitors are referred to as transcription factor codes, and the current understanding of transcription factor codes that specify OB inhibitory neuron phenotypes are largely based on studies in mice. The conservation of these transcription factor codes in the human OB, however, has not been investigated. The aim of this study was to establish whether transcription factor codes in OB interneurons are conserved between mice and humans. This study compared the co-expression of Foxp2, Meis2, Pax6, and Sp8 transcription factors with Calretinin, Calbindin, or Th in human and mouse OB interneurons. This analysis found strong conservation of Calretinin co-expression with Sp8 and Meis2 as well as Th co-expression with Pax6 and Meis2. This analysis also showed that selective Foxp2 co-expression with Calbindin was conserved between mice and humans, which suggests Foxp2 is a novel determinant of the OB Calbindin interneuron phenotype. Together, the findings in this study provide insight into the conservation of transcription codes for OB interneuron phenotypes between humans and mice, as well as reveal some important differences between the species. This advance in our understanding of transcription factor codes in OB interneurons provides an important complement to the codes that have been established for other regions within the mammalian central nervous system, such as the cortex and spinal cord. PMID:27489533

  18. Partial Conservation between Mice and Humans in Olfactory Bulb Interneuron Transcription Factor Codes.

    PubMed

    Fujiwara, Nana; Cave, John W

    2016-01-01

    The mammalian main olfactory bulb (OB) has a large population of GABAergic inhibitory interneurons that contains several subtypes defined by the co-expression other neurotransmitters and calcium binding proteins. The three most commonly studied OB interneuron subtypes co-express either Calretinin, Calbindin, or Tyrosine hydroxylase (Th). Combinations of transcription factors used to specify the phenotype of progenitors are referred to as transcription factor codes, and the current understanding of transcription factor codes that specify OB inhibitory neuron phenotypes are largely based on studies in mice. The conservation of these transcription factor codes in the human OB, however, has not been investigated. The aim of this study was to establish whether transcription factor codes in OB interneurons are conserved between mice and humans. This study compared the co-expression of Foxp2, Meis2, Pax6, and Sp8 transcription factors with Calretinin, Calbindin, or Th in human and mouse OB interneurons. This analysis found strong conservation of Calretinin co-expression with Sp8 and Meis2 as well as Th co-expression with Pax6 and Meis2. This analysis also showed that selective Foxp2 co-expression with Calbindin was conserved between mice and humans, which suggests Foxp2 is a novel determinant of the OB Calbindin interneuron phenotype. Together, the findings in this study provide insight into the conservation of transcription codes for OB interneuron phenotypes between humans and mice, as well as reveal some important differences between the species. This advance in our understanding of transcription factor codes in OB interneurons provides an important complement to the codes that have been established for other regions within the mammalian central nervous system, such as the cortex and spinal cord. PMID:27489533

  19. Afterhyperpolarization (AHP) regulates the frequency and timing of action potentials in the mitral cells of the olfactory bulb: role of olfactory experience

    PubMed Central

    Duménieu, Maël; Fourcaud-Trocmé, Nicolas; Garcia, Samuel; Kuczewski, Nicola

    2015-01-01

    Afterhyperpolarization (AHP) is a principal feedback mechanism in the control of the frequency and patterning of neuronal firing. In principal projection neurons of the olfactory bulb, the mitral cells (MCs), the AHP is produced by three separate components: classical potassium-mediated hyperpolarization, and the excitatory and inhibitory components, which are generated by the recurrent dendrodendritic synaptic transmission. Precise spike timing is involved in olfactory coding and learning, as well as in the appearance of population oscillatory activity. However, the contribution of the AHP and its components to these processes remains unknown. In this study, we demonstrate that the AHP is developed with the MC firing frequency and is dominated by the potassium component. We also show that recurrent synaptic transmission significantly modifies MC AHP and that the strength of the hyperpolarization produced by the AHP in the few milliseconds preceding the action potential (AP) emission determines MC firing frequency and AP timing. Moreover, we show that the AHP area is larger in younger animals, possibly owing to increased Ca2+ influx during MC firing. Finally, we show that olfactory experience selectively reduces the early component of the MC AHP (under 25 msec), thus producing a modification of the AP timing limited to the higher firing frequency. On the basis of these results, we propose that the AHP, and its susceptibility to be selectively modulated by the recurrent synaptic transmission and olfactory experience, participate in odor coding and learning by modifying the frequency and pattern of MC firing. PMID:26019289

  20. Acute changes in murine hippocampus and olfactory bulb after nasal instillation of varying size cerium dioxide particles.

    PubMed

    Liu, Yang; Li, Yuanyuan; Yang, Tongwang; Yang, Jing; Wang, He; Wu, Gang

    2016-01-01

    Cerium (Ce)-containing compounds are now widely applied in medicine, agriculture, and animal breeding. However, the effects of Ce on humans, especially on the central nervous system (CNS), remain to be determined. In order to investigate whether Ce exposure affected the CNS, the aim of this study was to expose female ICR mice to varying nanoparticle sizes of 35 nm and 300 nm, and to a mixture of 1-5 µM cerium dioxide (CeO2) particles through intranasal (i.n.) instillation at daily dose of 40 mg/kg body weight. Immunohistochemical data showed that glial fibrillary acidic protein expression (GFAP) increased significantly in the hippocampus and olfactory bulb in all Ce-administered groups. The ultrastructure of olfactory bulb cells displayed chromatin reduction. In the hippocampus decreased chromatin was associated with ribosome shedding as evidenced from transmission electron microscopy (TEM). No significant differences in immunohistochemistry were noted between varying sizes of CeO2 groups. The results of inductively coupled plasma-mass spectroscopy (ICP-MS) analysis group exposed to 1-5 µM demonstrated that Ce levels were significantly higher in whole brain (0.17 ng/mg) than for the control (0.04 ng/mg). Data thus demonstrated that i.n. instillation of different sized CeO2 particles induced damage in the olfactory bulb and hippocampus and that CeO2 particle size did not appear to play a role in the observed adverse responses. PMID:27599233

  1. Oligosynaptic pathways possibly relaying visceral and/or gustatory information to the olfactory bulb in the hedgehog tenrec.

    PubMed

    Künzle, H; Radtke-Schuller, S

    2001-04-27

    Using anterograde and retrograde transport of wheat germ agglutinin we showed that the parabrachial nucleus, known to receive second order visceral and gustatory afferents, might project directly to the anterior olfactory nucleus which is connected with the olfactory bulb (OfB). Only a small bulbar region is targeted directly by parabrachial fibers. This region is located immediately adjacent to the accessory OfB and may be closely related to, if not identical with the modified glomerular complex. To further substantiate the presence of true parabrachio-bulbar projections thyrosine hydroxylase immunohistochemistry was employed. The absence of immunoreactive neurons in the parabrachial nucleus and the different distribution patterns of immunoreactive fibers and axons labeled with wheat germ agglutinin conjugated to horseradish peroxidase in the target areas make it unlikely that catecholaminergic fibers were involved in the projections shown.

  2. The effect of bilirubin on the excitability of mitral cells in the olfactory bulb of the rat

    PubMed Central

    Chen, Xiao-Juan; Zhou, Hui-Qun; Ye, Hai-bo; Li, Chun-Yan; Zhang, Wei-Tian

    2016-01-01

    Olfactory dysfunction is a common clinical phenomenon observed in various liver diseases. Previous studies have shown a correlation between smell disorders and bilirubin levels in patients with hepatic diseases. Bilirubin is a well-known neurotoxin; however, its effect on neurons in the main olfactory bulb (MOB), the first relay in the olfactory system, has not been examined. We investigated the effect of bilirubin (>3 μM) on mitral cells (MCs), the principal output neurons of the MOB. Bilirubin increased the frequency of spontaneous firing and the frequency but not the amplitude of spontaneous excitatory postsynaptic currents (sEPSCs). TTX completely blocked sEPSCs in almost all of the cells tested. Bilirubin activity was partially blocked by N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepro pionic acid (AMPA) receptor antagonists. Furthermore, we found that bilirubin increased the frequency of intrinsic firing independent of synaptic transmission in MCs. Our findings suggest that bilirubin enhances glutamatergic transmission and strengthens intrinsic firing independent of synaptic transmission, all of which cause hyperexcitability in MCs. Our findings provide the basis for further investigation into the mechanisms underlying olfactory dysfunction that are often observed in patients with severe liver disease. PMID:27611599

  3. The effect of bilirubin on the excitability of mitral cells in the olfactory bulb of the rat.

    PubMed

    Chen, Xiao-Juan; Zhou, Hui-Qun; Ye, Hai-Bo; Li, Chun-Yan; Zhang, Wei-Tian

    2016-01-01

    Olfactory dysfunction is a common clinical phenomenon observed in various liver diseases. Previous studies have shown a correlation between smell disorders and bilirubin levels in patients with hepatic diseases. Bilirubin is a well-known neurotoxin; however, its effect on neurons in the main olfactory bulb (MOB), the first relay in the olfactory system, has not been examined. We investigated the effect of bilirubin (>3 μM) on mitral cells (MCs), the principal output neurons of the MOB. Bilirubin increased the frequency of spontaneous firing and the frequency but not the amplitude of spontaneous excitatory postsynaptic currents (sEPSCs). TTX completely blocked sEPSCs in almost all of the cells tested. Bilirubin activity was partially blocked by N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepro pionic acid (AMPA) receptor antagonists. Furthermore, we found that bilirubin increased the frequency of intrinsic firing independent of synaptic transmission in MCs. Our findings suggest that bilirubin enhances glutamatergic transmission and strengthens intrinsic firing independent of synaptic transmission, all of which cause hyperexcitability in MCs. Our findings provide the basis for further investigation into the mechanisms underlying olfactory dysfunction that are often observed in patients with severe liver disease. PMID:27611599

  4. Gestational methyl donor deficiency alters key proteins involved in neurosteroidogenesis in the olfactory bulbs of newborn female rats and is associated with impaired olfactory performance.

    PubMed

    El Hajj Chehadeh, Sarah; Pourié, Grégory; Martin, Nicolas; Alberto, Jean-Marc; Daval, Jean-Luc; Guéant, Jean-Louis; Leininger-Muller, Brigitte

    2014-03-28

    Gestational methyl donor deficiency (MDD) leads to growth retardation as well as to cognitive and motor disorders in 21-d-old rat pups. These disorders are related to impaired neurogenesis in the cerebral neurogenic areas. Olfactory bulbs (OB), the main target of neuronal progenitors originating from the subventricular zone, play a critical role during the postnatal period by allowing the pups to identify maternal odour. We hypothesised that growth retardation could result from impaired suckling due to impaired olfactory discrimination through imbalanced apoptosis/neurogenesis in the OB. Since neurosteroidogenesis modulates neurogenesis in OB, in the present study, we investigated whether altered neurosteroidogenesis could explain some these effects. Pups born to dams fed a normal diet (n 24) and a MDD diet (n 27) were subjected to olfactory tests during the lactation and weaning periods (n 24 and 20, respectively). We studied the markers of apoptosis/neurogenesis and the expression levels of the key neurosteroidogenic enzyme aromatase, the cholesterol-transfer protein StAR (steroidogenic acute regulatory protein) and the ERα oestrogen receptor and the content of oestradiol in OB. The 21-d-old MDD female pups displayed lower body weight and impaired olfactory discrimination when compared with the control pups. MDD led to greater homocysteine accumulation and more pronounced apoptosis, along with impaired cell proliferation in the OB of female pups. The expression levels of aromatase, StAR and ERα as well as the content of oestradiol were lower in the OB of the MDD female pups than in those of the control female pups. In conclusion, gestational MDD may alter olfactory discrimination performances by affecting neurogenesis, apoptosis and neurosteroidogenesis in OB in a sex-dependent manner. It may be involved in growth retardation through impaired suckling.

  5. An additional discovery of salamanders, Salamandrella keyserlingii Dybowski, with no blood vessels in the brain parenchyma except in the olfactory bulb.

    PubMed

    Takahashi, K; Ninomiya, T

    1992-03-01

    The brain parenchyma of Salamandrella keyserlingii Dybowski (SKD) is not vascularized except in the olfactory bulb. In the brains of SKD, neuronal and glial perikarya are seen densely aggregated at the periventricular regions and no blood vessels enter the brain parenchyma from the meningeal vessels. Former investigators have discovered no blood vessels in the brains of nine species of salamanders in the Hynobiidae, all of which inhabit Japan. This report adds one more avascular species of salamander which is found in Hokkaido, Japan. The reasons why the brain of Hynobiid salamanders is not vascularized and why only the olfactory bulbs are vascularized cannot be speculated on at the present time.

  6. Potassium Currents of Olfactory Bulb Juxtaglomerular Cells: Characterization, Simulation, and Implications for Plateau Potential Firing

    PubMed Central

    Masurkar, Arjun V.; Chen, Wei R.

    2011-01-01

    Odor identity is encoded by the activity of olfactory bulb glomeruli, which receive primary sensory input and transfer it to projection neurons. Juxtaglomerular cells (JGCs) may influence glomerular processing via firing of long lasting plateau potentials. Though inward currents have been investigated, little is known regarding potassium current contribution to JGC plateau potentials. We pursued study of these currents, with the overarching goal of creating components for a computational model of JGC plateau potential firing. In conditions minimizing calcium-activated potassium current (IK(Ca)), we used whole cell voltage clamp and in vitro slice preparations to characterize three potassium currents in rat JGCs. The prominent component Ikt1 displayed rapid kinetics (τ10%−90% rise 0.6–2ms, τinactivation 5–10ms) and was blocked by high concentration 4-AP (5mM) and TEA (40mM). It had half maximal activation at −10mV (V½max) and little inactivation at rest. Ikt2, with slower kinetics (τ10%−90% rise 11–15ms, τinactivation 100–300ms), was blocked by low concentration 4-AP (0.5mM) and TEA (5mM). The V½max was 0mV and inactivation was also minimal at rest. Sustained current Ikt3 showed sensitivity to low concentration 4-AP and TEA, and had V½max of +10mV. Further experiments, in conditions of physiologic calcium buffering, suggested that IK(Ca) contributed to Ikt3 with minimal effect on plateau potential evolution. We transformed these characterizations into Hodgkin-Huxley models that robustly mimicked experimental data. Further simulation demonstrated that Ikt1 would be most efficiently activated by plateau potential waveforms, predicting a critical role in shaping JGC firing. These studies demonstrated that JGCs possess a unique potassium current profile, with delayed rectifier (Ikt3), atypical A-current (Ikt1), and D-current (Ikt2) in accordance with known expression patterns in OB glomeruli. Our simulations also provide an initial framework for

  7. Human olfactory bulb neural stem cells expressing hNGF restore cognitive deficit in Alzheimer's disease rat model.

    PubMed

    Marei, Hany E S; Farag, Amany; Althani, Asma; Afifi, Nahla; Abd-Elmaksoud, Ahmed; Lashen, Samah; Rezk, Shaymaa; Pallini, Roberto; Casalbore, Patrizia; Cenciarelli, Carlo

    2015-01-01

    In this study, we aim to demonstrate the fate of allogenic adult human olfactory bulb neural stem/progenitor cells (OBNSC/NPCs) transplanted into the rat hippocampus treated with ibotenic acid (IBO), a neurotoxicant specific to hippocampal cholinergic neurons that are lost in Alzheimer's disease. We assessed their possible ability to survive, integrate, proliferate, and differentiate into different neuronal and glial elements: we also evaluate their possible therapeutic potential, and the mechanism(s) relevant to neuroprotection following their engraftment into the CNS milieu. OBNSC/NPCs were isolated from adult human olfactory bulb patients, genetically engineered to express GFP and human nerve growth factor (hNGF) by lentivirus-mediated infection, and stereotaxically transplanted into the hippocampus of IBO-treated animals and controls. Stereological analysis of engrafted OBNSCs eight weeks post transplantation revealed a 1.89 fold increase with respect to the initial cell population, indicating a marked ability for survival and proliferation. In addition, 54.71 ± 11.38%, 30.18 ± 6.00%, and 15.09 ± 5.38% of engrafted OBNSCs were identified by morphological criteria suggestive of mature neurons, oligodendrocytes and astrocytes respectively. Taken together, this work demonstrated that human OBNSCs expressing NGF ameliorate the cognitive deficiencies associated with IBO-induced lesions in AD model rats, and the improvement can probably be attributed primarily to neuronal and glial cell replacement as well as the trophic influence exerted by the secreted NGF.

  8. Electrophysiological Evidence for a Direct Link between the Main and Accessory Olfactory Bulbs in the Adult Rat

    PubMed Central

    Vargas-Barroso, Victor; Ordaz-Sánchez, Benito; Peña-Ortega, Fernando; Larriva-Sahd, Jorge A.

    2016-01-01

    It is accepted that the main- and accessory- olfactory systems exhibit overlapping responses to pheromones and odorants. We performed whole-cell patch-clamp recordings in adult rat olfactory bulb slices to define a possible interaction between the first central relay of these systems: the accessory olfactory bulb (AOB) and the main olfactory bulb (MOB). This was tested by applying electrical field stimulation in the dorsal part of the MOB while recording large principal cells (LPCs) of the anterior AOB (aAOB). Additional recordings of LPCs were performed at either side of the plane of intersection between the aAOB and posterior-AOB (pAOB) halves, or linea alba, while applying field stimulation to the opposite half. A total of 92 recorded neurons were filled during whole-cell recordings with biocytin and studied at the light microscope. Neurons located in the aAOB (n = 6, 8%) send axon collaterals to the MOB since they were antidromically activated in the presence of glutamate receptor antagonists (APV and CNQX). Recorded LPCs evoked orthodromic excitatory post-synaptic responses (n = 6, aAOB; n = 1, pAOB) or antidromic action potentials (n = 8, aAOB; n = 7, pAOB) when applying field stimulation to the opposite half of the recording site (e.g., recording in aAOB; stimulating in pAOB, and vice-versa). Observation of the filled neurons revealed that indeed, LPCs send axon branches that cross the linea alba to resolve in the internal cellular layer. Additionally, LPCs of the aAOB send axon collaterals to dorsal-MOB territory. Notably, while performing AOB recordings we found a sub-population of neurons (24% of the total) that exhibited voltage-dependent bursts of action potentials. Our findings support the existence of: 1. a direct projection from aAOB LPCs to dorsal-MOB, 2. physiologically active synapses linking aAOB and pAOB, and 3. pacemaker-like neurons in both AOB halves. This work was presented in the form of an Abstract on SfN 2014 (719.14/EE17). PMID:26858596

  9. Electrophysiological Evidence for a Direct Link between the Main and Accessory Olfactory Bulbs in the Adult Rat.

    PubMed

    Vargas-Barroso, Victor; Ordaz-Sánchez, Benito; Peña-Ortega, Fernando; Larriva-Sahd, Jorge A

    2015-01-01

    It is accepted that the main- and accessory- olfactory systems exhibit overlapping responses to pheromones and odorants. We performed whole-cell patch-clamp recordings in adult rat olfactory bulb slices to define a possible interaction between the first central relay of these systems: the accessory olfactory bulb (AOB) and the main olfactory bulb (MOB). This was tested by applying electrical field stimulation in the dorsal part of the MOB while recording large principal cells (LPCs) of the anterior AOB (aAOB). Additional recordings of LPCs were performed at either side of the plane of intersection between the aAOB and posterior-AOB (pAOB) halves, or linea alba, while applying field stimulation to the opposite half. A total of 92 recorded neurons were filled during whole-cell recordings with biocytin and studied at the light microscope. Neurons located in the aAOB (n = 6, 8%) send axon collaterals to the MOB since they were antidromically activated in the presence of glutamate receptor antagonists (APV and CNQX). Recorded LPCs evoked orthodromic excitatory post-synaptic responses (n = 6, aAOB; n = 1, pAOB) or antidromic action potentials (n = 8, aAOB; n = 7, pAOB) when applying field stimulation to the opposite half of the recording site (e.g., recording in aAOB; stimulating in pAOB, and vice-versa). Observation of the filled neurons revealed that indeed, LPCs send axon branches that cross the linea alba to resolve in the internal cellular layer. Additionally, LPCs of the aAOB send axon collaterals to dorsal-MOB territory. Notably, while performing AOB recordings we found a sub-population of neurons (24% of the total) that exhibited voltage-dependent bursts of action potentials. Our findings support the existence of: 1. a direct projection from aAOB LPCs to dorsal-MOB, 2. physiologically active synapses linking aAOB and pAOB, and 3. pacemaker-like neurons in both AOB halves. This work was presented in the form of an Abstract on SfN 2014 (719.14/EE17).

  10. Electrophysiological Evidence for a Direct Link between the Main and Accessory Olfactory Bulbs in the Adult Rat.

    PubMed

    Vargas-Barroso, Victor; Ordaz-Sánchez, Benito; Peña-Ortega, Fernando; Larriva-Sahd, Jorge A

    2015-01-01

    It is accepted that the main- and accessory- olfactory systems exhibit overlapping responses to pheromones and odorants. We performed whole-cell patch-clamp recordings in adult rat olfactory bulb slices to define a possible interaction between the first central relay of these systems: the accessory olfactory bulb (AOB) and the main olfactory bulb (MOB). This was tested by applying electrical field stimulation in the dorsal part of the MOB while recording large principal cells (LPCs) of the anterior AOB (aAOB). Additional recordings of LPCs were performed at either side of the plane of intersection between the aAOB and posterior-AOB (pAOB) halves, or linea alba, while applying field stimulation to the opposite half. A total of 92 recorded neurons were filled during whole-cell recordings with biocytin and studied at the light microscope. Neurons located in the aAOB (n = 6, 8%) send axon collaterals to the MOB since they were antidromically activated in the presence of glutamate receptor antagonists (APV and CNQX). Recorded LPCs evoked orthodromic excitatory post-synaptic responses (n = 6, aAOB; n = 1, pAOB) or antidromic action potentials (n = 8, aAOB; n = 7, pAOB) when applying field stimulation to the opposite half of the recording site (e.g., recording in aAOB; stimulating in pAOB, and vice-versa). Observation of the filled neurons revealed that indeed, LPCs send axon branches that cross the linea alba to resolve in the internal cellular layer. Additionally, LPCs of the aAOB send axon collaterals to dorsal-MOB territory. Notably, while performing AOB recordings we found a sub-population of neurons (24% of the total) that exhibited voltage-dependent bursts of action potentials. Our findings support the existence of: 1. a direct projection from aAOB LPCs to dorsal-MOB, 2. physiologically active synapses linking aAOB and pAOB, and 3. pacemaker-like neurons in both AOB halves. This work was presented in the form of an Abstract on SfN 2014 (719.14/EE17). PMID:26858596

  11. Linear correlation between the number of olfactory sensory neurons expressing a given mouse odorant receptor gene and the total volume of the corresponding glomeruli in the olfactory bulb

    PubMed Central

    Bressel, Olaf Christian; Khan, Mona

    2015-01-01

    ABSTRACT Chemosensory specificity in the main olfactory system of the mouse relies on the expression of ∼1,100 odorant receptor (OR) genes across millions of olfactory sensory neurons (OSNs) in the main olfactory epithelium (MOE), and on the coalescence of OSN axons into ∼3,600 glomeruli in the olfactory bulb. A traditional approach for visualizing OSNs and their axons consists of tagging an OR gene genetically with an axonal marker that is cotranslated with the OR by virtue of an internal ribosome entry site (IRES). Here we report full cell counts for 15 gene‐targeted strains of the OR‐IRES‐marker design coexpressing a fluorescent protein. These strains represent 11 targeted OR genes, a 1% sample of the OR gene repertoire. We took an empirical, “count every cell” strategy: we counted all fluorescent cell profiles with a nuclear profile within the cytoplasm, on all serial coronal sections under a confocal microscope, a total of 685,673 cells in 56 mice at postnatal day 21. We then applied a strain‐specific Abercrombie correction to these OSN counts in order to obtain a closer approximation of the true OSN numbers. We found a 17‐fold range in the average (corrected) OSN number across these 11 OR genes. In the same series of coronal sections, we then determined the total volume of the glomeruli (TGV) formed by coalescence of the fluorescent axons. We found a strong linear correlation between OSN number and TGV, suggesting that TGV can be used as a surrogate measurement for estimating OSN numbers in these gene‐targeted strains. J. Comp. Neurol. 524:199–209, 2016. © 2015 Wiley Periodicals, Inc. PMID:26100963

  12. Neuroanatomical relationships between FMRFamide-immunoreactive components of the nervus terminalis and the topology of olfactory bulbs in teleost fish.

    PubMed

    D'Aniello, Biagio; Polese, Gianluca; Luongo, Luciano; Scandurra, Anna; Magliozzi, Laura; Aria, Massimo; Pinelli, Claudia

    2016-04-01

    The nervus terminalis (NT) is the most anterior of the vertebrate cranial nerves. In teleost fish, the NT runs across all olfactory components and shows high morphological variability within this taxon. We compare the anatomical distribution, average number and size of the FMRFamide-immunoreactive (ir) NT cells of fourteen teleost species with different positions of olfactory bulbs (OBs) with respect to the ventral telencephalic area. Based on the topology of the OBs, three different neuroanatomical organizations of the telencephalon can be defined, viz., fish having sessile (Type I), pseudosessile (short stalked; Type II) or stalked (Type III) OBs. Type III topology of OBs appears to be a feature associated with more basal species, whereas Types I and II occur in derived and in basal species. The displacement of the OBs is positively correlated with the peripheral distribution of the FMRFamide-ir NT cells. The number of cells is negatively correlated with the size of the cells. A dependence analysis related to the type of OB topology revealed a positive relationship with the number of cells and with the size of the cells, with Type I and II topologies of OBs showing significantly fewer cells and larger cells than Type III. A dendrogram based on similarities obtained by taking into account all variables under study, i.e., the number and size of the FMRFamide-ir NT cells and the topology of OBs, does not agree with the phylogenetic relationships amongst species, suggesting that divergent or convergent evolutionary phenomena produced the olfactory components studied.

  13. Direct visualization of cell movement in the embryonic olfactory bulb using green fluorescent protein transgenic mice: evidence for rapid tangential migration of neural cell precursors.

    PubMed

    Yamamoto, Kazuhiro; Yamaguchi, Masahiro; Okabe, Shigeo

    2005-02-01

    We analyzed motile behavior of neuronal precursor cells in the intact olfactory bulbs (OBs) using transgenic mice expressing GFP under the control of T alpha 1 tubulin promoter. In the olfactory bulbs at the embryonic days 12.5-14.5, a large number of immature neurons expressed GFP in this transgenic line. Embryonic OBs were maintained in an organ culture system and the migratory behavior of GFP-positive cells was analyzed by time-lapse confocal microscopy. We observed rapid tangential movement of GFP-positive cells in the ventral olfactory bulb. In contrast to the typical bipolar morphology of translocating immature neurons within the developing cortex, the motile cells had neither leading nor trailing processes and changed their overall shape frequently. Comparison of the behavior of cells expressing GFP under the control of T alpha 1 tubulin or nestin promoter revealed that rapid motility was specific to cells in the neuronal lineage. The rapid movement was sensitive to an actin perturbing reagent and also dependent on the calcium influx through L-type calcium channels. These results indicate the presence of a specific form of precursor cell migration in the embryonic olfactory bulb.

  14. Gene expression changes in the olfactory bulb of mice induced by exposure to diesel exhaust are dependent on animal rearing environment.

    PubMed

    Yokota, Satoshi; Hori, Hiroshi; Umezawa, Masakazu; Kubota, Natsuko; Niki, Rikio; Yanagita, Shinya; Takeda, Ken

    2013-01-01

    There is an emerging concern that particulate air pollution increases the risk of cranial nerve disease onset. Small nanoparticles, mainly derived from diesel exhaust particles reach the olfactory bulb by their nasal depositions. It has been reported that diesel exhaust inhalation causes inflammation of the olfactory bulb and other brain regions. However, these toxicological studies have not evaluated animal rearing environment. We hypothesized that rearing environment can change mice phenotypes and thus might alter toxicological study results. In this study, we exposed mice to diesel exhaust inhalation at 90 µg/m(3), 8 hours/day, for 28 consecutive days after rearing in a standard cage or environmental enrichment conditions. Microarray analysis found that expression levels of 112 genes were changed by diesel exhaust inhalation. Functional analysis using Gene Ontology revealed that the dysregulated genes were involved in inflammation and immune response. This result was supported by pathway analysis. Quantitative RT-PCR analysis confirmed 10 genes. Interestingly, background gene expression of the olfactory bulb of mice reared in a standard cage environment was changed by diesel exhaust inhalation, whereas there was no significant effect of diesel exhaust exposure on gene expression levels of mice reared with environmental enrichment. The results indicate for the first time that the effect of diesel exhaust exposure on gene expression of the olfactory bulb was influenced by rearing environment. Rearing environment, such as environmental enrichment, may be an important contributive factor to causation in evaluating still undefined toxic environmental substances such as diesel exhaust.

  15. Olfactory Bulb [alpha][subscript 2]-Adrenoceptor Activation Promotes Rat Pup Odor-Preference Learning via a cAMP-Independent Mechanism

    ERIC Educational Resources Information Center

    Shakhawat, Amin MD.; Harley, Carolyn W.; Yuan, Qi

    2012-01-01

    In this study, three lines of evidence suggest a role for [alpha][subscript 2]-adrenoreceptors in rat pup odor-preference learning: olfactory bulb infusions of the [alpha][subscript 2]-antagonist, yohimbine, prevents learning; the [alpha][subscript 2]-agonist, clonidine, paired with odor, induces learning; and subthreshold clonidine paired with…

  16. Functional imaging of olfaction by CBV fMRI in monkeys: insight into the role of olfactory bulb in habituation.

    PubMed

    Zhao, Fuqiang; Holahan, Marie A; Houghton, Andrea K; Hargreaves, Richard; Evelhoch, Jeffrey L; Winkelmann, Christopher T; Williams, Donald S

    2015-02-01

    Cerebral blood volume (CBV) fMRI with superparamagnetic iron oxide nanoparticles (USPIO) as contrast agent was used to investigate the odorant-induced olfaction in anesthetized rhesus monkeys. fMRI data were acquired in 24 axial slices covering the entire brain, with isoamyl-acetate as the odor stimulant. For each experiment, multiple fMRI measurements were made during a 1- or 2-h period, with each measurement consisting of a baseline period, a stimulation period, and a recovery period. Three different stimulation paradigms with a stimulation period of 1 min, 2 min, or 8 min, respectively, were used to study the olfactory responses in the olfactory bulb (OB). Odorant-induced CBV increases were observed in the OB of each individual monkey. The spatial and temporal activation patterns were reproducible within and between animals. The sensitivity of CBV fMRI in OB was comparable with the sensitivities reported in previous animal fMRI studies. The CBV responses during the 1-min, 2-min, or 8-min odor stimulation period were relatively stable, and did not show attenuation. The amplitudes of CBV response to the repeated stimuli during the 1- or 2-h period were also stable. The stable CBV response in the OB to both continuous and repeated odor stimuli suggests that the OB may not play a major role in olfactory habituation. The technical approach described in this report can enable more extensive fMRI studies of olfactory processing in OB of both humans and non-human primates. PMID:25498426

  17. Postnatal administration of dihydrotestosterone to the male rat abolishes sexual dimorphism in the accessory olfactory bulb: a volumetric study.

    PubMed

    Valencia, A; Collado, P; Calés, J M; Segovia, S; Pérez Laso, C; Rodríguez Zafra, M; Guillamón, A

    1992-07-24

    The regulatory action of the non-aromatizable androgen dihydrotestosterone (DHT) on sexual differentiation of the volume of the rat accessory olfactory bulb (AOB) was studied. Postnatal treatment with DHT (180 micrograms/day) carried out daily between days 6 and 20 produced a drastic reduction in overall AOB size and that of its constituent neural layers in genetic males with respect to intact and control males. The volumetric measures found in DHT-treated males did not differ from those shown by the intact females. These results, which indicate a demasculinization and a feminization of the AOB volume in gonadally intact male rats induced by DHT, are discussed in relation to the presumably regulatory role of DHT on neuron populations during the sexual organizational process of the brain.

  18. Population imaging at subcellular resolution supports specific and local inhibition by granule cells in the olfactory bulb

    PubMed Central

    Wienisch, Martin; Murthy, Venkatesh N.

    2016-01-01

    Information processing in early sensory regions is modulated by a diverse range of inhibitory interneurons. We sought to elucidate the role of olfactory bulb interneurons called granule cells (GCs) in odor processing by imaging the activity of hundreds of these cells simultaneously in mice. Odor responses in GCs were temporally diverse and spatially disperse, with some degree of non-random, modular organization. The overall sparseness of activation of GCs was highly correlated with the extent of glomerular activation by odor stimuli. Increasing concentrations of single odorants led to proportionately larger population activity, but some individual GCs had non-monotonic relations to concentration due to local inhibitory interactions. Individual dendritic segments could sometimes respond independently to odors, revealing their capacity for compartmentalized signaling in vivo. Collectively, the response properties of GCs point to their role in specific and local processing, rather than global operations such as response normalization proposed for other interneurons. PMID:27388949

  19. Glycyrrhizin ameliorates oxidative stress and inflammation in hippocampus and olfactory bulb in lithium/pilocarpine-induced status epilepticus in rats.

    PubMed

    González-Reyes, Susana; Santillán-Cigales, Juan Jair; Jiménez-Osorio, Angélica Saraí; Pedraza-Chaverri, José; Guevara-Guzmán, Rosalinda

    2016-10-01

    Glycyrrhizin (GL) is a triterpene present in the roots and rhizomes of Glycyrrhiza glabra that has anti-inflammatory, hepatoprotective and neuroprotective effects. Recently, it was demonstrated that GL produced neuroprotective effects on the postischemic brain as well as on the kainic acid injury model in rats. In addition to this, GL also prevented excitotoxic effects on primary cultures. The aims of the present study were to evaluate GL scavenging properties and to investigate GL's effect on oxidative stress and inflammation in the lithium/pilocarpine-induced seizure model in two cerebral regions, hippocampus and olfactory bulb, at acute time intervals (3 or 24h) after status epilepticus (SE). Fluorometric methods showed that GL scavenged three reactive oxygen species: hydrogen peroxide, peroxyl radicals and superoxide anions. In contrast, GL was unable to scavenge peroxynitrite, hydroxyl radicals, singlet oxygen and 2,2-diphenil-1-picrylhydrazyl (DPPH) radicals suggesting that GL is a weak scavenger. Additionally, administration of GL (50mg/kg, i.p.) 30min before pilocarpine administration significantly suppressed oxidative stress. Moreover, malondialdehyde levels were diminished and glutathione levels were maintained at control values in both cerebral regions at 3 and 24 after SE. At 24h after SE, glutathione S-transferase and superoxide dismutase activity increased in the hippocampus, while both glutathione reductase and glutathione peroxidase activity were unchanged in the olfactory bulb at that time. In addition, GL suppressed the induction of the proinflammatory cytokines interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) in both cerebral regions evaluated. These results suggest that GL confers protection against pilocarpine damage via antioxidant and anti-inflammatory effects. PMID:27490898

  20. Glycyrrhizin ameliorates oxidative stress and inflammation in hippocampus and olfactory bulb in lithium/pilocarpine-induced status epilepticus in rats.

    PubMed

    González-Reyes, Susana; Santillán-Cigales, Juan Jair; Jiménez-Osorio, Angélica Saraí; Pedraza-Chaverri, José; Guevara-Guzmán, Rosalinda

    2016-10-01

    Glycyrrhizin (GL) is a triterpene present in the roots and rhizomes of Glycyrrhiza glabra that has anti-inflammatory, hepatoprotective and neuroprotective effects. Recently, it was demonstrated that GL produced neuroprotective effects on the postischemic brain as well as on the kainic acid injury model in rats. In addition to this, GL also prevented excitotoxic effects on primary cultures. The aims of the present study were to evaluate GL scavenging properties and to investigate GL's effect on oxidative stress and inflammation in the lithium/pilocarpine-induced seizure model in two cerebral regions, hippocampus and olfactory bulb, at acute time intervals (3 or 24h) after status epilepticus (SE). Fluorometric methods showed that GL scavenged three reactive oxygen species: hydrogen peroxide, peroxyl radicals and superoxide anions. In contrast, GL was unable to scavenge peroxynitrite, hydroxyl radicals, singlet oxygen and 2,2-diphenil-1-picrylhydrazyl (DPPH) radicals suggesting that GL is a weak scavenger. Additionally, administration of GL (50mg/kg, i.p.) 30min before pilocarpine administration significantly suppressed oxidative stress. Moreover, malondialdehyde levels were diminished and glutathione levels were maintained at control values in both cerebral regions at 3 and 24 after SE. At 24h after SE, glutathione S-transferase and superoxide dismutase activity increased in the hippocampus, while both glutathione reductase and glutathione peroxidase activity were unchanged in the olfactory bulb at that time. In addition, GL suppressed the induction of the proinflammatory cytokines interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) in both cerebral regions evaluated. These results suggest that GL confers protection against pilocarpine damage via antioxidant and anti-inflammatory effects.

  1. Freezing to the predator odor 2,4,5 dihydro 2,5 trimethylthiazoline (TMT) is disrupted by olfactory bulb removal but not trigeminal deafferentation.

    PubMed

    Ayers, Luke W; Asok, Arun; Heyward, Frankie D; Rosen, Jeffrey B

    2013-09-15

    2,4,5 dihydro 2,5 trimethylthiazoline (TMT) is a synthesized component of red fox anal secretions that reliably elicits defensive behaviors in rats and mice. TMT differs from other predator odors because it is a single molecule, it can be synthesized in large quantities, and the dose for exposure is highly controllable in an experimental setting. TMT has become a popular tool for studying the brain mechanisms that mediate innate fear behavior to olfactory stimuli. However, this view of TMT as a biologically relevant olfactory stimulus has been challenged by suggestions that the odor elicits fear behavior due to its irritating properties, presumably working through a nociceptive mechanism. To address this criticism our lab measured freezing behavior in rats during exposures to 2 odors (TMT and butyric acid) and H2O (no odor control) following either surgical transection of the trigeminal nerves or ablation of the olfactory bulbs. Our findings (Experiment 1) indicate that freezing behavior to TMT requires an intact olfactory system, as indicated by the loss of freezing following olfactory bulb removal. Experiment 2 revealed that rats with trigeminal nerve transection freeze normally to TMT, suggesting the olfactory system mediates this behavior to TMT. A replication of Experiment 1 that included contextual fear conditioning revealed that the decreased freezing behavior was not due to an inability of olfactory bulb ablated rats to freeze (Experiment 3). Taken together, these findings support TMT's role as an ecologically relevant predator odor useful in experiments of unconditioned fear that is mediated via olfaction and not nociception. PMID:23831303

  2. Altered Morphologies and Functions of the Olfactory Bulb and Hippocampus Induced by miR-30c

    PubMed Central

    Sun, Tingting; Li, Tianpeng; Davies, Henry; Li, Weiyun; Yang, Jing; Li, Shanshan; Ling, Shucai

    2016-01-01

    Adult neurogenesis is considered to contribute to a certain degree of plasticity for the brain. However, the effects of adult-born neurons on the brain are still largely unknown. Here, we specifically altered the expression of miR-30c in the subventricular zone (SVZ) and dentate gyrus (DG) by stereotaxic injection with their respective up- and down-regulated lentiviruses. Results showed an increased level of miR-30c enhanced adult neurogenesis by prompting cell-cycles of stem cells, whereas down-regulated miR-30c led to the opposite results. When these effects of miR-30c lasted for 3 months, we detected significant morphological changes in the olfactory bulb (OB) and lineage alteration in the hippocampus. Tests of olfactory sensitivity and associative and spatial memory showed that a certain amount of adult-born neurons are essential for the normal functions of the OB and hippocampus, but there also exist redundant newborn neurons that do not further improve the functioning of these areas. Our study revealed the interactions between miRNA, adult neurogenesis, brain morphology and function, and this provides a novel insight into understanding the role of newborn neurons in the adult brain. PMID:27242411

  3. Anosmin-1 over-expression increases adult neurogenesis in the subventricular zone and neuroblast migration to the olfactory bulb.

    PubMed

    García-González, Diego; Murcia-Belmonte, Verónica; Esteban, Pedro F; Ortega, Felipe; Díaz, David; Sánchez-Vera, Irene; Lebrón-Galán, Rafael; Escobar-Castañondo, Laura; Martínez-Millán, Luis; Weruaga, Eduardo; García-Verdugo, José Manuel; Berninger, Benedikt; de Castro, Fernando

    2016-01-01

    New subventricular zone (SVZ)-derived neuroblasts that migrate via the rostral migratory stream are continuously added to the olfactory bulb (OB) of the adult rodent brain. Anosmin-1 (A1) is an extracellular matrix protein that binds to FGF receptor 1 (FGFR1) to exert its biological effects. When mutated as in Kallmann syndrome patients, A1 is associated with severe OB morphogenesis defects leading to anosmia and hypogonadotropic hypogonadism. Here, we show that A1 over-expression in adult mice strongly increases proliferation in the SVZ, mainly with symmetrical divisions, and produces substantial morphological changes in the normal SVZ architecture, where we also report the presence of FGFR1 in almost all SVZ cells. Interestingly, for the first time we show FGFR1 expression in the basal body of primary cilia in neural progenitor cells. Additionally, we have found that A1 over-expression also enhances neuroblast motility, mainly through FGFR1 activity. Together, these changes lead to a selective increase in several GABAergic interneuron populations in different OB layers. These specific alterations in the OB would be sufficient to disrupt the normal processing of sensory information and consequently alter olfactory memory. In summary, this work shows that FGFR1-mediated A1 activity plays a crucial role in the continuous remodelling of the adult OB. PMID:25300351

  4. Selenomethionine Ameliorates Neuropathology in the Olfactory Bulb of a Triple Transgenic Mouse Model of Alzheimer’s Disease

    PubMed Central

    Zhang, Zhong-Hao; Chen, Chen; Wu, Qiu-Yan; Zheng, Rui; Chen, Yao; Liu, Qiong; Ni, Jia-Zuan; Song, Guo-Li

    2016-01-01

    Olfactory dysfunction is an early and common symptom in Alzheimer′s disease (AD) and is reported to be related to several pathologic changes, including the deposition of Aβ and hyperphosphorylated tau protein as well as synaptic impairment. Selenomethionine (Se-Met), the major form of selenium in animals and humans, may be a promising therapeutic option for AD as it decreases the deposition of Aβ and tau hyperphosphorylation in a triple transgenic mouse model of AD (3× Tg-AD). In this study, 4-month-old AD mice were treated with 6 µg/mL Se-Met in drinking water for 12 weeks and the effect of Se-Met on neuropathological deficits in olfactory bulb (OB) of 3× Tg-AD mice was investigated. The administration of Se-Met effectively decreased the production and deposition of Aβ by inhibiting β-site amyloid precursor protein cleaving enzyme 1 (BACE1)-regulated amyloid precursor protein (APP) processing and reduced the level of total tau and phosphorylated tau, which depended on depressing the activity and expression of glycogen synthase kinase-3β (GSK-3β) and cyclin-dependent kinase 5 (CDK5). Meanwhile, Se-Met reduced glial activation, relieved neuroinflammation and attenuated neuronal cell death in the OB of AD mice. So Se-Met could improve pathologic changes of AD in the OB, which further demonstrated the potential therapeutic effect of Se-Met in AD. PMID:27689994

  5. Disruption of Kcc2-dependent inhibition of olfactory bulb output neurons suggests its importance in odour discrimination.

    PubMed

    Gödde, Kathrin; Gschwend, Olivier; Puchkov, Dmytro; Pfeffer, Carsten K; Carleton, Alan; Jentsch, Thomas J

    2016-01-01

    Synaptic inhibition in the olfactory bulb (OB), the first relay station of olfactory information, is believed to be important for odour discrimination. We interfered with GABAergic inhibition of mitral and tufted cells (M/T cells), the principal neurons of the OB, by disrupting their potassium-chloride cotransporter 2 (Kcc2). Roughly, 70% of mice died around 3 weeks, but surviving mice appeared normal. In these mice, the resulting increase in the intracellular Cl(-) concentration nearly abolished GABA-induced hyperpolarization of mitral cells (MCs) and unexpectedly increased the number of perisomatic synapses on MCs. In vivo analysis of odorant-induced OB electrical activity revealed increased M/T cell firing rate, altered phasing of action potentials in the breath cycle and disrupted separation of odour-induced M/T cell activity patterns. Mice also demonstrated a severely impaired ability to discriminate chemically similar odorants or odorant mixtures. Our work suggests that precisely tuned GABAergic inhibition onto M/T cells is crucial for M/T cell spike pattern separation needed to distinguish closely similar odours. PMID:27389623

  6. Odor representations in the olfactory bulb evolve after the first breath and persist as an odor afterimage

    PubMed Central

    Patterson, Michael Andrew; Lagier, Samuel; Carleton, Alan

    2013-01-01

    Rodents can discriminate odors in one breath, and mammalian olfaction research has thus focused on the first breath. However, sensory representations dynamically change during and after stimuli. To investigate these dynamics, we recorded spike trains from the olfactory bulb of awake, head-fixed mice and found that some mitral cells’ odor representations changed following the first breath and others continued after odor cessation. Population analysis revealed that these postodor responses contained odor- and concentration-specific information—an odor afterimage. Using calcium imaging, we found that most olfactory glomerular activity was restricted to the odor presentation, implying that the afterimage is not primarily peripheral. The odor afterimage was not dependent on odorant physicochemical properties. To artificially induce aftereffects, we photostimulated mitral cells using channelrhodopsin and recorded centrally maintained persistent activity. The strength and persistence of the afterimage was dependent on the duration of both artificial and natural stimulation. In summary, we show that the odor representation evolves after the first breath and that there is a centrally maintained odor afterimage, similar to other sensory systems. These dynamics may help identify novel odorants in complex environments. PMID:23918364

  7. Disruption of Kcc2-dependent inhibition of olfactory bulb output neurons suggests its importance in odour discrimination

    PubMed Central

    Gödde, Kathrin; Gschwend, Olivier; Puchkov, Dmytro; Pfeffer, Carsten K.; Carleton, Alan; Jentsch, Thomas J.

    2016-01-01

    Synaptic inhibition in the olfactory bulb (OB), the first relay station of olfactory information, is believed to be important for odour discrimination. We interfered with GABAergic inhibition of mitral and tufted cells (M/T cells), the principal neurons of the OB, by disrupting their potassium-chloride cotransporter 2 (Kcc2). Roughly, 70% of mice died around 3 weeks, but surviving mice appeared normal. In these mice, the resulting increase in the intracellular Cl− concentration nearly abolished GABA-induced hyperpolarization of mitral cells (MCs) and unexpectedly increased the number of perisomatic synapses on MCs. In vivo analysis of odorant-induced OB electrical activity revealed increased M/T cell firing rate, altered phasing of action potentials in the breath cycle and disrupted separation of odour-induced M/T cell activity patterns. Mice also demonstrated a severely impaired ability to discriminate chemically similar odorants or odorant mixtures. Our work suggests that precisely tuned GABAergic inhibition onto M/T cells is crucial for M/T cell spike pattern separation needed to distinguish closely similar odours. PMID:27389623

  8. RhoE deficiency alters postnatal subventricular zone development and the number of calbindin-expressing neurons in the olfactory bulb of mouse.

    PubMed

    Ballester-Lurbe, Begoña; González-Granero, Susana; Mocholí, Enric; Poch, Enric; García-Manzanares, María; Dierssen, Mara; Pérez-Roger, Ignacio; García-Verdugo, José M; Guasch, Rosa M; Terrado, José

    2015-11-01

    The subventricular zone represents an important reservoir of progenitor cells in the adult brain. Cells from the subventricular zone migrate along the rostral migratory stream and reach the olfactory bulb, where they originate different types of interneurons. In this work, we have analyzed the role of the small GTPase RhoE/Rnd3 in subventricular zone cell development using mice-lacking RhoE expression. Our results show that RhoE null mice display a remarkable postnatal broadening of the subventricular zone and caudal rostral migratory stream. This broadening was caused by an increase in progenitor proliferation, observed in the second postnatal week but not before, and by an altered migration of the cells, which appeared in disorganized cell arrangements that impaired the appropriate contact between cells in the rostral migratory stream. In addition, the thickness of the granule cell layer in the olfactory bulb was reduced, although the density of granule cells did not differ between wild-type and RhoE null mice. Finally, the lack of RhoE expression affected the olfactory glomeruli inducing a severe reduction of calbindin-expressing interneurons in the periglomerular layer. This was already evident in the newborns and even more pronounced 15 days later when RhoE null mice displayed 89% less cells than control mice. Our results indicate that RhoE has pleiotropic functions on subventricular cells because of its role in proliferation and tangential migration, affecting mainly the development of calbindin-expressing cells in the olfactory bulb.

  9. Sexual Stimulation Increases the Survival of New Cells in the Accessory Olfactory Bulb of the Male Rat

    PubMed Central

    Unda, Nancy M.; Portillo, Wendy; Corona, Rebeca; Paredes, Raúl G.

    2016-01-01

    Sexual behavior in rodents is modulated by the olfactory system. The olfactory bulb (OB) is a structure that undergoes continues neurogenesis in adulthood. We have previously shown that 15 days after males rats pace the sexual interaction and ejaculate 1 or 3 times, there is an increase in the density of new cells that reach the accessory olfactory bulb (AOB). The aim of the present study was to evaluate if sexual behavior in male rats increases the density of new neurons that survive 45 days after sexual behavior in the AOB and in the main OB (MOB). Male rats were randomly divided in four groups: (1) Control (Ctr), males without sexual interaction; (2) Exposed (Exp), males only exposed to a sexually receptive female; (3) No pacing (NP), males that mated in conditions in which the female paced the sexual interaction; (4) One ejaculation (1E), males that paced the sexual interaction with a receptive female and ejaculated once; and (5) Three ejaculations (3E), males that paced the sexual interaction and were allowed to ejaculate three times. All males were injected with the DNA synthesis marker 5-bromo-2-deoxyuridine (BrdU), and were tested in one of the above conditions. 45 days later they were sacrificed, and the OBs were processed to identify new cells and evaluate if they had differentiated into neurons. Our data indicate that males that ejaculated three times showed an increase in the density of new cells that survive in the posterior part of the granular cell layer of the AOB and have more new neurons that the control group. However, no significant differences were found in the percentage of new cells that differentiate into neurons. No significant increase in the density of new cells was observed in the MOB. Our data show that pacing the sexual interaction until three ejaculations increases the density of new cells and neurons in the granular layer of the AOB, confirming that sexual behavior induces long-lasting plastic changes in the OB. PMID:26973447

  10. Sexual Stimulation Increases the Survival of New Cells in the Accessory Olfactory Bulb of the Male Rat.

    PubMed

    Unda, Nancy M; Portillo, Wendy; Corona, Rebeca; Paredes, Raúl G

    2016-01-01

    Sexual behavior in rodents is modulated by the olfactory system. The olfactory bulb (OB) is a structure that undergoes continues neurogenesis in adulthood. We have previously shown that 15 days after males rats pace the sexual interaction and ejaculate 1 or 3 times, there is an increase in the density of new cells that reach the accessory olfactory bulb (AOB). The aim of the present study was to evaluate if sexual behavior in male rats increases the density of new neurons that survive 45 days after sexual behavior in the AOB and in the main OB (MOB). Male rats were randomly divided in four groups: (1) Control (Ctr), males without sexual interaction; (2) Exposed (Exp), males only exposed to a sexually receptive female; (3) No pacing (NP), males that mated in conditions in which the female paced the sexual interaction; (4) One ejaculation (1E), males that paced the sexual interaction with a receptive female and ejaculated once; and (5) Three ejaculations (3E), males that paced the sexual interaction and were allowed to ejaculate three times. All males were injected with the DNA synthesis marker 5-bromo-2-deoxyuridine (BrdU), and were tested in one of the above conditions. 45 days later they were sacrificed, and the OBs were processed to identify new cells and evaluate if they had differentiated into neurons. Our data indicate that males that ejaculated three times showed an increase in the density of new cells that survive in the posterior part of the granular cell layer of the AOB and have more new neurons that the control group. However, no significant differences were found in the percentage of new cells that differentiate into neurons. No significant increase in the density of new cells was observed in the MOB. Our data show that pacing the sexual interaction until three ejaculations increases the density of new cells and neurons in the granular layer of the AOB, confirming that sexual behavior induces long-lasting plastic changes in the OB. PMID:26973447

  11. The type 3 adenylyl cyclase is required for the survival and maturation of newly generated granule cells in the olfactory bulb.

    PubMed

    Luo, Jie; Chen, Xuanmao; Pan, Yung-Wei; Lu, Song; Xia, Zhengui; Storm, Daniel R

    2015-01-01

    The type 3 adenylyl cyclase (AC3) is localized to olfactory cilia in the main olfactory epithelium (MOE) and primary cilia in the adult mouse brain. Although AC3 has been strongly implicated in odor perception and olfactory sensory neuron (OSN) targeting, its role in granule cells (GCs), the most abundant interneurons in the main olfactory bulb (MOB), remains largely unknown. Here, we report that the deletion of AC3 leads to a significant reduction in the size of the MOB as well as the level of adult neurogenesis. The cell proliferation and cell cycle in the subventricular zone (SVZ), however, are not suppressed in AC3-/- mice. Furthermore, AC3 deletion elevates the apoptosis of GCs and disrupts the maturation of newly formed GCs. Collectively, our results identify a fundamental role for AC3 in the development of adult-born GCs in the MOB.

  12. Toxic effects of inhaled manganese on the olfactory bulb: an ultrastructural approach in mice.

    PubMed

    Colin-Barenque, L; Souza-Gallardo, L M; Fortoul, T I

    2011-01-01

    Olfactory dysfunction is a common symptom reported by patients with neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Despite the knowledge gathered about the pathology of these diseases, little information has been generated regarding the ultrastructure modifications of the granule cells that regulate the information for odor identification. Swollen organelles and nuclear invaginations identified the exposed mice. Necrosis was evidenced at 4th week of exposure, whereas apoptosis arose at 8th week of exposure. A ruffled electron-dense membrane changes were also found. The changes observed could be explained by the reactive oxygen species generated by manganese and its effects on the membrane's structure and on the cytoskeleton's function. This study contributes to correlate metal air pollution and neurodegenerative changes with olfactory affection. PMID:20965884

  13. Effects of total saponins of Panax notoginseng on immature neuroblasts in the adult olfactory bulb following global cerebral ischemia/reperfusion.

    PubMed

    He, Xu; Deng, Feng-Jun; Ge, Jin-Wen; Yan, Xiao-Xin; Pan, Ai-Hua; Li, Zhi-Yuan

    2015-09-01

    The main active components extracted from Panax notoginseng are total saponins. They have been shown to inhibit platelet aggregation, increase cerebral blood flow, improve neurological behavior, decrease infarct volume and promote proliferation and differentiation of neural stem cells in the hippocampus and lateral ventricles. However, there is a lack of studies on whether total saponins of Panax notoginseng have potential benefits on immature neuroblasts in the olfactory bulb following ischemia and reperfusion. This study established a rat model of global cerebral ischemia and reperfusion using four-vessel occlusion. Rats were administered total saponins of Panax notoginseng at 75 mg/kg intraperitoneally 30 minutes after ischemia then once a day, for either 7 or 14 days. Total saponins of Panax notoginseng enhanced the number of doublecortin (DCX)(+) neural progenitor cells and increased co-localization of DCX with neuronal nuclei and phosphorylated cAMP response element-binding/DCX(+) neural progenitor cells in the olfactory bulb at 7 and 14 days post ischemia. These findings indicate that following global brain ischemia/reperfusion, total saponins of Panax notoginseng promote differentiation of DCX(+) cells expressing immature neuroblasts in the olfactory bulb and the underlying mechanism is related to the activation of the signaling pathway of cyclic adenosine monophosphate response element binding protein. PMID:26604906

  14. Effects of total saponins of Panax notoginseng on immature neuroblasts in the adult olfactory bulb following global cerebral ischemia/reperfusion

    PubMed Central

    He, Xu; Deng, Feng-jun; Ge, Jin-wen; Yan, Xiao-xin; Pan, Ai-hua; Li, Zhi-yuan

    2015-01-01

    The main active components extracted from Panax notoginseng are total saponins. They have been shown to inhibit platelet aggregation, increase cerebral blood flow, improve neurological behavior, decrease infarct volume and promote proliferation and differentiation of neural stem cells in the hippocampus and lateral ventricles. However, there is a lack of studies on whether total saponins of Panax notoginseng have potential benefits on immature neuroblasts in the olfactory bulb following ischemia and reperfusion. This study established a rat model of global cerebral ischemia and reperfusion using four-vessel occlusion. Rats were administered total saponins of Panax notoginseng at 75 mg/kg intraperitoneally 30 minutes after ischemia then once a day, for either 7 or 14 days. Total saponins of Panax notoginseng enhanced the number of doublecortin (DCX)+ neural progenitor cells and increased co-localization of DCX with neuronal nuclei and phosphorylated cAMP response element-binding/DCX+ neural progenitor cells in the olfactory bulb at 7 and 14 days post ischemia. These findings indicate that following global brain ischemia/reperfusion, total saponins of Panax notoginseng promote differentiation of DCX+ cells expressing immature neuroblasts in the olfactory bulb and the underlying mechanism is related to the activation of the signaling pathway of cyclic adenosine monophosphate response element binding protein. PMID:26604906

  15. Pheromones from males of different familiarity exert divergent effects on adult neurogenesis in the female accessory olfactory bulb.

    PubMed

    Wu, Jyun-Han; Han, Yueh-Ting; Yu, Jenn-Yah; Wang, Tsu-Wei

    2013-08-01

    Pheromones from urine of unfamiliar conspecific male animals can reinitiate a female's estrus cycle to cause pregnancy block through the vomeronasal organ (VNO)-accessory olfactory bulb (AOB)-hypothalamic pathway. This phenomenon is called the Bruce effect. Pheromones from the mate of the female, however, do not trigger re-entrance of the estrus cycle because an olfactory memory toward its mate is formed. The activity of the VNO-AOB-hypothalamic pathway is negatively modulated by GABAergic granule cells in the AOB. Since these cells are constantly replenished by neural stem cells in the subventricular zone (SVZ) of the lateral ventricle throughout adulthood and adult neurogenesis is required for mate recognition and fertility, we tested the hypothesis that pheromones from familiar and unfamiliar males may have different effects on adult AOB neurogenesis in female mice. When female mice were exposed to bedding used by a male or lived with one, cell proliferation and neuroblast production in the SVZ were increased. Furthermore, survival of newly generated cells in the AOB was enhanced. This survival effect was transient and mediated by norepinephrine. Interestingly, male bedding-induced newborn cell survival in the AOB but not cell proliferation in the SVZ was attenuated when females were subjected to bedding from an unfamiliar male. Our results indicate that male pheromones from familiar and unfamiliar males exert different effects on neurogenesis in the adult female AOB. Given that adult neurogenesis is required for reproductive behaviors, these divergent pheromonal effects may provide a mechanism for the Bruce effect. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 73: 632-645, 2013.

  16. Role of intraglomerular circuits in shaping temporally structured responses to naturalistic inhalation-driven sensory input to the olfactory bulb

    PubMed Central

    Carey, Ryan M.; Sherwood, William Erik; Shipley, Michael T.; Borisyuk, Alla

    2015-01-01

    Olfaction in mammals is a dynamic process driven by the inhalation of air through the nasal cavity. Inhalation determines the temporal structure of sensory neuron responses and shapes the neural dynamics underlying central olfactory processing. Inhalation-linked bursts of activity among olfactory bulb (OB) output neurons [mitral/tufted cells (MCs)] are temporally transformed relative to those of sensory neurons. We investigated how OB circuits shape inhalation-driven dynamics in MCs using a modeling approach that was highly constrained by experimental results. First, we constructed models of canonical OB circuits that included mono- and disynaptic feedforward excitation, recurrent inhibition and feedforward inhibition of the MC. We then used experimental data to drive inputs to the models and to tune parameters; inputs were derived from sensory neuron responses during natural odorant sampling (sniffing) in awake rats, and model output was compared with recordings of MC responses to odorants sampled with the same sniff waveforms. This approach allowed us to identify OB circuit features underlying the temporal transformation of sensory inputs into inhalation-linked patterns of MC spike output. We found that realistic input-output transformations can be achieved independently by multiple circuits, including feedforward inhibition with slow onset and decay kinetics and parallel feedforward MC excitation mediated by external tufted cells. We also found that recurrent and feedforward inhibition had differential impacts on MC firing rates and on inhalation-linked response dynamics. These results highlight the importance of investigating neural circuits in a naturalistic context and provide a framework for further explorations of signal processing by OB networks. PMID:25717156

  17. Role of intraglomerular circuits in shaping temporally structured responses to naturalistic inhalation-driven sensory input to the olfactory bulb.

    PubMed

    Carey, Ryan M; Sherwood, William Erik; Shipley, Michael T; Borisyuk, Alla; Wachowiak, Matt

    2015-05-01

    Olfaction in mammals is a dynamic process driven by the inhalation of air through the nasal cavity. Inhalation determines the temporal structure of sensory neuron responses and shapes the neural dynamics underlying central olfactory processing. Inhalation-linked bursts of activity among olfactory bulb (OB) output neurons [mitral/tufted cells (MCs)] are temporally transformed relative to those of sensory neurons. We investigated how OB circuits shape inhalation-driven dynamics in MCs using a modeling approach that was highly constrained by experimental results. First, we constructed models of canonical OB circuits that included mono- and disynaptic feedforward excitation, recurrent inhibition and feedforward inhibition of the MC. We then used experimental data to drive inputs to the models and to tune parameters; inputs were derived from sensory neuron responses during natural odorant sampling (sniffing) in awake rats, and model output was compared with recordings of MC responses to odorants sampled with the same sniff waveforms. This approach allowed us to identify OB circuit features underlying the temporal transformation of sensory inputs into inhalation-linked patterns of MC spike output. We found that realistic input-output transformations can be achieved independently by multiple circuits, including feedforward inhibition with slow onset and decay kinetics and parallel feedforward MC excitation mediated by external tufted cells. We also found that recurrent and feedforward inhibition had differential impacts on MC firing rates and on inhalation-linked response dynamics. These results highlight the importance of investigating neural circuits in a naturalistic context and provide a framework for further explorations of signal processing by OB networks.

  18. Characterization of transgenic zebrafish lines that express GFP in the retina, pineal gland, olfactory bulb, hatching gland, and optic tectum.

    PubMed

    Fang, Wei; Bonaffini, Sarah; Zou, Jian; Wang, Xiaolei; Zhang, Cen; Tsujimura, Taro; Kawamura, Shoji; Wei, Xiangyun

    2013-01-01

    Transgenic animals are powerful tools to study gene function invivo. Here we characterize several transgenic zebrafish lines that express green fluorescent protein (GFP) under the control of the LCR(RH2)-RH2-1 or LCR(RH2)-RH2-2 green opsin regulatory elements. Using confocal immunomicroscopy, stereo-fluorescence microscopy, and Western blotting, we show that the Tg(LCR(RH2)-RH2-1:GFP)(pt112) and Tg(LCR(RH2)-RH2-2:GFP)(pt115) transgenic zebrafish lines express GFP in the pineal gland and certain types of photoreceptors. In addition, some of these lines also express GFP in the hatching gland, optic tectum, or olfactory bulb. Some of the expression patterns differ significantly from previously published similar transgenic fish lines, making them useful tools for studying the development of the corresponding tissues and organs. In addition, the variations of GFP expression among different lines corroborate the notion that transgenic expression is often subjected to position effect, thus emphasizing the need for careful verification of expression patterns when transgenic animal models are utilized for research.

  19. The basal forebrain modulates spontaneous activity of principal cells in the main olfactory bulb of anesthetized mice

    PubMed Central

    Zhan, Xiping; Yin, Pingbo; Heinbockel, Thomas

    2013-01-01

    Spontaneous activity is an important characteristic of the principal cells in the main olfactory bulb (MOB) for encoding odor information, which is modulated by the basal forebrain. Cholinergic activation has been reported to inhibit all major neuron types in the MOB. In this study, the effect of diagonal band (NDB) stimulation on mitral/tufted (M/T) cell spontaneous activity was examined in anesthetized mice. NDB stimulation increased spontaneous activity in 66 MOB neurons which lasted for 2–35 s before returning to the baseline level. The majority of the effected units showed a decrease of interspike intervals (ISI) at a range of 8–25 ms. Fifty-two percent of NDB stimulation responsive units showed intrinsic rhythmical bursting, which was enhanced temporarily by NDB stimulation, whereas the remaining non-rhythmic units were capable of synchronized bursting. The effect was attenuated by scopolamine in 21 of 27 units tested. Only four NDB units were inhibited by NDB stimulation, an inhibition that lasted less than 10 s. The NDB stimulation responsive neurons appeared to be M/T cells. Our findings demonstrate an NDB excitation effect on M/T neurons that mostly requires muscarinic receptor activation, and is likely due to non-selectivity of electrical stimulation. This suggests that cholinergic and a diverse group of non-cholinergic neurons in the basal forebrain co-ordinately modulate the dynamics of M/T cell spontaneous activity, which is fundamental for odor representation and attentional perception. PMID:24065892

  20. The subrhinal paleocortex in the hedgehog tenrec: a multiarchitectonic characterization and an analysis of its connections with the olfactory bulb.

    PubMed

    Künzle, H; Radtke-Schuller, S

    2000-12-01

    In the Madagascan hedgehog tenrec, Echinops telfairi, the entire paleocortical region (PCx) subjacent to the rhinal indentation is composed of three layers and occupies up to two thirds of the lateral hemisphere. A clear differentiation of PCx into its presumed constituents, the piriform cortex and the entorhinal cortex, as seen in other mammals, has not been obtained so far. To gain insight into location and intrinsic organization of these areas in a basal placental mammal we investigated the tenrec's PCx using cyto-, myelo- and chemoarchitectural criteria (zinc, acetylcholinesterase, NADPh-diaphorase, Wisteria floribunda agglutinin, parvalbumin, calbindin, calretinin) and analysed its connections with the olfactory bulb. The layers 2 and 3 of the tenrec's PCx differed from the corresponding layers in the rat. The layer 2 showed a complex distribution of corticobulbar cells but could not be subdivided, in contrast to layer 3. Additional cell groups in the depth of PCx were tentatively compared with subdivisions of the endopiriform region. The architectural and connectional features varied clearly along the rostrocaudal and dorso-ventral extents of PCx and gave hints for the presence of different paleocortical subdivisions. With the possible exception of an area located at the most caudal tip of the dorsomedial hemisphere, however, no conclusive evidence was obtained for the presence of a multilayered, entorhinal region. The bulbar projections to the PCx were very extensive and almost exclusively ipsilateral. The laterality of the projection is similar to that in higher mammals, but differs from that in the erinaceous hedgehog.

  1. Opposite-sex attraction in male mice requires testosterone-dependent regulation of adult olfactory bulb neurogenesis

    PubMed Central

    Schellino, Roberta; Trova, Sara; Cimino, Irene; Farinetti, Alice; Jongbloets, Bart C.; Pasterkamp, R. Jeroen; Panzica, Giancarlo; Giacobini, Paolo; De Marchis, Silvia; Peretto, Paolo

    2016-01-01

    Opposite-sex attraction in most mammals depends on the fine-tuned integration of pheromonal stimuli with gonadal hormones in the brain circuits underlying sexual behaviour. Neural activity in these circuits is regulated by sensory processing in the accessory olfactory bulb (AOB), the first central station of the vomeronasal system. Recent evidence indicates adult neurogenesis in the AOB is involved in sex behaviour; however, the mechanisms underlying this function are unknown. By using Semaphorin 7A knockout (Sema7A ko) mice, which show a reduced number of gonadotropin-releasing-hormone neurons, small testicles and subfertility, and wild-type males castrated during adulthood, we demonstrate that the level of circulating testosterone regulates the sex-specific control of AOB neurogenesis and the vomeronasal system activation, which influences opposite-sex cue preference/attraction in mice. Overall, these data highlight adult neurogenesis as a hub for the integration of pheromonal and hormonal cues that control sex-specific responses in brain circuits. PMID:27782186

  2. Spatial Representations of Odorants in Olfactory Bulbs of Rats and Mice: Similarities and Differences in Chemotopic Organization

    PubMed Central

    Johnson, Brett A.; Xu, Zhe; Ali, Sameera S.; Leon, Michael

    2009-01-01

    In previous studies, we mapped glomerular layer 2-deoxyglucose uptake evoked by hundreds of both systematically related and chemically distinct odorants in rat olfactory bulbs. To determine which principles of chemotopic organization revealed in these studies may be more fundamental and which may be more species-typical, we now have characterized patterns of responses to 30 of these odorants in mice. We found that only a few odorants evoked their multiple foci of peak activity in exactly the same locations in the two species. In mice, as in rats, odorants that shared molecular features evoked overlapping patterns, but the locations of the feature-responsive domains often differed in rats and mice. In rats, increasing carbon number within a homologous series of aliphatic odorants is generally associated with rostral and ventral progressions of activity within domains responding to odorant functional group and/or hydrocarbon backbone. Such chemotopic progressions were not obvious in mice, which instead showed more abrupt differences in activated glomeruli within the domains for odorants differing by a single methylene group. Despite the differences, quantitative relationships between overall uptake patterns exhibited a similar organization with respect to odorant chemistry for the two species, probably due to partial overlaps of peak domains and more extensive overlaps in large, low-activity areas for rats and mice. We conclude that clustering responses to shared odorant features may be a general strategy for odor coding, but that the specific locations of high-activity domains may be unique to a species. PMID:19363812

  3. The effect of spaceflight on mouse olfactory bulb volume, neurogenesis, and cell death indicates the protective effect of novel environment.

    PubMed

    Latchney, Sarah E; Rivera, Phillip D; Mao, Xiao W; Ferguson, Virginia L; Bateman, Ted A; Stodieck, Louis S; Nelson, Gregory A; Eisch, Amelia J

    2014-06-15

    Space missions necessitate physiological and psychological adaptations to environmental factors not present on Earth, some of which present significant risks for the central nervous system (CNS) of crewmembers. One CNS region of interest is the adult olfactory bulb (OB), as OB structure and function are sensitive to environmental- and experience-induced regulation. It is currently unknown how the OB is altered by spaceflight. In this study, we evaluated OB volume and neurogenesis in mice shortly after a 13-day flight on Space Shuttle Atlantis [Space Transport System (STS)-135] relative to two groups of control mice maintained on Earth. Mice housed on Earth in animal enclosure modules that mimicked the conditions onboard STS-135 (AEM-Ground mice) had greater OB volume relative to mice maintained in standard housing on Earth (Vivarium mice), particularly in the granule (GCL) and glomerular (GL) cell layers. AEM-Ground mice also had more OB neuroblasts and fewer apoptotic cells relative to Vivarium mice. However, the AEM-induced increase in OB volume and neurogenesis was not seen in STS-135 mice (AEM-Flight mice), suggesting that spaceflight may have negated the positive effects of the AEM. In fact, when OB volume of AEM-Flight mice was considered, there was a greater density of apoptotic cells relative to AEM-Ground mice. Our findings suggest that factors present during spaceflight have opposing effects on OB size and neurogenesis, and provide insight into potential strategies to preserve OB structure and function during future space missions. PMID:24744382

  4. The effect of spaceflight on mouse olfactory bulb volume, neurogenesis, and cell death indicates the protective effect of novel environment

    PubMed Central

    Latchney, Sarah E.; Rivera, Phillip D.; Mao, Xiao W.; Ferguson, Virginia L.; Bateman, Ted A.; Stodieck, Louis S.; Nelson, Gregory A.

    2014-01-01

    Space missions necessitate physiological and psychological adaptations to environmental factors not present on Earth, some of which present significant risks for the central nervous system (CNS) of crewmembers. One CNS region of interest is the adult olfactory bulb (OB), as OB structure and function are sensitive to environmental- and experience-induced regulation. It is currently unknown how the OB is altered by spaceflight. In this study, we evaluated OB volume and neurogenesis in mice shortly after a 13-day flight on Space Shuttle Atlantis [Space Transport System (STS)-135] relative to two groups of control mice maintained on Earth. Mice housed on Earth in animal enclosure modules that mimicked the conditions onboard STS-135 (AEM-Ground mice) had greater OB volume relative to mice maintained in standard housing on Earth (Vivarium mice), particularly in the granule (GCL) and glomerular (GL) cell layers. AEM-Ground mice also had more OB neuroblasts and fewer apoptotic cells relative to Vivarium mice. However, the AEM-induced increase in OB volume and neurogenesis was not seen in STS-135 mice (AEM-Flight mice), suggesting that spaceflight may have negated the positive effects of the AEM. In fact, when OB volume of AEM-Flight mice was considered, there was a greater density of apoptotic cells relative to AEM-Ground mice. Our findings suggest that factors present during spaceflight have opposing effects on OB size and neurogenesis, and provide insight into potential strategies to preserve OB structure and function during future space missions. PMID:24744382

  5. Granule cell excitability regulates gamma and beta oscillations in a model of the olfactory bulb dendrodendritic microcircuit.

    PubMed

    Osinski, Bolesław L; Kay, Leslie M

    2016-08-01

    Odors evoke gamma (40-100 Hz) and beta (20-30 Hz) oscillations in the local field potential (LFP) of the mammalian olfactory bulb (OB). Gamma (and possibly beta) oscillations arise from interactions in the dendrodendritic microcircuit between excitatory mitral cells (MCs) and inhibitory granule cells (GCs). When cortical descending inputs to the OB are blocked, beta oscillations are extinguished whereas gamma oscillations become larger. Much of this centrifugal input targets inhibitory interneurons in the GC layer and regulates the excitability of GCs, which suggests a causal link between the emergence of beta oscillations and GC excitability. We investigate the effect that GC excitability has on network oscillations in a computational model of the MC-GC dendrodendritic network with Ca(2+)-dependent graded inhibition. Results from our model suggest that when GC excitability is low, the graded inhibitory current mediated by NMDA channels and voltage-dependent Ca(2+) channels (VDCCs) is also low, allowing MC populations to fire in the gamma frequency range. When GC excitability is increased, the activation of NMDA receptors and other VDCCs is also increased, allowing the slow decay time constants of these channels to sustain beta-frequency oscillations. Our model argues that Ca(2+) flow through VDCCs alone could sustain beta oscillations and that the switch between gamma and beta oscillations can be triggered by an increase in the excitability state of a subpopulation of GCs. PMID:27121582

  6. Reduction of rat hippocampal calcium-binding protein following commissural, amygdala, septal, perforant path, and olfactory bulb kindling.

    PubMed

    Baimbridge, K G; Mody, I; Miller, J J

    1985-01-01

    The calcium-binding protein (CaBP) content of the hippocampal formation was determined by radioimmunoassay in control and kindled rats. Kindling of a number of different sites resulted in a reduction in the CaBP content of the hippocampal formation, which was shown immunohistochemically to be restricted to the dentate granule cells and their processes. The maximum decline in CaBP varied with the different kindling sites: perforant path, 33%; commissural path, 32%; septum, 30%; amygdala, 18%; and olfactory bulbs, 15%. There were no changes in the CaBP content of the stimulated areas themselves. In cases where the kindling stimulus was delivered unilaterally (perforant path and amygdala), the maximum decrease in hippocampal CaBP was observed ipsilateral to the site of stimulation when the criterion for full kindling was established (six consecutive stage 5 motor seizures). Further kindling trials were required to produce a similar magnitude decrease in the CaBP content of the contralateral hippocampus. These observations are discussed both in relation to the possible role of CaBP in the establishment of a seizure response to kindling and also as a potential compensatory mechanism that may serve to overcome the epileptogenic effects of kindling.

  7. The effect of spaceflight on mouse olfactory bulb volume, neurogenesis, and cell death indicates the protective effect of novel environment.

    PubMed

    Latchney, Sarah E; Rivera, Phillip D; Mao, Xiao W; Ferguson, Virginia L; Bateman, Ted A; Stodieck, Louis S; Nelson, Gregory A; Eisch, Amelia J

    2014-06-15

    Space missions necessitate physiological and psychological adaptations to environmental factors not present on Earth, some of which present significant risks for the central nervous system (CNS) of crewmembers. One CNS region of interest is the adult olfactory bulb (OB), as OB structure and function are sensitive to environmental- and experience-induced regulation. It is currently unknown how the OB is altered by spaceflight. In this study, we evaluated OB volume and neurogenesis in mice shortly after a 13-day flight on Space Shuttle Atlantis [Space Transport System (STS)-135] relative to two groups of control mice maintained on Earth. Mice housed on Earth in animal enclosure modules that mimicked the conditions onboard STS-135 (AEM-Ground mice) had greater OB volume relative to mice maintained in standard housing on Earth (Vivarium mice), particularly in the granule (GCL) and glomerular (GL) cell layers. AEM-Ground mice also had more OB neuroblasts and fewer apoptotic cells relative to Vivarium mice. However, the AEM-induced increase in OB volume and neurogenesis was not seen in STS-135 mice (AEM-Flight mice), suggesting that spaceflight may have negated the positive effects of the AEM. In fact, when OB volume of AEM-Flight mice was considered, there was a greater density of apoptotic cells relative to AEM-Ground mice. Our findings suggest that factors present during spaceflight have opposing effects on OB size and neurogenesis, and provide insight into potential strategies to preserve OB structure and function during future space missions.

  8. Distinct lateral inhibitory circuits drive parallel processing of sensory information in the mammalian olfactory bulb.

    PubMed

    Geramita, Matthew A; Burton, Shawn D; Urban, Nathan N

    2016-01-01

    Splitting sensory information into parallel pathways is a common strategy in sensory systems. Yet, how circuits in these parallel pathways are composed to maintain or even enhance the encoding of specific stimulus features is poorly understood. Here, we have investigated the parallel pathways formed by mitral and tufted cells of the olfactory system in mice and characterized the emergence of feature selectivity in these cell types via distinct lateral inhibitory circuits. We find differences in activity-dependent lateral inhibition between mitral and tufted cells that likely reflect newly described differences in the activation of deep and superficial granule cells. Simulations show that these circuit-level differences allow mitral and tufted cells to best discriminate odors in separate concentration ranges, indicating that segregating information about different ranges of stimulus intensity may be an important function of these parallel sensory pathways.

  9. Distinct lateral inhibitory circuits drive parallel processing of sensory information in the mammalian olfactory bulb.

    PubMed

    Geramita, Matthew A; Burton, Shawn D; Urban, Nathan N

    2016-01-01

    Splitting sensory information into parallel pathways is a common strategy in sensory systems. Yet, how circuits in these parallel pathways are composed to maintain or even enhance the encoding of specific stimulus features is poorly understood. Here, we have investigated the parallel pathways formed by mitral and tufted cells of the olfactory system in mice and characterized the emergence of feature selectivity in these cell types via distinct lateral inhibitory circuits. We find differences in activity-dependent lateral inhibition between mitral and tufted cells that likely reflect newly described differences in the activation of deep and superficial granule cells. Simulations show that these circuit-level differences allow mitral and tufted cells to best discriminate odors in separate concentration ranges, indicating that segregating information about different ranges of stimulus intensity may be an important function of these parallel sensory pathways. PMID:27351103

  10. Distinct lateral inhibitory circuits drive parallel processing of sensory information in the mammalian olfactory bulb

    PubMed Central

    Geramita, Matthew A; Burton, Shawn D; Urban, Nathan N

    2016-01-01

    Splitting sensory information into parallel pathways is a common strategy in sensory systems. Yet, how circuits in these parallel pathways are composed to maintain or even enhance the encoding of specific stimulus features is poorly understood. Here, we have investigated the parallel pathways formed by mitral and tufted cells of the olfactory system in mice and characterized the emergence of feature selectivity in these cell types via distinct lateral inhibitory circuits. We find differences in activity-dependent lateral inhibition between mitral and tufted cells that likely reflect newly described differences in the activation of deep and superficial granule cells. Simulations show that these circuit-level differences allow mitral and tufted cells to best discriminate odors in separate concentration ranges, indicating that segregating information about different ranges of stimulus intensity may be an important function of these parallel sensory pathways. DOI: http://dx.doi.org/10.7554/eLife.16039.001 PMID:27351103

  11. Olfactory bulb removal: effects on sexual behavior and partner-preference in male rats.

    PubMed

    Edwards, D A; Griffis, K T; Tardivel, C

    1990-09-01

    Control and bilaterally bulbectomized male rats were tested in an arena where the male could choose to spend time with (and mate with) a sexually receptive female, a nonreceptive female, or be in a neutral compartment. Control males mated with, and showed a strong preference for, sexually receptive females. Bulbectomy virtually eliminated mating. In addition, bulbectomized males showed no preference for a receptive female over a nonreceptive female, and spent their time equally between the receptive female, the nonreceptive female, and the neutral compartment. Effects of bulbectomy on preference and copulation could be consequences of a severely impaired ability to smell--the perception of odors may be essential for sexual arousal, or the absence of preference and copulation after bulbectomy might reflect a deficit in the male's ability to make odor-dependent classification of conspecifics as appropriate sexual partners. Or the behavioral effects of bulbectomy might reflect a disruption of tonic input to the forebrain that has little or nothing to do with the sensory impairment that follows bulb removal. But whatever the reason, in partner-preference tests bulbectomized males show a striking indifference to the sexual status of females, and it seems likely that the failure to mate is causally linked to this effect of surgery.

  12. Main and accessory olfactory bulbs and their projections in the brain anticipate feeding in food-entrained rats.

    PubMed

    Caba, Mario; Pabello, Marcela; Moreno, Maria Luisa; Meza, Enrique

    2014-10-01

    The olfactory bulb (OB) has a circadian clock independent of the suprachiasmatic nucleus, but very little is known about the functional significance of its oscillations. The OB plays a major role in food intake as it contributes to the evaluation of the hedonic properties of food, it is necessary for a normal pattern of locomotor behavior and their ablation disrupts feeding patterns. Previously we demonstrated that OB of rabbit pups can be entrained by periodic nursing but it was not clear whether food was the entraining signal. Here we hypothesized that OB can be entrained by a food pulse during the day in adult rats under a restricted feeding schedule. Then we expect that OB will have a high activation before food presentation when animals show food anticipatory activity (FAA). To this aim we determined by immunohistochemistry the expression of FOS protein, as an indicator of neural activation, in the mitral and granular cell layers of the main and accessory OB. Additionally we also explored two of the OB brain targets, the piriform cortex (PC) and bed nuclei of the accessory olfactory tract (BAOT), in three groups: ad libitum (ALF), restricted feeding (RF), and fasted rats after restricted feeding (RF-F). In ALF group FOS levels in both main and accessory OB were low during the day and high during the night at the normal onset of the increase of activity, in agreement with previous reports. On the contrary in RF and RF-F groups FOS was high at the time of FAA, just before food presentation, when animals are in a state of high arousal and during food consumption but was low during the night. In their brain targets, we observed a similar pattern as OB in all groups with the only difference being that FOS levels remained high during the night in RF-F group. We conclude that the OB is entrained by food restriction by showing high activation at the time of food presentation, which persists during fasting and impose a similar FOS pattern to the two brain targets

  13. A possible functional necklace formed by placental antigen X-P2-immunoreactive and intensely acetylcholinesterase-reactive (PAX/IAE) glomerular complexes in the rat olfactory bulb.

    PubMed

    Shinoda, K; Ohtsuki, T; Nagano, M; Okumura, T

    1993-07-30

    The relationship between placental antigen X-P2 (PAX)-immunoreactive glomeruli and intensely acetylcholinesterase-reactive (IAE) patchy regions was evaluated by comparison of neighboring cryostat sections of the rat olfactory bulb. Both groups of distribution show similar necklace patterns. Each IAE region consists of heterologous glomerulus-like structures with variable acetylcholinesterase reactivity: strongly and less-reactive (IAE-S and IAE-L) structures. The PAX-immunoreactive glomeruli were detected as parts of the IAE-L portions. Three heterologous PAX/IAE glomeruli or glomerulus-like structures (IAE-S, IAE-L/PAX and IAE-L/non-PAX structures) locally form a distinct glomerular complex, the 'PAX/IAE glomerular complex'. At the caudal end of the main olfactory bulb, nine to sixteen such complexes occur at intervals and form a circumferential 'necklace'. Since one of them corresponds to the 'modified glomerular complex' involved in rat suckling behavior, the entire 'necklace' may be associated with processing olfactory stimuli eliciting or suppressing the suckling response.

  14. Shared and differential traits in the accessory olfactory bulb of caviomorph rodents with particular reference to the semiaquatic capybara.

    PubMed

    Suárez, Rodrigo; Santibáñez, Rodrigo; Parra, Daniela; Coppi, Antonio A; Abrahão, Luciana M B; Sasahara, Tais H C; Mpodozis, Jorge

    2011-05-01

    The vomeronasal system is crucial for social and sexual communication in mammals. Two populations of vomeronasal sensory neurons, each expressing Gαi2 or Gαo proteins, send projections to glomeruli of the rostral or caudal accessory olfactory bulb, rAOB and cAOB, respectively. In rodents, the Gαi2- and Gαo-expressing vomeronasal pathways have shown differential responses to small/volatile vs. large/non-volatile semiochemicals, respectively. Moreover, early gene expression suggests predominant activation of rAOB and cAOB neurons in sexual vs. aggressive contexts, respectively. We recently described the AOB of Octodon degus, a semiarid-inhabiting diurnal caviomorph. Their AOB has a cell indentation between subdomains and the rAOB is twice the size of the cAOB. Moreover, their AOB receives innervation from the lateral aspect, contrasting with the medial innervation of all other mammals examined to date. Aiming to relate AOB anatomy with lifestyle, we performed a morphometric study on the AOB of the capybara, a semiaquatic caviomorph whose lifestyle differs remarkably from that of O. degus. Capybaras mate in water and scent-mark their surroundings with oily deposits, mostly for male-male communication. We found that, similar to O. degus, the AOB of capybaras shows a lateral innervation of the vomeronasal nerve, a cell indentation between subdomains and heterogeneous subdomains, but in contrast to O. degus the caudal portion is larger than the rostral one. We also observed that four other caviomorph species present a lateral AOB innervation and a cell indentation between AOB subdomains, suggesting that those traits could represent apomorphies of the group. We propose that although some AOB traits may be phylogenetically conserved in caviomorphs, ecological specializations may play an important role in shaping the AOB.

  15. Changes in Olfactory Bulb Volume in Parkinson’s Disease: A Systematic Review and Meta-Analysis

    PubMed Central

    Li, Jia; Gu, Cheng-zhi; Su, Jian-bin; Zhu, Lian-hai; Zhou, Yong; Huang, Huai-yu; Liu, Chun-feng

    2016-01-01

    Objective The changes in olfactory bulb (OB) volume in Parkinson’s disease (PD) patients have not yet been comprehensively evaluated. The purpose of this meta-analysis was to explore whether the OB volume was significantly different between PD patients and healthy controls. Methods PubMed and Embase were searched up to March 6, 2015 with no language restrictions. Two independent reviewers screened eligible studies and extracted data on study characteristics and OB volume. Additionally, a systematic review and meta-analysis using a random-effects model were conducted. Publication bias was determined by using funnel plots and Begg’s and Egger’s tests. Subgroup analyses were performed to assess possible sources of heterogeneity. Results Six original case-control studies of 216 PD patients and 175 healthy controls were analyzed. The pooled weighted mean difference (WMD) in the OB volume between the PD patients and the healthy participants was -8.071 for the right OB and -10.124 for the left OB; these values indicated a significant difference among PD patients compared with healthy controls. In addition, a significant difference in the lateralized OB volume was observed in PD patients, with a pooled WMD of 1.618; these results indicated a larger right OB volume than left OB volume in PD patients. In contrast, no difference in the lateralized OB volume was found in healthy controls. No statistical evidence of publication bias among studies was found based on Egger’s or Begg’s tests. Sensitivity analyses revealed that the results were consistent and robust. Conclusions Overall, both the left and the right OB volume were significantly smaller in PD patients than in healthy controls. However, significant heterogeneity and an insufficient number of studies underscore the need for further observational research. PMID:26900958

  16. Compensation of depleted neuronal subsets by new neurons in a local area of the adult olfactory bulb.

    PubMed

    Murata, Koshi; Imai, Maki; Nakanishi, Shigetada; Watanabe, Dai; Pastan, Ira; Kobayashi, Kazuto; Nihira, Tomoko; Mochizuki, Hideki; Yamada, Shuichi; Mori, Kensaku; Yamaguchi, Masahiro

    2011-07-20

    In the olfactory bulb (OB), loss of preexisting granule cells (GCs) and incorporation of adult-born new GCs continues throughout life. GCs consist of distinct subsets. Here, we examined whether the loss and incorporation of GC subsets are coordinated in the OB. We classified GCs into mGluR2-expressing and -negative subsets and selectively ablated mGluR2-expressing GCs in a local area of the OB with immunotoxin-mediated cell ablation method. The density of mGluR2-expressing GCs showed considerable recovery within several weeks after the ablation. During recovery, an mGluR2-expressing new GC subset was preferentially incorporated over an mGluR2-negative new GC subset in the area of ablation, whereas the preferential incorporation was not observed in the intact area. The area-specific preferential incorporation of mGluR2-expressing new GCs occurred for BrdU analog- and retrovirus-labeled adult-born cells as well as for neonate-derived transplanted cells. The mGluR2-expressing new GCs in the ablated area were synaptically incorporated into the local bulbar circuit. The spine size of mGluR2-expressing new GCs in the ablated area was larger than that of those in the intact area. In contrast, mGluR2-negative new GCs did not show ablated area-specific spine enlargement. These results indicate that local OB areas have a mechanism to coordinate the loss and incorporation of GC subsets by compensatory incorporation of new GC subsets, which involves subset-specific cellular incorporation and subset-specific regulation of spine size.

  17. Global Histone H4 Acetylation in the Olfactory Bulb of Lactating Rats with Different Patterns of Maternal Behavior.

    PubMed

    de Moura, Ana Carolina; da Silva, Ivy Reichert Vital; Reinaldo, Gustavo; Dani, Caroline; Elsner, Viviane Rostirola; Giovenardi, Márcia

    2016-10-01

    In rats, variations in the levels of neuromodulatory molecules and in the expression of their receptors are observed during pregnancy and postpartum. These changes may contribute to the development and management of maternal behavior. The frequency of licking the pups is used to evaluate maternal care, having mothers with low licking (LL) and high licking (HL) frequencies. Previously, we found that HL had increased levels of transcriptional expression of the receptors for serotonin (HTR1a, HTR1b), estrogen (Erα), dopamine (D1a), and prolactin (Prlr) than LL in the olfactory bulb (OB); however, the molecular mechanisms behind this phenomenon are unknown. Since evidences pointed out that epigenetic marks, which may alter gene expression, are modulated by environmental factors such as exercise, diet, maternal care, and xenobiotic exposure, our objective was to verify the acetylation levels of histone-H4 in the OB of LL and HL rats. Maternal behavior was studied for the first 7 postpartum days. LL (n = 4) and HL (n = 5) mothers were selected according to the behavior of licking their pups. Acetylation levels of histone-H4 were determined using the Global Histone-H4 Acetylation Assay Kit and expressed as ng/mg protein (mean ± SD). Analysis revealed that HL (278.36 ± 68.95) had increased H4 acetylation levels than LL (183.24 ± 73.05; p = 0.045). The enhanced expression of the previously studied receptors in the OB could be related, at least in part, to the hyperacetylation status of histone-H4 here observed. Afterward, the modulation of histone acetylation levels could exert a pivotal role through molecular mechanisms involved in the different patterns of maternal behavior.

  18. Shared and differential traits in the accessory olfactory bulb of caviomorph rodents with particular reference to the semiaquatic capybara

    PubMed Central

    Suárez, Rodrigo; Santibáñez, Rodrigo; Parra, Daniela; Coppi, Antonio A; Abrahão, Luciana M B; Sasahara, Tais H C; Mpodozis, Jorge

    2011-01-01

    The vomeronasal system is crucial for social and sexual communication in mammals. Two populations of vomeronasal sensory neurons, each expressing Gαi2 or Gαo proteins, send projections to glomeruli of the rostral or caudal accessory olfactory bulb, rAOB and cAOB, respectively. In rodents, the Gαi2- and Gαo-expressing vomeronasal pathways have shown differential responses to small/volatile vs. large/non-volatile semiochemicals, respectively. Moreover, early gene expression suggests predominant activation of rAOB and cAOB neurons in sexual vs. aggressive contexts, respectively. We recently described the AOB of Octodon degus, a semiarid-inhabiting diurnal caviomorph. Their AOB has a cell indentation between subdomains and the rAOB is twice the size of the cAOB. Moreover, their AOB receives innervation from the lateral aspect, contrasting with the medial innervation of all other mammals examined to date. Aiming to relate AOB anatomy with lifestyle, we performed a morphometric study on the AOB of the capybara, a semiaquatic caviomorph whose lifestyle differs remarkably from that of O. degus. Capybaras mate in water and scent-mark their surroundings with oily deposits, mostly for male–male communication. We found that, similar to O. degus, the AOB of capybaras shows a lateral innervation of the vomeronasal nerve, a cell indentation between subdomains and heterogeneous subdomains, but in contrast to O. degus the caudal portion is larger than the rostral one. We also observed that four other caviomorph species present a lateral AOB innervation and a cell indentation between AOB subdomains, suggesting that those traits could represent apomorphies of the group. We propose that although some AOB traits may be phylogenetically conserved in caviomorphs, ecological specializations may play an important role in shaping the AOB. PMID:21457258

  19. Dynamic development of the first synapse impinging on adult-born neurons in the olfactory bulb circuit.

    PubMed

    Katagiri, Hiroyuki; Pallotto, Marta; Nissant, Antoine; Murray, Kerren; Sassoè-Pognetto, Marco; Lledo, Pierre-Marie

    2011-02-01

    The olfactory bulb (OB) receives and integrates newborn interneurons throughout life. This process is important for the proper functioning of the OB circuit and consequently, for the sense of smell. Although we know how these new interneurons are produced, the way in which they integrate into the pre-existing ongoing circuits remains poorly documented. Bearing in mind that glutamatergic inputs onto local OB interneurons are crucial for adjusting the level of bulbar inhibition, it is important to characterize when and how these inputs from excitatory synapses develop on newborn OB interneurons. We studied early synaptic events that lead to the formation and maturation of the first glutamatergic synapses on adult-born granule cells (GCs), the most abundant subtype of OB interneuron. Patch-clamp recordings and electron microscopy (EM) analysis were performed on adult-born interneurons shortly after their arrival in the adult OB circuits. We found that both the ratio of N-methyl-D-aspartate receptor (NMDAR) to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), and the number of functional release sites at proximal inputs reached a maximum during the critical period for the sensory-dependent survival of newborn cells, well before the completion of dendritic arborization. EM analysis showed an accompanying change in postsynaptic density shape during the same period of time. Interestingly, the latter morphological changes disappeared in more mature newly-formed neurons, when the NMDAR to AMPAR ratio had decreased and functional presynaptic terminals expressed only single release sites. Together, these findings show that the first glutamatergic inputs to adult-generated OB interneurons undergo a unique sequence of maturation stages.

  20. Nectin-1 spots as a novel adhesion apparatus that tethers mitral cell lateral dendrites in a dendritic meshwork structure of the developing mouse olfactory bulb.

    PubMed

    Inoue, Takahito; Fujiwara, Takeshi; Rikitake, Yoshiyuki; Maruo, Tomohiko; Mandai, Kenji; Kimura, Kazushi; Kayahara, Tetsuro; Wang, Shujie; Itoh, Yu; Sai, Kousyoku; Mori, Masahiro; Mori, Kensaku; Mizoguchi, Akira; Takai, Yoshimi

    2015-08-15

    Mitral cells project lateral dendrites that contact the lateral and primary dendrites of other mitral cells and granule cell dendrites in the external plexiform layer (EPL) of the olfactory bulb. These dendritic structures are critical for odor information processing, but it remains unknown how they are formed. In immunofluorescence microscopy, the immunofluorescence signal for the cell adhesion molecule nectin-1 was concentrated on mitral cell lateral dendrites in the EPL of the developing mouse olfactory bulb. In electron microscopy, the immunogold particles for nectin-1 were symmetrically localized on the plasma membranes at the contacts between mitral cell lateral dendrites, which showed bilateral darkening without dense cytoskeletal undercoats characteristic of puncta adherentia junctions. We named the contacts where the immunogold particles for nectin-1 were symmetrically accumulated "nectin-1 spots." The nectin-1 spots were 0.21 μm in length on average and the distance between the plasma membranes was 20.8 nm on average. In 3D reconstruction of serial sections, clusters of the nectin-1 spots formed a disc-like structure. In the mitral cell lateral dendrites of nectin-1-knockout mice, the immunogold particles for nectin-1 were undetectable and the plasma membrane darkening was electron-microscopically normalized, but the plasma membranes were partly separated from each other. The nectin-1 spots were further identified between mitral cell lateral and primary dendrites and between mitral cell lateral dendrites and granule cell dendritic spine necks. These results indicate that the nectin-1 spots constitute a novel adhesion apparatus that tethers mitral cell dendrites in a dendritic meshwork structure of the developing mouse olfactory bulb.

  1. The involvement of the olfactory bulbs in the regulation of gonadal and thyroidal activities of male red-winged blackbirds, exposed to short-day light regime.

    PubMed

    Robinzon, B; Katz, Y; Rogers, J G

    1979-01-01

    Surgical removal of the olfactory bulbs (OB) was performed in mature male red-winged blackbirds, maintained under a short-day light regime. Bulbectomy caused hyperphagia, which was not accompanied by obesity. Bulbectomized (OBX) birds had incresaed thyroid follicular activity and had greater developed testes than sham-operated controls. In the adenohypophyses of the OB-removed birds there was an increase in the populations of 4 types of chromophils: alcianophils, PAS-positive basophils, orangeophils and PAS-positive acidophils. The possibility that the OB are involved in the photoperiodic regulation of the activity of the gonads and thyroids is discussed.

  2. A physiological increase of insulin in the olfactory bulb decreases detection of a learned aversive odor and abolishes food odor-induced sniffing behavior in rats.

    PubMed

    Aimé, Pascaline; Hegoburu, Chloé; Jaillard, Tristan; Degletagne, Cyril; Garcia, Samuel; Messaoudi, Belkacem; Thevenet, Marc; Lorsignol, Anne; Duchamp, Claude; Mouly, Anne-Marie; Julliard, Andrée Karyn

    2012-01-01

    Insulin is involved in multiple regulatory mechanisms, including body weight and food intake, and plays a critical role in metabolic disorders such as obesity and diabetes. An increasing body of evidence indicates that insulin is also involved in the modulation of olfactory function. The olfactory bulb (OB) contains the highest level of insulin and insulin receptors (IRs) in the brain. However, a role for insulin in odor detection and sniffing behavior remains to be elucidated. Using a behavioral paradigm based on conditioned olfactory aversion (COA) to isoamyl-acetate odor, we demonstrated that an intracerebroventricular (ICV) injection of 14 mU insulin acutely decreased olfactory detection of fasted rats to the level observed in satiated animals. In addition, whereas fasted animals demonstrated an increase in respiratory frequency upon food odor detection, this effect was absent in fasted animals receiving a 14 mU insulin ICV injection as well as in satiated animals. In parallel, we showed that the OB and plasma insulin levels were increased in satiated rats compared to fasted rats, and that a 14 mU insulin ICV injection elevated the OB insulin level of fasted rats to that of satiated rats. We further quantified insulin receptors (IRs) distribution and showed that IRs are preferentially expressed in the caudal and lateral parts of the main OB, with the highest labeling found in the mitral cells, the main OB projection neurons. Together, these data suggest that insulin acts on the OB network to modulate olfactory processing and demonstrate that olfactory function is under the control of signals involved in energy homeostasis regulation and feeding behaviors. PMID:23251461

  3. Histamine H₃ receptors modulate depolarization-evoked [³H]-noradrenaline release from rat olfactory bulb slices.

    PubMed

    Aquino-Miranda, Guillermo; Osorio-Espinoza, Angélica; Escamilla-Sánchez, Juan; González-Pantoja, Raúl; Ortiz, Jordi; Arias-Montaño, José-Antonio

    2012-02-01

    We have studied the effect of histamine H(3) receptor (H(3)R) activation on the depolarization-evoked release of labeled neurotransmitters from slices of the rat olfactory bulb (rOB). The presence of pre-synaptic H(3)Rs was evidenced by the specific binding of the H(3)R ligand N-α-[methyl-(3)H]histamine to membranes from rOB synaptosomes (maximum binding, B(max), 106 ± 19 fmol/mg protein; dissociation constant, K(d), 0.68 ± 0.11 nM) which was inhibited by selective H(3)R ligands (immepip, (R)(-)-α-methylhistamine (RAMH) and clobenpropit) with affinities similar to those previously reported for H(3)Rs expressed in other rat brain areas. Perfusion of rOB slices with the selective H(3)R agonist RAMH (0.1 and 1 μM) had no effect on the release of [(3)H]-γ-aminobutyric acid ([(3)H]-GABA), [(3)H]-d-aspartate, [(3)H]-dopamine or [(3)H]-5-hydroxytryptamine ([(3)H]-5-HT) evoked by depolarization with high K(+) (20 or 40 mM). [(3)H]-Noradrenaline release induced by 20 mM K(+) was reduced in a modest but significant manner by RAMH (94.9 ± 1.7% and 83.1 ± 2.1% of control release at 0.1 and 1 μM, respectively). The effect of 1 μM RAMH was blocked by the selective H(3)R antagonist/inverse agonist clobenpropit (5 μM). When tested alone clobenpropit and a second H(3)R antagonist/inverse agonist, ciproxifan (both at 1 μM) significantly increased K(+)-evoked [(3)H]-noradrenaline release to 119.4 ± 4.2% and 120.0 ± 3.7% of K(+) alone, respectively. Ciproxifan (1 μM) had no effect on the depolarization-evoked release of the other labeled neurotransmitters. These data indicate that H(3)Rs with constitutive activity modulate noradrenaline release in rOB, presumably through a pre-synaptic action. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.

  4. Acute Immobilization Stress Modulate GABA Release from Rat Olfactory Bulb: Involvement of Endocannabinoids—Cannabinoids and Acute Stress Modulate GABA Release

    PubMed Central

    Delgado, Alejandra; Jaffé, Erica H.

    2011-01-01

    We studied the effects of cannabinoids and acute immobilization stress on the regulation of GABA release in the olfactory bulb. Glutamate-stimulated 3H-GABA release was measured in superfused slices. We report that cannabinoids as WIN55, 212-2, methanandamide, and 2-arachidonoylglycerol were able to inhibit glutamate- and KCl-stimulated 3H-GABA release. This effect was blocked by the CB1 antagonist AM281. On the other hand, acute stress was able per se to increase endocannabinoid activity. This effect was evident since the inhibition of stimulated GABA release by acute stress was reversed with AM281 and tetrahydrolipstatin. Inhibition of the endocannabinoid transport or its catabolism showed reduction of GABA release, antagonized by AM281 in control and stressed animals. These results point to endocannabinoids as inhibitory modulators of GABA release in the olfactory bulb acting through an autocrine mechanism. Apparently, stress increases the endocannabinoid system, modulating GABAergic synaptic function in a primary sensory organ. PMID:21785597

  5. Effects of the alpha 2-adrenoreceptor antagonist dexefaroxan on neurogenesis in the olfactory bulb of the adult rat in vivo: selective protection against neuronal death.

    PubMed

    Bauer, S; Moyse, E; Jourdan, F; Colpaert, F; Martel, J C; Marien, M

    2003-01-01

    A dysfunction of noradrenergic mechanisms originating in the locus coeruleus has been hypothesised to be the critical factor underlying the evolution of central neurodegenerative diseases [Colpaert FC (1994) Noradrenergic mechanism Parkinson's disease: a theory. In: Noradrenergic mechanisms in Parkinson's disease (Briley M, Marien M, eds) pp 225-254. Boca Raton, FL, USA: CRC Press Inc.]. alpha(2)-Adrenoceptor antagonists, presumably in part by facilitating central noradrenergic transmission, afford neuroprotection in vivo in models of cerebral ischaemia, excitotoxicity and devascularization-induced neurodegeneration. The present study utilised the rat olfactory bulb as a model system for examining the effects of the selective alpha(2)-adrenoceptor antagonist dexefaroxan upon determinants of neurogenesis (proliferation, survival and death) in the adult brain in vivo. Cell proliferation (5-bromo-2'-deoxyuridine labelling) and cell death associated with DNA fragmentation (terminal dideoxynucleotidyl transferase-catalysed 2'-deoxyuridine-5'-triphosphate nick end-labelling assay) were quantified following a 7-day treatment with either vehicle or dexefaroxan (0.63 mg/kg i.p., three times daily), followed by a 3-day washout period. The number of terminal dideoxynucleotidyl transferase-catalysed 2'-deoxyuridine-5'-triphosphate nick end-labelling-positive nuclei in the olfactory bulb was lower in dexefaroxan-treated rats, this difference being greatest and significant in the subependymal layer (-52%). In contrast, 5-bromo-2'-deoxyuridine-immunoreactive nuclei were more numerous (+68%) in the bulbs of dexefaroxan-treated rats whilst no differences were detected in the proliferating region of the subventricular zone. Terminal dideoxynucleotidyl transferase-catalysed 2'-deoxyuridine-5'-triphosphate nick end-labelling combination with glial fibrillary acidic protein or neuronal-specific antigen immunohistochemistry revealed that terminal dideoxynucleotidyl transferase

  6. Multiplex assessment of the positions of odorant receptor-specific glomeruli in the mouse olfactory bulb by serial two-photon tomography.

    PubMed

    Zapiec, Bolek; Mombaerts, Peter

    2015-10-27

    In the mouse, axons of olfactory sensory neurons (OSNs) that express the same odorant receptor (OR) gene coalesce into one or a few glomeruli in the olfactory bulb. The positions of OR-specific glomeruli are traditionally described as stereotyped. Here, we have assessed quantitatively the positions of OR-specific glomeruli using serial two-photon tomography, an automated method for whole-organ fluorescence imaging that integrates two-photon microscopy with serial microtome sectioning. Our strategy is multiplexed. By repeated crossing, we generated two strains of mice with gene-targeted mutations at four or five OR loci for a total of six ORs: MOR23 (Olfr16), mOR37A (Olfr155), M72 (Olfr160), P2 (Olfr17), MOR256-17 (Olfr15), and MOR28 (Olfr1507). Glomerular imaging relied on intrinsic fluorescence of GFP or DsRed, or on whole-mount immunofluorescence with antibodies against GFP, DsRed, or β-gal using the method of immunolabeling-enabled three-dimensional imaging of solvent-cleared organs (iDISCO). The high-resolution 3D-reconstructed datasets were segmented to identify the labeled glomeruli and to assess glomerular positional variability between the bulbs of one mouse (intraindividual) and among the bulbs of different mice (interindividual). In 26 mice aged 21 or 50 d or 10 wk, we made measurements of the positions of 352 glomeruli. We find that positional variability of glomeruli correlates with the OR: For instance, the medial MOR28 glomerular domain occupies a surface area that is an order of magnitude larger than the surface area of the medial MOR23 glomerular domain. Our results quantify the level of precision that is delivered by the mechanisms of OSN axon wiring, differentially for the various OSN populations expressing distinct OR genes. PMID:26450880

  7. Differential plasticity of microglial cells in the rostrocaudal neuraxis of the accessory olfactory bulb of female mice following mating and stud male exposure.

    PubMed

    Okere, Chuma O

    2012-04-11

    The formation of an olfactory recognition memory by female mice for the stud male pheromones requires two fundamental conditions: incidence of mating and retention of the stud male with the female for a critical 6h interval following mating. This biologically critical recognition memory results from plasticity of reciprocal dendrodendritic synapses in the accessory olfactory bulb (AOB). In this study, a microglia marker antibody (ionized calcium-binding adaptor protein, Iba1) was used to determine how mating and stud pheromones affect microglia in the AOB rostrocaudal axis in female mice. The results showed that compared with estrus and mating only, mating and pheromone exposure significantly increased Iba1 immunoreactivity in the AOB evidenced by increased complexity of ramified microglial processes characteristic of resting microglial morphological phenotype, particularly in the rostral AOB. The density of Iba1 staining after mating and stud pheromone exposure was higher in the rostral - compared to caudal - AOB and was most prevalent in the external plexiform layer, the site of reciprocal mitral-granule dendrodendritic synapses. While cells with activated phenotype were observed in caudal AOB during estrus, mating/pheromone exposure appeared to induce a morphological transformation to the resting microglia phenotype. Since previous evidence implicate the rostral AOB in processing pheromonal signals and microglial cells monitor active synapses, these observations have important functional implications for a potential role for microglia in processing pheromonal signals in the AOB during the formation of olfactory memory.

  8. Thermally reduced graphene is a permissive material for neurons and astrocytes and de novo neurogenesis in the adult olfactory bulb in vivo.

    PubMed

    Defteralı, Çağla; Verdejo, Raquel; Peponi, Laura; Martín, Eduardo D; Martínez-Murillo, Ricardo; López-Manchado, Miguel Ángel; Vicario-Abejón, Carlos

    2016-03-01

    Graphene and graphene-based nanomaterials (GBNs) are being investigated as potential substrates for the growth of neural stem cells (NSCs), neurons and glia in cell culture models. In contrast, reports testing the effects of graphene directly with adult neural cells in vivo are missing. Here we studied the biocompatibility of thermally reduced graphene (TRG) with neurons and glia, as well as with the generation of new neurons in the adult brain in vivo. TRG injected in the brain together with a retroviral vector expressing GFP to label dividing progenitor cells in the core of the adult olfactory bulb (OB) did not alter de novo neurogenesis, neuronal and astrocyte survival nor did it produce a microglial response. These findings indicate that TRG may be a biocompatible material with neuronal and glial cells in vivo and support its use in studies of brain repair and function. PMID:26751821

  9. Long-term in vivo single-cell tracking reveals the switch of migration patterns in adult-born juxtaglomerular cells of the mouse olfactory bulb.

    PubMed

    Liang, Yajie; Li, Kaizhen; Riecken, Kristoffer; Maslyukov, Anatoliy; Gomez-Nicola, Diego; Kovalchuk, Yury; Fehse, Boris; Garaschuk, Olga

    2016-07-01

    The behavior of adult-born cells can be easily monitored in cell culture or in lower model organisms, but longitudinal observation of individual mammalian adult-born cells in their native microenvironment still proves to be a challenge. Here we have established an approach named optical cell positioning system for long-term in vivo single-cell tracking, which integrates red-green-blue cell labeling with repeated angiography. By combining this approach with in vivo two-photon imaging technique, we characterized the in vivo migration patterns of adult-born neurons in the olfactory bulb. In contrast to the traditional view of mere radial migration of adult-born cells within the bulb, we found that juxtaglomerular cells switch from radial migration to long distance lateral migration upon arrival in their destination layer. This unique long-distance lateral migration has characteristic temporal (stop-and-go) and spatial (migratory, unidirectional or multidirectional) patterns, with a clear cell age-dependent decrease in the migration speed. The active migration of adult-born cells coincides with the time period of initial fate determination and is likely to impact on the integration sites of adult-born cells, their odor responsiveness, as well as their survival rate.

  10. Accelerated Shedding of Prions following Damage to the Olfactory Epithelium

    PubMed Central

    Wilham, Jason M.; Lowe, Diana; Watschke, Christopher P.; Shearin, Harold; Martinka, Scott; Caughey, Byron; Wiley, James A.

    2012-01-01

    In this study, we investigated the role of damage to the nasal mucosa in the shedding of prions into nasal samples as a pathway for prion transmission. Here, we demonstrate that prions can replicate to high levels in the olfactory sensory epithelium (OSE) in hamsters and that induction of apoptosis in olfactory receptor neurons (ORNs) in the OSE resulted in sloughing off of the OSE from nasal turbinates into the lumen of the nasal airway. In the absence of nasotoxic treatment, olfactory marker protein (OMP), which is specific for ORNs, was not detected in nasal lavage samples. However, after nasotoxic treatment that leads to apoptosis of ORNs, both OMP and prion proteins were present in nasal lavage samples. The cellular debris that was released from the OSE into the lumen of the nasal airway was positive for both OMP and the disease-specific isoform of the prion protein, PrPSc. By using the real-time quaking-induced conversion assay to quantify prions, a 100- to 1,000-fold increase in prion seeding activity was observed in nasal lavage samples following nasotoxic treatment. Since neurons replicate prions to higher levels than other cell types and ORNs are the most environmentally exposed neurons, we propose that an increase in ORN apoptosis or damage to the nasal mucosa in a host with a preexisting prion infection of the OSE could lead to a substantial increase in the release of prion infectivity into nasal samples. This mechanism of prion shedding from the olfactory mucosa could contribute to prion transmission. PMID:22130543

  11. [Development of the Human Olfactory Bulbs in the Prenatal Ontogenesis: an Immunochistochemical Study with Markers of Presynaptic Terminals (anti-SNAP-25, -Synapsin-I, -Synaptophysin)].

    PubMed

    Kharlamova, A S; Barabanov, V M; Saveliev, S V

    2015-01-01

    We provide the data of the olfactory bulbs (OB) development in the human fetuses on the stages from 8 week to birth. Immunochistochemical markers of presynaptic terminals (anti-SNAP-25, -synapsin-I, -synaptophysin) were used to evaluate the maturation of the OB. Differentiation of the OB layers begins from periphery, which implicitly evidences that growth of the olfactory nerves fibers induses not only anatomical differentiation of the OB, but also differentiation of its functional layers. The sites of the developing glomerulus are revealed using the immunochistochemical prosedure on the stage before distinct glomerulus can be identified with common histological procedure. OB conductive system demonstrates immunoreactivity with the antibodies to the presynaptic proteins on the all stages from 10-11 weeks of fetus development. Four stages of the OB development are described. All functional layers of the OB are mature at the 22-weeks stage. Further differentiation of the OB neuroblasts, including lamina formation of the internal granular leyer, glomerular layer development, OB growth continue after 20-22 weeks stage until 38-40 weeks of the fetus develoment. Patterns of the immunoreactivity with antibodies to SNAP-25, synapsin-I and synaptophysin are completely appropriate to those of adult's OB on the 38-40 weeks of the prenatal development. Complete maturity of the human OB is achived at 38-40 weeks of the prenatal development.

  12. Sniff-Like Patterned Input Results in Long-Term Plasticity at the Rat Olfactory Bulb Mitral and Tufted Cell to Granule Cell Synapse

    PubMed Central

    Perez de los Cobos Pallares, Fernando; Loebel, Alex; Lukas, Michael

    2016-01-01

    During odor sensing the activity of principal neurons of the mammalian olfactory bulb, the mitral and tufted cells (MTCs), occurs in repetitive bursts that are synchronized to respiration, reminiscent of hippocampal theta-gamma coupling. Axonless granule cells (GCs) mediate self- and lateral inhibitory interactions between the excitatory MTCs via reciprocal dendrodendritic synapses. We have explored long-term plasticity at this synapse by using a theta burst stimulation (TBS) protocol and variations thereof. GCs were excited via glomerular stimulation in acute brain slices. We find that TBS induces exclusively long-term depression in the majority of experiments, whereas single bursts (“single-sniff paradigm”) can elicit both long-term potentiation and depression. Statistical analysis predicts that the mechanism underlying this bidirectional plasticity involves the proportional addition or removal of presynaptic release sites. Gamma stimulation with the same number of APs as in TBS was less efficient in inducing plasticity. Both TBS- and “single-sniff paradigm”-induced plasticity depend on NMDA receptor activation. Since the onset of plasticity is very rapid and requires little extra activity, we propose that these forms of plasticity might play a role already during an ongoing search for odor sources. Our results imply that components of both short-term and long-term olfactory memory may be encoded at this synapse. PMID:27747107

  13. Robo-2 controls the segregation of a portion of basal vomeronasal sensory neuron axons to the posterior region of the accessory olfactory bulb.

    PubMed

    Prince, Janet E A; Cho, Jin Hyung; Dumontier, Emilie; Andrews, William; Cutforth, Tyler; Tessier-Lavigne, Marc; Parnavelas, John; Cloutier, Jean-François

    2009-11-11

    The ability of sensory systems to detect and process information from the environment relies on the elaboration of precise connections between sensory neurons in the periphery and second order neurons in the CNS. In mice, the accessory olfactory system is thought to regulate a wide variety of social and sexual behaviors. The expression of the Slit receptors Robo-1 and Robo-2 in vomeronasal sensory neurons (VSNs) suggests they may direct the stereotypic targeting of their axons to the accessory olfactory bulb (AOB). Here, we have examined the roles of Robo-1 and Robo-2 in the formation of connections by VSN axons within the AOB. While Robo-1 is not necessary for the segregation of VSN axons within the anterior and posterior regions of the AOB, Robo-2 is required for the targeting of some basal VSN axons to the posterior region of the AOB but is dispensable for the fasciculation of VSN axons. Furthermore, the specific ablation of Robo-2 expression in VSNs leads to mistargeting of a portion of basal VSN axons to the anterior region of the AOB, indicating that Robo-2 expression is required on projecting VSN axons. Together, these results identify Robo-2 as a receptor that controls the targeting of basal VSN axons to the posterior AOB.

  14. Lesion of the Olfactory Epithelium Accelerates Prion Neuroinvasion and Disease Onset when Prion Replication Is Restricted to Neurons

    PubMed Central

    Crowell, Jenna; Wiley, James A.; Bessen, Richard A.

    2015-01-01

    Natural prion diseases of ruminants are moderately contagious and while the gastrointestinal tract is the primary site of prion agent entry, other mucosae may be entry sites in a subset of infections. In the current study we examined prion neuroinvasion and disease induction following disruption of the olfactory epithelium in the nasal mucosa since this site contains environmentally exposed olfactory sensory neurons that project directly into the central nervous system. Here we provide evidence for accelerated prion neuroinvasion and clinical onset from the olfactory mucosa after disruption and regeneration of the olfactory epithelium and when prion replication is restricted to neurons. In transgenic mice with neuron restricted replication of prions, there was a reduction in survival when the olfactory epithelium was disrupted prior to intranasal inoculation and there was >25% decrease in the prion incubation period. In a second model, the neurotropic DY strain of transmissible mink encephalopathy was not pathogenic in hamsters by the nasal route, but 50% of animals exhibited brain infection and/or disease when the olfactory epithelium was disrupted prior to intranasal inoculation. A time course analysis of prion deposition in the brain following loss of the olfactory epithelium in models of neuron-restricted prion replication suggests that neuroinvasion from the olfactory mucosa is via the olfactory nerve or brain stem associated cranial nerves. We propose that induction of neurogenesis after damage to the olfactory epithelium can lead to prion infection of immature olfactory sensory neurons and accelerate prion spread to the brain. PMID:25822718

  15. Microglia and their CX3CR1 signaling are involved in hippocampal- but not olfactory bulb-related memory and neurogenesis.

    PubMed

    Reshef, Ronen; Kreisel, Tirzah; Beroukhim Kay, Dorsa; Yirmiya, Raz

    2014-10-01

    Recent studies demonstrate that microglia play an important role in cognitive and neuroplasticity processes, at least partly via microglial CX3C receptor 1 (CX3CR1) signaling. Furthermore, microglia are responsive to environmental enrichment (EE), which modulates learning, memory and neurogenesis. In the present study we examined the role of microglial CX3CR1 signaling in hippocampal- and olfactory-bulb (OB)-related memory and neurogenesis in homozygous mice with microglia-specific transgenic expression of GFP under the CX3CR1 promoter (CX3CR1(-/-) mice), in which the CX3CR1 gene is functionally deleted, as well as heterozygous CX3CR1(+/-) and WT controls. We report that the CX3CR1-deficient mice displayed better hippocampal-dependent memory functioning and olfactory recognition, along with increased number and soma size of hippocampal microglia, suggestive of mild activation status, but no changes in OB microglia. A similar increase in hippocampal-dependent memory functioning and microglia number was also induced by pharmacological inhibition of CX3CR1 signaling, using chronic (2weeks) i.c.v. administration of CX3CR1 blocking antibody. In control mice, EE improved hippocampal-dependent memory and neurogenesis, and increased hippocampal microglia number and soma size, whereas odor enrichment (OE) improved olfactory recognition and OB neurogenesis without changing OB microglia status. In CX3CR1-deficient mice, EE and OE did not produce any further improvement in memory functioning or neurogenesis and had no effect on microglial status. These results support the notion that in the hippocampus microglia and their interactions with neurons via the CX3CR1 play an important role in memory functioning and neurogenesis, whereas in the OB microglia do not seem to be involved in these processes.

  16. Transient and sustained afterdepolarizations in accessory olfactory bulb mitral cells are mediated by distinct mechanisms that are differentially regulated by neuromodulators

    PubMed Central

    Shpak, Guy; Zylbertal, Asaph; Wagner, Shlomo

    2015-01-01

    Social interactions between mammalian conspecifics rely heavily on molecular communication via the main and accessory olfactory systems. These two chemosensory systems show high similarity in the organization of information flow along their early stages: social chemical cues are detected by the sensory neurons of the main olfactory epithelium and the vomeronasal organ. These neurons then convey sensory information to the main (MOB) and accessory (AOB) olfactory bulbs, respectively, where they synapse upon mitral cells that project to higher brain areas. Yet, the functional difference between these two chemosensory systems remains unclear. We have previously shown that MOB and AOB mitral cells exhibit very distinct intrinsic biophysical properties leading to different types of information processing. Specifically, we found that unlike MOB mitral cells, AOB neurons display persistent firing responses to strong stimuli. These prolonged responses are mediated by long-lasting calcium-activated non-selective cationic current (Ican). In the current study we further examined the firing characteristics of these cells and their modulation by several neuromodulators. We found that AOB mitral cells display transient depolarizing afterpotentials (DAPs) following moderate firing. These DAPs are not found in MOB mitral cells that show instead robust hyperpolarizing afterpotentials. Unlike Ican, the DAPs of AOB mitral cells are activated by low levels of intracellular calcium and are relatively insensitive to flufenamic acid. Moreover, the cholinergic agonist carbachol exerts opposite effects on the persistent firing and DAPs of AOB mitral cells. We conclude that these phenomena are mediated by distinct biophysical mechanisms that may serve to mediate different types of information processing in the AOB at distinct brain states. PMID:25642164

  17. Modulation of Olfactory Bulb Network Activity by Serotonin: Synchronous Inhibition of Mitral Cells Mediated by Spatially Localized GABAergic Microcircuits

    ERIC Educational Resources Information Center

    Schmidt, Loren J.; Strowbridge, Ben W.

    2014-01-01

    Although inhibition has often been proposed as a central mechanism for coordinating activity in the olfactory system, relatively little is known about how activation of different inhibitory local circuit pathways can generate coincident inhibition of principal cells. We used serotonin (5-HT) as a pharmacological tool to induce spiking in ensembles…

  18. A short peptide GPIGS promotes proliferation of hair bulb keratinocytes and accelerates hair regrowth in mice.

    PubMed

    Tsuruda, Akinori; Kawano, Yasuhiro; Maekawa, Takaaki; Oka, Syuichi

    2005-03-01

    The aim of this study was to discover a novel agent that promotes hair growth. We carried out a screening test in 298 types of conditioned medium (CM) from cultures of bacteria by using a hair bulb keratinocyte (HBK) growth assay. As a result, we found a HBK growth factor in the CM of Bacillus sp. M18. This HBK growth factor was purified by collecting biologically active fractions in three steps, including HP-20 batch processing, LH-20 chromatography and C18 reverse-phase high-pressure liquid chromatography, and identified as a short peptide GPIGS. GPIGS increased Akt phosphorylation in HBKs. Moreover, the GPIGS-stimulated HBK growth was inhibited by the treatment with LY294002, an inhibitor of phosphatidylinositol 3-kinase (PI-3K). These results suggest that GPIGS promotes HBK growth via the PI-3K/Akt pathway. In addition to in vitro tests, GPIGS was found to accelerate hair regrowth in telogen mice. Our results indicate that GPIGS is a potential agent to promote hair growth.

  19. Sexual Behavior Increases Cell Proliferation in the Rostral Migratory Stream and Promotes the Differentiation of the New Cells into Neurons in the Accessory Olfactory Bulb of Female Rats

    PubMed Central

    Corona, Rebeca; Retana-Márquez, Socorro; Portillo, Wendy; Paredes, Raúl G.

    2016-01-01

    We have previously demonstrated, that 15 days after female rats pace the sexual interaction, there is an increase in the number of new cells that reach the granular cell layer (GrL) of the accessory olfactory bulb (AOB). The aim of the present study was to evaluate, if the first sexual experience in the female rat increases cell proliferation in the subventricular zone (SVZ) and the rostral migratory stream (RMS). We also tested if this behavior promotes the survival of the new cells that integrate into the main olfactory bulb (MOB) and AOB 45 days after the behavioral test. Sexually, naive female rats were injected with the DNA synthesis marker 5′-bromo-2′-deoxyuridine (BrdU) on the day of the behavioral test. They were randomly divided into the following groups: Female rats placed alone in the mating cage (1); Females exposed to amyl acetate odor [banana scent, (2)]; Females that could see, hear, and smell the male but physical contact was not possible [exposed to male, (3)]; Female rats that could pace the sexual interaction (4); and females that mated without the possibility of pacing the sexual interaction (5). Animals were sacrificed 2 days after the behavioral test (proliferation) or 45 days later (survival). Our results show that 2 days after females were exposed to banana scent or to the male, they had a higher number of cells in the SVZ. Females, that mated in pace and no-paced conditions had more new cells in the RMS. At 45 days, no significant differences were found in the number of new cells that survived in the MOB or in the AOB. However, mating increased the percentage of new cells, that differentiated into neurons in the GrL of the AOB. These new cells expressed c-Fos after a second sexual encounter just before the females were sacrificed. No significant differences in plasma levels of estradiol and progesterone were observed between groups. Our results indicate that the first sexual experience increases cell proliferation in the RMS and mating

  20. Increased doublecortin (DCX) expression and incidence of DCX-immunoreactive multipolar cells in the subventricular zone-olfactory bulb system of suicides

    PubMed Central

    Maheu, Marissa E.; Devorak, Julia; Freibauer, Alexander; Davoli, Maria Antonietta; Turecki, Gustavo; Mechawar, Naguib

    2015-01-01

    Postmortem studies have confirmed the occurrence of adult hippocampal neurogenesis in humans and implicated this process in antidepressant response, yet neurogenesis in other regions remains to be examined in the context of depression. Here we assess the extent of subventricular zone-olfactory bulb (SVZ-OB) neurogenesis in adult humans having died by suicide. Protein expression of proliferative and neurogenic markers Sox2, proliferating cell nuclear antigen, and doublecortin (DCX) were examined in postmortem SVZ and OB samples from depressed suicides and matched sudden-death controls. In the SVZ, DCX-immunoreactive (IR) cells displayed phenotypes typical of progenitors, whereas in the olfactory tract (OT), they were multipolar with variable size and morphologies suggestive of differentiating cells. DCX expression was significantly increased in the OB of suicides, whereas SVZ DCX expression was higher among unmedicated, but not antidepressant-treated, suicides. Although very few DCX-IR cells were present in the control OT, they were considerably more common in suicides and correlated with OB DCX levels. Suicides also displayed higher DCX-IR process volumes. These results support the notion that OB neurogenesis is minimal in adult humans. They further raise the possibility that the differentiation and migration of SVZ-derived neuroblasts may be altered in unmedicated suicides, leading to an accumulation of ectopically differentiating cells in the OT. Normal SVZ DCX expression among suicides receiving antidepressants suggests a potentially novel mode of action of antidepressant medication. Given the modest group sizes and rarity of DCX-IR cells assessed here, a larger-scale characterization will be required before firm conclusions can be made regarding the identity of these cells. PMID:26082689

  1. Optical dissection of odor information processing in vivo using GCaMPs expressed in specified cell types of the olfactory bulb.

    PubMed

    Wachowiak, Matt; Economo, Michael N; Díaz-Quesada, Marta; Brunert, Daniela; Wesson, Daniel W; White, John A; Rothermel, Markus

    2013-03-20

    Understanding central processing requires precise monitoring of neural activity across populations of identified neurons in the intact brain. In the present study, we used recently optimized variants of the genetically encoded calcium sensor GCaMP (GCaMP3 and GCaMPG5G) to image activity among genetically and anatomically defined neuronal populations in the olfactory bulb (OB), including two types of GABAergic interneurons (periglomerular [PG] and short axon [SA] cells) and OB output neurons (mitral/tufted [MT] cells) projecting to the piriform cortex. We first established that changes in neuronal spiking can be related accurately to GCaMP fluorescence changes via a simple quantitative relationship over a large dynamic range. We next used in vivo two-photon imaging from individual neurons and epifluorescence signals reflecting population-level activity to investigate the spatiotemporal representation of odorants across these neuron types in anesthetized and awake mice. Under anesthesia, individual PG and SA cells showed temporally simple responses and little spontaneous activity, whereas MT cells were spontaneously active and showed diverse temporal responses. At the population level, response patterns of PG, SA, and MT cells were surprisingly similar to those imaged from sensory inputs, with shared odorant-specific topography across the dorsal OB and inhalation-coupled temporal dynamics. During wakefulness, PG and SA cell responses increased in magnitude but remained temporally simple, whereas those of MT cells changed to complex spatiotemporal patterns reflecting restricted excitation and widespread inhibition. These results suggest multiple circuit elements with distinct roles in transforming odor representations in the OB and provide a framework for further study of early olfactory processing using optical and genetic tools. PMID:23516293

  2. A comparison between the human sense of smell and neural activity in the olfactory bulb of rats.

    PubMed

    Soh, Zu; Saito, Maki; Kurita, Yuichi; Takiguchi, Noboru; Ohtake, Hisao; Tsuji, Toshio

    2014-02-01

    Generally, odor qualities are evaluated via sensory tests in which predefined criteria are assessed by panelists and stochastically analyzed to reduce human inconsistencies. Because this method requires multiple, well-trained human subjects, a more convenient approach is required to enable predictions of odor qualities. In this article, we propose an approach involving linking internal states of the olfactory system with perceptual characteristics. In the study, the glomerular responses of rats were taken to represent internal olfactory system states. Similarities between the glomerular responses of rats were quantified by correlations between glomerular activity patterns, overlap rate of strongly activated part across glomerular activity patterns, and the similarity between histograms of the strength of activity. These indices were then compared with perceptual similarities measured from human subjects in sensory tests. The results of experiments involving 22 odorants showed medium strength correlations between each index and perceptual similarity. In addition, when the 3 indices were combined using their Euclidean distance, we observed middle to high correlations (r = 0.65-0.79) to human perceptual similarity. We also report the results of our use of a machine learning technique to classify the odorants into a similar and dissimilar category. Although the correct rate of classification varied from 33.3% to 92.9%, these results support the feasibility of linking the glomerular responses of rats to human perception.

  3. Viral-induced encephalitis initiates distinct and functional CD103+ CD11b+ brain dendritic cell populations within the olfactory bulb

    PubMed Central

    D'Agostino, Paul M.; Kwak, Changsoo; Vecchiarelli, Haley A.; Toth, Judit Gal; Miller, James M.; Masheeb, Zahrah; McEwen, Bruce S.; Bulloch, Karen

    2012-01-01

    Dendritic cells (DC) are antigen-presenting cells found in both lymphoid and nonlymphoid organs, including the brain (bDC) of Cd11c/eyfp transgenic C57BL/6 mice. Using an intranasal vesicular stomatitis virus infection, we demonstrated that EYFP+ cells amass in areas associated with viral antigens, take on an activated morphology, and project their processes into infected neuronal tissue within the olfactory bulb. These bDC separated into three EYFP+ CD45+ CD11b+ populations, all but one being able to functionally promote both T lymphocyte proliferation and TH1 cytokine production. One population was shown to emanate from the brain and a second population was peripherally derived. The third population was of indeterminate origin, being both radiosensitive and not replenished by donor bone marrow. Finally, each EYFP+ population contained CD11b+ CD103+ subpopulations and could be distinguished in terms of CD115, Gr-1, and Ly-6C expression, highlighting mucosal and monocyte-derived DC lineages. PMID:22474352

  4. Specification of a Foxj1-dependent lineage in the forebrain is required for embryonic-to-postnatal transition of neurogenesis in the olfactory bulb.

    PubMed

    Jacquet, Benoit V; Muthusamy, Nagendran; Sommerville, Laura J; Xiao, Guanxi; Liang, Huixuan; Zhang, Yong; Holtzman, Michael J; Ghashghaei, H Troy

    2011-06-22

    Establishment of a neural stem cell niche in the postnatal subependymal zone (SEZ) and the rostral migratory stream (RMS) is required for postnatal and adult neurogenesis in the olfactory bulbs (OB). We report the discovery of a cellular lineage in the SEZ-RMS-OB continuum, the specification of which is dependent on the expression of the forkhead transcription factor Foxj1 in mice. Spatially and temporally restricted Foxj1+ neuronal progenitors emerge during embryonic periods, surge during perinatal development, and are active only for the first few postnatal weeks. We show that the development of the unique Foxj1-derived lineage is dependent on Foxj1 expression and is required for overall postnatal neurogenesis in the OB. Strikingly, the production of neurons from Foxj1+ progenitors significantly declines after the early postnatal weeks, but Foxj1-derived neurons in the OB persist during adult periods. For the first time, our study identifies the time- and region-specific activity of a perinatal progenitor domain that is required for transition and progression of OB neurogenesis from the embryonic-to-postnatal periods.

  5. Specification of a Foxj1-dependent lineage in the forebrain is required for embryonic-to-postnatal transition of neurogenesis in the olfactory bulb

    PubMed Central

    Jacquet, Benoit V.; Muthusamy, Nagendran; Sommerville, Laura J.; Xiao, Guanxi; Liang, Huixuan; Zhang, Yong; Holtzman, Michael; Ghashghaei, H. Troy

    2011-01-01

    Establishment of a neural stem cell niche in the postnatal subependymal zone (SEZ) and the rostral migratory stream (RMS) is required for postnatal and adult neurogenesis in the olfactory bulbs (OB). We report the discovery of a cellular lineage in the SEZ-RMS-OB continuum, the specification of which is dependent on the expression of the forkhead transcription factor Foxj1 in mice. Spatially- and temporally- restricted Foxj1+ neuronal progenitors emerge during embryonic periods, surge during perinatal development, and are active only for the first few postnatal weeks. We show that the development of the unique Foxj1-derived lineage is dependent on Foxj1 expression, and is required for overall postnatal neurogenesis in the OB. Strikingly, the production of neurons from Foxj1+ progenitors significantly declines after the early postnatal weeks, but Foxj1-derived neurons in the OB persist during adult periods. Our study for the first time identifies the time-and region-specific activity of a perinatal progenitor domain that is required for transition and progression of OB neurogenesis from the embryonic-to-postnatal periods. PMID:21697387

  6. Polyurethane/polylactide-based biomaterials combined with rat olfactory bulb-derived glial cells and adipose-derived mesenchymal stromal cells for neural regenerative medicine applications.

    PubMed

    Grzesiak, Jakub; Marycz, Krzysztof; Szarek, Dariusz; Bednarz, Paulina; Laska, Jadwiga

    2015-01-01

    Research concerning the elaboration and application of biomaterial which may support the nerve tissue regeneration is currently one of the most promising directions. Biocompatible polymer devices are noteworthy group among the numerous types of potentially attractive biomaterials for regenerative medicine application. Polylactides and polyurethanes may be utilized for developing devices for supporting the nerve regeneration, like nerve guide conduits or bridges connecting the endings of broken nerve tracts. Moreover, the combination of these biomaterial devices with regenerative cell populations, like stem or precursor cells should significantly improve the final therapeutic effect. Therefore, the composition and structure of final device should support the proper adhesion and growth of cells destined for clinical application. In current research, the three polymer mats elaborated for connecting the broken nerve tracts, made from polylactide, polyurethane and their blend were evaluated both for physical properties and in vitro, using the olfactory-bulb glial cells and mesenchymal stem cells. The evaluation of Young's modulus, wettability and roughness of obtained materials showed the differences between analyzed samples. The analysis of cell adhesion, proliferation and morphology showed that the polyurethane-polylactide blend was the most neutral for cells in culture, while in the pure polymer samples there were significant alterations observed. Our results indicated that polyurethane-polylactide blend is an optimal composition for culturing and delivery of glial and mesenchymal stem cells. PMID:25953554

  7. Firing properties of accessory olfactory bulb mitral/tufted cells in response to urine delivered to the vomeronasal organ of gray short-tailed opossums.

    PubMed

    Zhang, Jing-Ji; Huang, Guang-Zhe; Halpern, Mimi

    2007-05-01

    In comparison with many mammals, there is limited knowledge of the role of pheromones in conspecific communication in the gray short-tailed opossum. Here we report that mitral/tufted (M/T) cells of the accessory olfactory bulb (AOB) of male opossums responded to female urine but not to male urine with two distinct patterns: excitation followed by inhibition or inhibition. Either pattern could be mimicked by application of guanosine 5'-O-3-thiotriphosphate and blocked by guanosine 5'-O-2-thiodiphosphate, indicating that the response of neurons in this pathway is through a G-protein-coupled receptor mechanism. In addition, the inhibitor of phospholipase C (PLC), U73122, significantly blocked urine-induced responses. Male and female urine were ineffective as stimuli for M/T cells in the AOB of female opossums. These results indicate that urine of diestrous females contains a pheromone that directly stimulates vomeronasal neurons through activation of PLC by G-protein-coupled receptor mechanisms and that the response to urine is sexually dimorphic.

  8. High-Field MRI Reveals a Drastic Increase of Hypoxia-Induced Microhemorrhages upon Tissue Reoxygenation in the Mouse Brain with Strong Predominance in the Olfactory Bulb

    PubMed Central

    Helluy, Xavier; Milford, David; Heiland, Sabine; Bendszus, Martin

    2016-01-01

    Human pathophysiology of high altitude hypoxic brain injury is not well understood and research on the underlying mechanisms is hampered by the lack of well-characterized animal models. In this study, we explored the evolution of brain injury by magnetic resonance imaging (MRI) and histological methods in mice exposed to normobaric hypoxia at 8% oxygen for 48 hours followed by rapid reoxygenation and incubation for further 24 h under normoxic conditions. T2*-, diffusion-weighted and T2-relaxometry MRI was performed before exposure, immediately after 48 hours of hypoxia and 24 hours after reoxygenation. Cerebral microhemorrhages, previously described in humans suffering from severe high altitude cerebral edema, were also detected in mice upon hypoxia-reoxygenation with a strong region-specific clustering in the olfactory bulb, and to a lesser extent, in the basal ganglia and cerebral white matter. The number of microhemorrhages determined immediately after hypoxia was low, but strongly increased 24 hours upon onset of reoxygenation. Histologically verified microhemorrhages were exclusively located around cerebral microvessels with disrupted interendothelial tight junction protein ZO-1. In contrast, quantitative T2 and apparent-diffusion-coefficient values immediately after hypoxia and after 24 hours of reoxygenation did not show any region-specific alteration, consistent with subtle multifocal but not with regional or global brain edema. PMID:26863147

  9. Polyurethane/polylactide-based biomaterials combined with rat olfactory bulb-derived glial cells and adipose-derived mesenchymal stromal cells for neural regenerative medicine applications.

    PubMed

    Grzesiak, Jakub; Marycz, Krzysztof; Szarek, Dariusz; Bednarz, Paulina; Laska, Jadwiga

    2015-01-01

    Research concerning the elaboration and application of biomaterial which may support the nerve tissue regeneration is currently one of the most promising directions. Biocompatible polymer devices are noteworthy group among the numerous types of potentially attractive biomaterials for regenerative medicine application. Polylactides and polyurethanes may be utilized for developing devices for supporting the nerve regeneration, like nerve guide conduits or bridges connecting the endings of broken nerve tracts. Moreover, the combination of these biomaterial devices with regenerative cell populations, like stem or precursor cells should significantly improve the final therapeutic effect. Therefore, the composition and structure of final device should support the proper adhesion and growth of cells destined for clinical application. In current research, the three polymer mats elaborated for connecting the broken nerve tracts, made from polylactide, polyurethane and their blend were evaluated both for physical properties and in vitro, using the olfactory-bulb glial cells and mesenchymal stem cells. The evaluation of Young's modulus, wettability and roughness of obtained materials showed the differences between analyzed samples. The analysis of cell adhesion, proliferation and morphology showed that the polyurethane-polylactide blend was the most neutral for cells in culture, while in the pure polymer samples there were significant alterations observed. Our results indicated that polyurethane-polylactide blend is an optimal composition for culturing and delivery of glial and mesenchymal stem cells.

  10. High-Field MRI Reveals a Drastic Increase of Hypoxia-Induced Microhemorrhages upon Tissue Reoxygenation in the Mouse Brain with Strong Predominance in the Olfactory Bulb.

    PubMed

    Hoffmann, Angelika; Kunze, Reiner; Helluy, Xavier; Milford, David; Heiland, Sabine; Bendszus, Martin; Pham, Mirko; Marti, Hugo H

    2016-01-01

    Human pathophysiology of high altitude hypoxic brain injury is not well understood and research on the underlying mechanisms is hampered by the lack of well-characterized animal models. In this study, we explored the evolution of brain injury by magnetic resonance imaging (MRI) and histological methods in mice exposed to normobaric hypoxia at 8% oxygen for 48 hours followed by rapid reoxygenation and incubation for further 24 h under normoxic conditions. T2*-, diffusion-weighted and T2-relaxometry MRI was performed before exposure, immediately after 48 hours of hypoxia and 24 hours after reoxygenation. Cerebral microhemorrhages, previously described in humans suffering from severe high altitude cerebral edema, were also detected in mice upon hypoxia-reoxygenation with a strong region-specific clustering in the olfactory bulb, and to a lesser extent, in the basal ganglia and cerebral white matter. The number of microhemorrhages determined immediately after hypoxia was low, but strongly increased 24 hours upon onset of reoxygenation. Histologically verified microhemorrhages were exclusively located around cerebral microvessels with disrupted interendothelial tight junction protein ZO-1. In contrast, quantitative T2 and apparent-diffusion-coefficient values immediately after hypoxia and after 24 hours of reoxygenation did not show any region-specific alteration, consistent with subtle multifocal but not with regional or global brain edema. PMID:26863147

  11. Neurogenesis, Neurodegeneration, Interneuron Vulnerability, and Amyloid-β in the Olfactory Bulb of APP/PS1 Mouse Model of Alzheimer's Disease

    PubMed Central

    De la Rosa-Prieto, Carlos; Saiz-Sanchez, Daniel; Ubeda-Banon, Isabel; Flores-Cuadrado, Alicia; Martinez-Marcos, Alino

    2016-01-01

    Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, mostly idiopathic and with palliative treatment. Neuropathologically, it is characterized by intracellular neurofibrillary tangles of tau protein and extracellular plaques of amyloid β peptides. The relationship between AD and neurogenesis is unknown, but two facts are particularly relevant. First, early aggregation sites of both proteinopathies include the hippocampal formation and the olfactory bulb (OB), which have been correlated to memory and olfactory deficits, respectively. These areas are well-recognized integration zones of newly-born neurons in the adult brain. Second, molecules, such as amyloid precursor protein (APP) and presenilin-1 are common to both AD etiology and neurogenic development. Adult neurogenesis in AD models has been studied in the hippocampus, but only occasionally addressed in the OB and results are contradictory. To gain insight on the relationship between adult neurogenesis and AD, this work analyzes neurogenesis, neurodegeneration, interneuron vulnerability, and amyloid-β involvement in the OB of an AD model. Control and double-transgenic mice carrying the APP and the presenilin-1 genes, which give rise amyloid β plaques have been used. BrdU-treated animals have been studied at 16, 30, 43, and 56 weeks of age. New-born cell survival (BrdU), neuronal loss (using neuronal markers NeuN and PGP9.5), differential interneuron (calbindin-, parvalbumin-, calretinin- and somatostatin-expressing populations) vulnerability, and involvement by amyloid β have been analyzed. Neurogenesis increases with aging in the granule cell layer of control animals from 16 to 43 weeks. No neuronal loss has been observed after quantifying NeuN or PGP9.5. Regarding interneuron population vulnerability: calbindin-expressing neurons remains unchanged; parvalbumin-expressing neurons trend to increase with aging in transgenic animals; calretinin-expressing neurons increase with aging in

  12. Competing Mechanisms of Gamma and Beta Oscillations in the Olfactory Bulb Based on Multimodal Inhibition of Mitral Cells Over a Respiratory Cycle123

    PubMed Central

    Courtiol, Emmanuelle; Buonviso, Nathalie

    2015-01-01

    Gamma (∼40-90 Hz) and beta (∼15-40 Hz) oscillations and their associated neuronal assemblies are key features of neuronal sensory processing. However, the mechanisms involved in either their interaction and/or the switch between these different regimes in most sensory systems remain misunderstood. Based on in vivo recordings and biophysical modeling of the mammalian olfactory bulb (OB), we propose a general scheme where OB internal dynamics can sustain two distinct dynamic states, each dominated by either a gamma or a beta regime. The occurrence of each regime depends on the excitability level of granule cells, the main OB interneurons. Using this model framework, we demonstrate how the balance between sensory and centrifugal input can control the switch between the two oscillatory dynamic states. In parallel, we experimentally observed that sensory and centrifugal inputs to the rat OB could both be modulated by the respiration of the animal (2-12 Hz) and each one phase shifted with the other. Implementing this phase shift in our model resulted in the appearance of the alternation between gamma and beta rhythms within a single respiratory cycle, as in our experimental results under urethane anesthesia. Our theoretical framework can also account for the oscillatory frequency response, depending on the odor intensity, the odor valence, and the animal sniffing strategy observed under various conditions including animal freely-moving. Importantly, the results of the present model can form a basis to understand how fast rhythms could be controlled by the slower sensory and centrifugal modulations linked to the respiration. Visual Abstract: See Abstract PMID:26665163

  13. Prolactin administration during early postnatal life decreases hippocampal and olfactory bulb neurogenesis and results in depressive-like behavior in adulthood.

    PubMed

    Lajud, Naima; Gonzalez-Zapien, Rubén; Roque, Angélica; Tinajero, Eréndira; Valdez, Juan José; Clapp, Carmen; Torner, Luz

    2013-11-01

    Tight regulation of hormone and neurochemical milieu during developmental periods is critical for adequate physiological functions. For instance, activation of peptide systems during early life stress induces morphological changes in the brain resulting in depression and anxiety disorders. Prolactin (PRL) exerts different actions within the brain; it regulates neurogenesis and modulates neuroendocrine functions in the adult. However, PRL effects during early postnatal life are hardly known. Therefore, we examined whether neonatal administration of PRL influences cell survival in the hippocampal dentate gyrus (DG) and in the olfactory bulb (OB) and whether such influence results in behavioral consequences in adulthood. PRL-treated rat pups (13 mg/kg; PND1 to PND14), injected with BrdU at postnatal day 5 (PND5), showed a decrease in the density of DG BrdU/DCX and BrdU/NeuN-positive cells that survive at PND15. Similarly, PRL treatment decreased the density of BrdU+ cells in the OB compared with VEH. Fluorojade B analysis showed no significant changes in the amount of cell death in the DG between the groups. Postnatal PRL administration induced a passive coping strategy in the forced swimming test in male and female adult rats when compared with control and vehicle groups. Corticosterone endogenous levels at PND12 were not affected by PRL or VEH treatment. Altogether, these results suggest that opposed to its effects in the adult, postnatal PRL treatment affects neurogenesis and results in psychopathology later in life. High PRL levels, as observed in neonates under several pathological states, might contribute to detrimental effects on the developing brain.

  14. Circadian PER2::LUC rhythms in the olfactory bulb of freely moving mice depend on the suprachiasmatic nucleus but not on behaviour rhythms.

    PubMed

    Ono, Daisuke; Honma, Sato; Honma, Ken-Ichi

    2015-12-01

    The temporal order of physiology and behaviour in mammals is regulated by the coordination of the master circadian clock in the suprachiasmatic nucleus (SCN) and peripheral clocks in various tissues outside the SCN. Because the circadian oscillator(s) in the olfactory bulb (OB) is regarded as SCN independent, we examined the relationship between the SCN master clock and the circadian clock in the OB. We also examined the role of vasoactive intestinal peptide receptor 2 in the circadian organization of the OB. We continuously monitored the circadian rhythms of a clock gene product PER2 in the SCN and OB of freely moving mice by means of a bioluminescence reporter and an optical fibre implanted in the brain. Robust circadian rhythms were detected in the OB and SCN for up to 19 days. Bilateral SCN lesions abolished the circadian behaviour rhythms and disorganized the PER2 rhythms in the OB. The PER2 rhythms in the OB showed more than one oscillatory component of a similar circadian period, suggesting internal desynchronization of constituent oscillators. By contrast, significant circadian PER2 rhythms were detected in the vasoactive intestinal peptide receptor 2-deficient mice, despite the substantial deterioration or abolition of circadian behavioural rhythms. These findings indicate that the circadian clock in the OB of freely moving mice depends on the SCN master clock but not on the circadian behavioural rhythms. The circadian PER2::LUC rhythm in the cultured OB was as robust as that in the cultured SCN but reset by slice preparation, suggesting that culturing of the slice reinforces the circadian rhythm.

  15. Pax6 Is Essential for the Maintenance and Multi-Lineage Differentiation of Neural Stem Cells, and for Neuronal Incorporation into the Adult Olfactory Bulb

    PubMed Central

    Curto, Gloria G.; Nieto-Estévez, Vanesa; Hurtado-Chong, Anahí; Valero, Jorge; Gómez, Carmela; Alonso, José R.; Weruaga, Eduardo

    2014-01-01

    The paired type homeobox 6 (Pax6) transcription factor (TF) regulates multiple aspects of neural stem cell (NSC) and neuron development in the embryonic central nervous system. However, less is known about the role of Pax6 in the maintenance and differentiation of adult NSCs and in adult neurogenesis. Using the +/SeyDey mouse, we have analyzed how Pax6 heterozygosis influences the self-renewal and proliferation of adult olfactory bulb stem cells (aOBSCs). In addition, we assessed its influence on neural differentiation, neuronal incorporation, and cell death in the adult OB, both in vivo and in vitro. Our results indicate that the Pax6 mutation alters Nestin+-cell proliferation in vivo, as well as self-renewal, proliferation, and survival of aOBSCs in vitro although a subpopulation of +/SeyDey progenitors is able to expand partially similar to wild-type progenitors. This mutation also impairs aOBSC differentiation into neurons and oligodendrocytes, whereas it increases cell death while preserving astrocyte survival and differentiation. Furthermore, Pax6 heterozygosis causes a reduction in the variety of neurochemical interneuron subtypes generated from aOBSCs in vitro and in the incorporation of newly generated neurons into the OB in vivo. Our findings support an important role of Pax6 in the maintenance of aOBSCs by regulating cell death, self-renewal, and cell fate, as well as in neuronal incorporation into the adult OB. They also suggest that deregulation of the cell cycle machinery and TF expression in aOBSCs which are deficient in Pax6 may be at the origin of the phenotypes observed in this adult NSC population. PMID:25117830

  16. Targeted Deletion of ERK5 MAP Kinase in the Developing Nervous System Impairs Development of GABAergic Interneurons in the Main Olfactory Bulb and Behavioral Discrimination between Structurally Similar Odorants

    PubMed Central

    Zou, Junhui; Pan, Yung-Wei; Wang, Zhenshan; Chang, Shih-Yu; Wang, Wenbin; Wang, Xin; Tournier, Cathy; Storm, Daniel R.; Xia, Zhengui

    2012-01-01

    ERK5 MAP kinase is highly expressed in the developing nervous system and has been implicated in promoting the survival of immature neurons in culture. However, its role in the development and function of the mammalian nervous system has not been established in vivo. Here, we report that conditional deletion of the erk5 gene in mouse neural stem cells during development reduces the number of GABAergic interneurons in the main olfactory bulb (OB). Our data suggest that this is due to a decrease in proliferation and an increase in apoptosis in the subventricular zone (SVZ) and rostral migratory stream (RMS) of ERK5 mutant mice. Interestingly, ERK5 mutant mice have smaller OB and are impaired in odor discrimination between structurally similar odorants. We conclude that ERK5 is a novel signaling pathway regulating developmental OB neurogenesis and olfactory behavior. PMID:22442076

  17. Below-ground plant parts emit herbivore-induced volatiles: olfactory responses of a predatory mite to tulip bulbs infested by rust mites.

    PubMed

    Aratchige, N S; Lesna, I; Sabelis, M W

    2004-01-01

    Although odour-mediated interactions among plants, spider mites and predatory mites have been extensively studied above-ground, belowground studies are in their infancy. In this paper, we investigate whether feeding by rust mites (Aceria tulipae) cause tulip bulbs to produce odours that attract predatory mites (Neoseiulus cucumeris). Since our aim was to demonstrate such odours and not their relevance under soil conditions, the experiments were carried out using a classic Y-tube olfactometer in which the predators moved on a Y-shaped wire in open air. We found that food-deprived female predators can discriminate between odours from infested bulbs and odours from uninfested bulbs or artificially wounded bulbs. No significant difference in attractiveness to predators was found between clean bulbs and bulbs either wounded 30 min or 3 h before the experiment. These results indicate that it may not be simply the wounding of the bulbs, but rather the feeding by rust mites, which causes the bulb to release odours that attract N. cucumeris. Since bulbs are belowground plant structures, the olfactometer results demonstrate the potential for odour-mediated interactions in the soil. However, their importance in the actual soil medium remains to be demonstrated.

  18. Acetylcholine and Olfactory Perceptual Learning

    ERIC Educational Resources Information Center

    Wilson, Donald A.; Fletcher, Max L.; Sullivan, Regina M.

    2004-01-01

    Olfactory perceptual learning is a relatively long-term, learned increase in perceptual acuity, and has been described in both humans and animals. Data from recent electrophysiological studies have indicated that olfactory perceptual learning may be correlated with changes in odorant receptive fields of neurons in the olfactory bulb and piriform…

  19. Olfactory system and demyelination.

    PubMed

    Garcia-Gonzalez, D; Murcia-Belmonte, V; Clemente, D; De Castro, F

    2013-09-01

    Within the central nervous system, the olfactory system represents one of the most exciting scenarios since it presents relevant examples of long-life sustained neurogenesis and continuous axonal outgrowth from the olfactory epithelium with the subsequent plasticity phenomena in the olfactory bulb. The olfactory nerve is composed of nonmyelinated axons with interesting ontogenetic interpretations. However, the centripetal projections from the olfactory bulb are myelinated axons which project to more caudal areas along the lateral olfactory tract. In consequence, demyelination has not been considered as a possible cause of the olfactory symptoms in those diseases in which this sense is impaired. One prototypical example of an olfactory disease is Kallmann syndrome, in which different mutations give rise to combined anosmia and hypogonadotropic hypogonadism, together with different satellite symptoms. Anosmin-1 is the extracellular matrix glycoprotein altered in the X-linked form of this disease, which participates in cell adhesion and migration, and axonal outgrowth in the olfactory system and in other regions of the central nervous system. Recently, we have described a new patho-physiological role of this protein in the absence of spontaneous remyelination in multiple sclerosis. In the present review, we hypothesize about how both main and satellite neurological symptoms of Kallmann syndrome may be explained by alterations in the myelination. We revisit the relationship between the olfactory system and myelin highlighting that minor histological changes should not be forgotten as putative causes of olfactory malfunction.

  20. Effects of Human Alpha-Synuclein A53T-A30P Mutations on SVZ and Local Olfactory Bulb Cell Proliferation in a Transgenic Rat Model of Parkinson Disease

    PubMed Central

    Lelan, Faustine; Boyer, Cécile; Thinard, Reynald; Rémy, Séverine; Usal, Claire; Tesson, Laurent; Anegon, Ignacio; Neveu, Isabelle; Damier, Philippe; Naveilhan, Philippe; Lescaudron, Laurent

    2011-01-01

    A transgenic Sprague Dawley rat bearing the A30P and A53T α-synuclein (α-syn) human mutations under the control of the tyrosine hydroxylase promoter was generated in order to get a better understanding of the role of the human α-syn mutations on the neuropathological events involved in the progression of the Parkinson's disease (PD). This rat displayed olfactory deficits in the absence of motor impairments as observed in most early PD cases. In order to investigate the role of the mutated α-syn on cell proliferation, we focused on the subventricular zone (SVZ) and the olfactory bulbs (OB) as a change of the proliferation could affect OB function. The effect on OB dopaminergic innervation was investigated. The human α-syn co-localized in TH-positive OB neurons. No human α-syn was visualized in the SVZ. A significant increase in resident cell proliferation in the glomerular but not in the granular layers of the OB and in the SVZ was observed. TH innervation was significantly increased within the glomerular layer without an increase in the size of the glomeruli. Our rat could be a good model to investigate the role of human mutated α-syn on the development of olfactory deficits. PMID:21766003

  1. Bulb Miser

    NASA Technical Reports Server (NTRS)

    1978-01-01

    The Bulb-Miser was developed during NASA's Apollo program to protect the Saturn launch vehicle from electrical current surge. It is now being produced for the commercial market by Bulb-Miser, Inc., Houston, Texas. Technically known as a "temperature compensating thermistor," the Bulb-Miser is a simple, inexpensive device which looks like a washer about the size of a quarter. It is slipped between bulb and socket and can be used with any incandescent bulb that screws into a standard socket. In addition to delaying burnout, the Bulb-Miser also offers some reduction of electrical energy. But the economy of the device goes beyond energy use or bulb cost; to big users of bulbs, it makes possible substantially lower maintenance labor costs. One field test involving an apartment complex showed that it took two men 30 man hours monthly to replace light bulbs; after Bulb-Miser installation only nine man hours a month were needed. Bulb-Misers are used not only in private homes but also by hospitals, schools, hotels and motels, restaurants, banks and firms providing contract maintenance for large outdoor electric signs. The broadest use is in industrial facilities; the list of big companies which have purchased the Bulb-Miser reads like a Who's Who of American industry.

  2. Olfactory system oscillations across phyla

    PubMed Central

    Kay, Leslie M.

    2014-01-01

    Neural oscillations are ubiquitous in olfactory systems of mammals, insects and molluscs. Neurophysiological and computational investigations point to common mechanisms for gamma or odor associated oscillations across phyla (40–100 Hz in mammals, 20–30 Hz in insects, 0.5–1.5 Hz in molluscs), engaging the reciprocal dendrodendritic synapse between excitatory principle neurons and inhibitory interneurons in the olfactory bulb, antennal lobe, or procerebrum. Recent studies suggest important mechanisms that may modulate gamma oscillations, including neuromodulators and centrifugal input to the olfactory bulb and antennal lobe. Beta (20 Hz) and theta (2–12 Hz) oscillations coordinate activity within and across brain regions. Olfactory beta oscillations are associated with odor learning and depend on centrifugal olfactory bulb input, while theta oscillations are strongly associated with respiration. PMID:25460070

  3. Accelerated age-related olfactory decline among type 1 Usher patients

    PubMed Central

    Ribeiro, João Carlos; Oliveiros, Bárbara; Pereira, Paulo; António, Natália; Hummel, Thomas; Paiva, António; Silva, Eduardo D.

    2016-01-01

    Usher Syndrome (USH) is a rare disease with hearing loss, retinitis pigmentosa and, sometimes, vestibular dysfunction. A phenotype heterogeneity is reported. Recent evidence indicates that USH is likely to belong to an emerging class of sensory ciliopathies. Olfaction has recently been implicated in ciliopathies, but the scarce literature about olfaction in USH show conflicting results. We aim to evaluate olfactory impairment as a possible clinical manifestation of USH. Prospective clinical study that included 65 patients with USH and 65 normal age-gender-smoking-habits pair matched subjects. A cross culturally validated version of the Sniffin’ Sticks olfaction test was used. Young patients with USH have significantly better olfactory scores than healthy controls. We observe that USH type 1 have a faster ageing olfactory decrease than what happens in healthy subjects, leading to significantly lower olfactory scores in older USH1 patients. Moreover, USH type 1 patients showed significantly higher olfactory scores than USH type 2, what can help distinguishing them. Olfaction represents an attractive tool for USH type classification and pre diagnostic screening due to the low cost and non-invasive nature of the testing. Olfactory dysfunction should be considered among the spectrum of clinical manifestations of Usher syndrome. PMID:27329700

  4. The Beneficial Impact of Antidepressant Drugs on Prenatal Stress-Evoked Malfunction of the Insulin-Like Growth Factor-1 (IGF-1) Protein Family in the Olfactory Bulbs of Adult Rats.

    PubMed

    Trojan, Ewa; Głombik, Katarzyna; Ślusarczyk, Joanna; Budziszewska, Bogusława; Kubera, Marta; Roman, Adam; Lasoń, Władysław; Basta-Kaim, Agnieszka

    2016-02-01

    Insulin-like growth factor-1 (IGF-1) promotes the growth, differentiation, and survival of both neurons and glial cells, and it is believed to exert antidepressant-like activity. Thus, disturbances in the IGF-1 system could be responsible for the course of depression. To date, there have been no papers showing the impact of chronic antidepressant treatment on the IGF-1 network in the olfactory bulb (OB) in an animal model of depression. Prenatal stress was used as model of depression. Twenty-four 3-month-old male offspring of control and stressed mothers were subjected to behavioral testing (forced swim test). The mRNA expression of IGF-1 and IGF-1 receptor (IGF-1R) and the protein level of IGF-1 and its phosphorylation, as well as the concentrations of IGF-binding proteins (IGFBP-2, -4, -3, and -6), were measured in OBs before and after chronic imipramine, fluoxetine, or tianeptine administration. Adult rats exposed prenatally to stressful stimuli displayed not only depression-like behavior but also decreased IGF-1 expression, dysregulation in the IGFBP network, and diminished mRNA expression, as well as IGF-1R phosphorylation, in the OB. The administration of antidepressants normalized most of the changes in the IGF-1 system of the OB evoked by prenatal stress. These results suggested a beneficial effect of chronic antidepressant drug treatment in the alleviation of IGF-1 family malfunction in OBs in an animal model of depression.

  5. The Beneficial Impact of Antidepressant Drugs on Prenatal Stress-Evoked Malfunction of the Insulin-Like Growth Factor-1 (IGF-1) Protein Family in the Olfactory Bulbs of Adult Rats.

    PubMed

    Trojan, Ewa; Głombik, Katarzyna; Ślusarczyk, Joanna; Budziszewska, Bogusława; Kubera, Marta; Roman, Adam; Lasoń, Władysław; Basta-Kaim, Agnieszka

    2016-02-01

    Insulin-like growth factor-1 (IGF-1) promotes the growth, differentiation, and survival of both neurons and glial cells, and it is believed to exert antidepressant-like activity. Thus, disturbances in the IGF-1 system could be responsible for the course of depression. To date, there have been no papers showing the impact of chronic antidepressant treatment on the IGF-1 network in the olfactory bulb (OB) in an animal model of depression. Prenatal stress was used as model of depression. Twenty-four 3-month-old male offspring of control and stressed mothers were subjected to behavioral testing (forced swim test). The mRNA expression of IGF-1 and IGF-1 receptor (IGF-1R) and the protein level of IGF-1 and its phosphorylation, as well as the concentrations of IGF-binding proteins (IGFBP-2, -4, -3, and -6), were measured in OBs before and after chronic imipramine, fluoxetine, or tianeptine administration. Adult rats exposed prenatally to stressful stimuli displayed not only depression-like behavior but also decreased IGF-1 expression, dysregulation in the IGFBP network, and diminished mRNA expression, as well as IGF-1R phosphorylation, in the OB. The administration of antidepressants normalized most of the changes in the IGF-1 system of the OB evoked by prenatal stress. These results suggested a beneficial effect of chronic antidepressant drug treatment in the alleviation of IGF-1 family malfunction in OBs in an animal model of depression. PMID:26610812

  6. In silico analysis of gene expression profiles in the olfactory mucosae of aging senescence-accelerated mice.

    PubMed

    Getchell, Thomas V; Peng, Xuejun; Green, C Paul; Stromberg, Arnold J; Chen, Kuey-Chu; Mattson, Mark P; Getchell, Marilyn L

    2004-08-01

    We utilized high-density Affymetrix oligonucleotide arrays to investigate gene expression in the olfactory mucosae of near age-matched aging senescence-accelerated mice (SAM). The senescence-prone (SAMP) strain has a significantly shorter lifespan than does the senescence-resistant (SAMR) strain. To analyze our data, we applied biostatistical methods that included a correlation analysis to evaluate sources of methodologic and biological variability; a two-sided t-test to identify a subpopulation of Present genes with a biologically relevant P-value <0.05; and a false discovery rate (FDR) analysis adjusted to a stringent 5% level that yielded 127 genes with a P-value of <0.001 that were differentially regulated in near age-matched SAMPs (SAMP-Os; 13.75 months) compared to SAMRs (SAMR-Os, 12.5 months). Volcano plots related the variability in the mean hybridization signals as determined by the two-sided t-test to fold changes in gene expression. The genes were categorized into the six functional groups used previously in gene profiling experiments to identify candidate genes that may be relevant for senescence at the genomic and cellular levels in the aging mouse brain (Lee et al. [2000] Nat Genet 25:294-297) and in the olfactory mucosa (Getchell et al. [2003] Ageing Res Rev 2:211-243), which serves several functions that include chemosensory detection, immune barrier function, xenobiotic metabolism, and neurogenesis. Because SAMR-Os and SAMP-Os have substantially different median lifespans, we related the rate constant alpha in the Gompertz equation on aging to intrinsic as opposed to environmental mechanisms of senescence based on our analysis of genes modulated during aging in the olfactory mucosa. PMID:15248299

  7. Multimodal imaging of subventricular zone neural stem/progenitor cells in the cuprizone mouse model reveals increased neurogenic potential for the olfactory bulb pathway, but no contribution to remyelination of the corpus callosum.

    PubMed

    Guglielmetti, Caroline; Praet, Jelle; Rangarajan, Janaki Raman; Vreys, Ruth; De Vocht, Nathalie; Maes, Frederik; Verhoye, Marleen; Ponsaerts, Peter; Van der Linden, Annemie

    2014-02-01

    Multiple sclerosis is a devastating demyelinating disease of the central nervous system (CNS) in which endogenous remyelination, and thus recovery, often fails. Although the cuprizone mouse model allowed elucidation of many molecular factors governing remyelination, currently very little is known about the spatial origin of the oligodendrocyte progenitor cells that initiate remyelination in this model. Therefore, we here investigated in this model whether subventricular zone (SVZ) neural stem/progenitor cells (NSPCs) contribute to remyelination of the splenium following cuprizone-induced demyelination. Experimentally, from the day of in situ NSPC labeling, C57BL/6J mice were fed a 0.2% cuprizone diet during a 4-week period and then left to recover on a normal diet for 8weeks. Two in situ labeling strategies were employed: (i) NSPCs were labeled by intraventricular injection of micron-sized iron oxide particles and then followed up longitudinally by means of magnetic resonance imaging (MRI), and (ii) SVZ NSPCs were transduced with a lentiviral vector encoding the eGFP and Luciferase reporter proteins for longitudinal monitoring by means of in vivo bioluminescence imaging (BLI). In contrast to preceding suggestions, no migration of SVZ NSPC towards the demyelinated splenium was observed using both MRI and BLI, and further validated by histological analysis, thereby demonstrating that SVZ NSPCs are unable to contribute directly to remyelination of the splenium in the cuprizone model. Interestingly, using longitudinal BLI analysis and confirmed by histological analysis, an increased migration of SVZ NSPC-derived neuroblasts towards the olfactory bulb was observed following cuprizone treatment, indicative for a potential link between CNS inflammation and increased neurogenesis.

  8. Neural Correlates of Olfactory Learning: Critical Role of Centrifugal Neuromodulation

    ERIC Educational Resources Information Center

    Fletcher, Max L.; Chen, Wei R.

    2010-01-01

    The mammalian olfactory system is well established for its remarkable capability of undergoing experience-dependent plasticity. Although this process involves changes at multiple stages throughout the central olfactory pathway, even the early stages of processing, such as the olfactory bulb and piriform cortex, can display a high degree of…

  9. Preliminary Modeling and Simulation Study on Olfactory Cell Sensation

    SciTech Connect

    Zhou Jun; Chen Peihua; Liu Qingjun; Wang Ping; Yang Wei

    2009-05-23

    This paper introduced olfactory sensory neuron's whole-cell model with a concrete voltage-gated ionic channels and simulation. Though there are many models in olfactory sensory neuron and olfactory bulb, it remains uncertain how they express the logic of olfactory information processing. In this article, the olfactory neural network model is also introduced. This model specifies the connections among neural ensembles of the olfactory system. The simulation results of the neural network model are consistent with the observed olfactory biological characteristics such as 1/f-type power spectrum and oscillations.

  10. Preliminary Modeling and Simulation Study on Olfactory Cell Sensation

    NASA Astrophysics Data System (ADS)

    Zhou, Jun; Yang, Wei; Chen, Peihua; Liu, Qingjun; Wang, Ping

    2009-05-01

    This paper introduced olfactory sensory neuron's whole-cell model with a concrete voltage-gated ionic channels and simulation. Though there are many models in olfactory sensory neuron and olfactory bulb, it remains uncertain how they express the logic of olfactory information processing. In this article, the olfactory neural network model is also introduced. This model specifies the connections among neural ensembles of the olfactory system. The simulation results of the neural network model are consistent with the observed olfactory biological characteristics such as 1/f-type power spectrum and oscillations.

  11. Anatomical specializations for enhanced olfactory sensitivity in kiwi, Apteryx mantelli.

    PubMed

    Corfield, Jeremy R; Eisthen, Heather L; Iwaniuk, Andrew N; Parsons, Stuart

    2014-01-01

    The ability to function in a nocturnal and ground-dwelling niche requires a unique set of sensory specializations. The New Zealand kiwi has shifted away from vision, instead relying on auditory and tactile stimuli to function in its environment and locate prey. Behavioral evidence suggests that kiwi also rely on their sense of smell, using olfactory cues in foraging and possibly also in communication and social interactions. Anatomical studies appear to support these observations: the olfactory bulbs and tubercles have been suggested to be large in the kiwi relative to other birds, although the extent of this enlargement is poorly understood. In this study, we examine the size of the olfactory bulbs in kiwi and compare them with 55 other bird species, including emus, ostriches, rheas, tinamous, and 2 extinct species of moa (Dinornithiformes). We also examine the cytoarchitecture of the olfactory bulbs and olfactory epithelium to determine if any neural specializations beyond size are present that would increase olfactory acuity. Kiwi were a clear outlier in our analysis, with olfactory bulbs that are proportionately larger than those of any other bird in this study. Emus, close relatives of the kiwi, also had a relative enlargement of the olfactory bulbs, possibly supporting a phylogenetic link to well-developed olfaction. The olfactory bulbs in kiwi are almost in direct contact with the olfactory epithelium, which is indeed well developed and complex, with olfactory receptor cells occupying a large percentage of the epithelium. The anatomy of the kiwi olfactory system supports an enhancement for olfactory sensitivities, which is undoubtedly associated with their unique nocturnal niche. PMID:25376305

  12. Anatomical specializations for enhanced olfactory sensitivity in kiwi, Apteryx mantelli.

    PubMed

    Corfield, Jeremy R; Eisthen, Heather L; Iwaniuk, Andrew N; Parsons, Stuart

    2014-01-01

    The ability to function in a nocturnal and ground-dwelling niche requires a unique set of sensory specializations. The New Zealand kiwi has shifted away from vision, instead relying on auditory and tactile stimuli to function in its environment and locate prey. Behavioral evidence suggests that kiwi also rely on their sense of smell, using olfactory cues in foraging and possibly also in communication and social interactions. Anatomical studies appear to support these observations: the olfactory bulbs and tubercles have been suggested to be large in the kiwi relative to other birds, although the extent of this enlargement is poorly understood. In this study, we examine the size of the olfactory bulbs in kiwi and compare them with 55 other bird species, including emus, ostriches, rheas, tinamous, and 2 extinct species of moa (Dinornithiformes). We also examine the cytoarchitecture of the olfactory bulbs and olfactory epithelium to determine if any neural specializations beyond size are present that would increase olfactory acuity. Kiwi were a clear outlier in our analysis, with olfactory bulbs that are proportionately larger than those of any other bird in this study. Emus, close relatives of the kiwi, also had a relative enlargement of the olfactory bulbs, possibly supporting a phylogenetic link to well-developed olfaction. The olfactory bulbs in kiwi are almost in direct contact with the olfactory epithelium, which is indeed well developed and complex, with olfactory receptor cells occupying a large percentage of the epithelium. The anatomy of the kiwi olfactory system supports an enhancement for olfactory sensitivities, which is undoubtedly associated with their unique nocturnal niche.

  13. Olfactory Fear Conditioning Induces Field Potential Potentiation in Rat Olfactory Cortex and Amygdala

    ERIC Educational Resources Information Center

    Messaoudi, Belkacem; Granjon, Lionel; Mouly, Anne-Marie; Sevelinges, Yannick; Gervais, Remi

    2004-01-01

    The widely used Pavlovian fear-conditioning paradigms used for studying the neurobiology of learning and memory have mainly used auditory cues as conditioned stimuli (CS). The present work assessed the neural network involved in olfactory fear conditioning, using olfactory bulb stimulation-induced field potential signal (EFP) as a marker of…

  14. On the organization of olfactory and vomeronasal cortices.

    PubMed

    Martinez-Marcos, Alino

    2009-01-12

    Classically, the olfactory and vomeronasal pathways are thought to run in parallel non-overlapping axes in the forebrain subserving different functions. The olfactory and vomeronasal epithelia project to the main and accessory olfactory bulbs (primary projections), which in turn project to different areas of the telencephalon in a non-topographic fashion (secondary projections) and so on (tertiary projections). New data indicate that projections arising from the main and accessory olfactory bulbs converge widely in the rostral basal telencephalon. In contrast, in the vomeronasal system, cloning two classes of vomeronasal receptors (V1R and V2R) has led to the distinction of two anatomically and functionally independent pathways that reach some common, but also some different, targets in the amygdala. Tertiary projections from the olfactory and vomeronasal amygdalae are directed to the ventral striatum, which thus becomes a site for processing and potential convergence of chemosensory stimuli. Functional data indicate that the olfactory and vomeronasal systems are able to detect and process volatiles (presumptive olfactory cues) as well as pheromones in both epithelia and bulbs. Collectively, these data indicate that the anatomical and functional distinction between the olfactory and vomeronasal systems should be re-evaluated. Specifically, the recipient cortex should be reorganized to include olfactory, vomeronasal (convergent and V1R and V2R specific areas) and mixed (olfactory and vomeronasal) chemosensory cortices. This new perspective could help to unravel olfactory and vomeronasal interactions in behavioral paradigms.

  15. Olfactory dysfunction in patients with multiple sclerosis.

    PubMed

    Li, Li-Min; Yang, Li-Na; Zhang, Lin-Jie; Fu, Ying; Li, Ting; Qi, Yuan; Wang, Jing; Zhang, Da-Qi; Zhang, Ningnannan; Liu, Jingchun; Yang, Li

    2016-06-15

    Association of changes in olfactory-related structures with olfactory function in patients with multiple sclerosis (MS) is not well understood. We used a T&T olfactometer test kit to evaluate olfactory function in 26 patients with MS and 26 age- and sex-matched healthy controls (HC). Then, Brain MRI were performed and olfactory-related structures were analyzed in these subjects. Olfactory detection and recognition threshold were significantly higher in the MS group, interestingly olfactory recognition threshold positively correlated with expanded disability status scale scores in these patients. Olfactory bulb (OB) volume reduced in patients with olfactory dysfunction (ODF). At the same time, reductions in gray matter (GM) volume were observed in the parahippocampal gyrus (PCG), amygdala, piriform cortex, and inferior frontal gyrus in patients with MS compared to HC. Atrophy of the PCG was more obvious in patients with ODF than patients without ODF and the PCG volume correlated with the olfactory recognition threshold, while no difference was found in fractional anisotropy values of tract-based spatial statistics analysis in the two groups. Olfactory function in patients with MS tends to become gradually more impaired with disability aggravation. Decreases in the volume of the OB and olfactory-related GM might provide valuable information about disease status in patients with MS with olfactory impairment. PMID:27206870

  16. Harmful effects of cadmium on olfactory system in mice.

    PubMed

    Bondier, Jean-Robert; Michel, Germaine; Propper, Alain; Badot, Pierre-Marie

    2008-10-01

    The inhalation of certain metals can result in olfactory epithelial injury, an altered sense of smell, and direct delivery of the metal from the olfactory epithelium to the olfactory bulbs and other parts of the central nervous system. The purpose of this study was to examine whether mice given an intranasal instillation of cadmium would develop altered olfactory function and to assess whether cadmium may be transported directly from the olfactory epithelium to the central nervous system. To evaluate cadmium's ability to induce anosmia and on the basis of olfactory epithelium sensitivity to metals, the aim of this study was first to study cadmium effects on the olfactory function and secondly to check whether cadmium may be transported from the nasal area to the central nervous system. After an intranasal instillation of a solution containing CdCl2 at 136 mM, we observed in treated mice: (1) a partial destruction of the olfactory epithelium, which is reduced to three or four basal cell layers followed by a progressive regeneration; (2) a loss of odor discrimination with a subsequent recovery; and (3) a cadmium uptake by olfactory bulbs demonstrated using atomic absorption spectrophotometry, but not by other parts of the central nervous system. Cadmium was delivered to the olfactory bulbs, most likely along the olfactory nerve, thereby bypassing the intact blood-brain barrier. We consider that cadmium can penetrate olfactory epithelium and hence be transported to olfactory bulbs. The olfactory route could therefore be a likely way to reach the brain and should be taken into account for occupational risk assessments for this metal.

  17. Diverse Representations of Olfactory Information in Centrifugal Feedback Projections

    PubMed Central

    Osakada, Fumitaka; Tarabrina, Anna; Kizer, Erin; Callaway, Edward M.; Gage, Fred H.; Sejnowski, Terrence J.

    2016-01-01

    Although feedback or centrifugal projections from higher processing centers of the brain to peripheral regions have long been known to play essential functional roles, the anatomical organization of these connections remains largely unknown. Using a virus-based retrograde labeling strategy and 3D whole-brain reconstruction methods, we mapped the spatial organization of centrifugal projections from two olfactory cortical areas, the anterior olfactory nucleus (AON) and the piriform cortex, to the granule cell layer of the main olfactory bulb in the mouse. Both regions are major recipients of information from the bulb and are the largest sources of feedback to the bulb, collectively constituting circuits essential for olfactory coding and olfactory behavior. We found that, although ipsilateral inputs from the AON were uniformly distributed, feedback from the contralateral AON had a strong ventral bias. In addition, we observed that centrifugally projecting neurons were spatially clustered in the piriform cortex, in contrast to the distributed feedforward axonal inputs that these cells receive from the principal neurons of the bulb. Therefore, information carried from the bulb to higher processing structures by anatomically stereotypic projections is likely relayed back to the bulb by organizationally distinct feedback projections that may reflect different coding strategies and therefore different functional roles. SIGNIFICANCE STATEMENT Principles of anatomical organization, sometimes instantiated as “maps” in the mammalian brain, have provided key insights into the structure and function of circuits in sensory systems. Generally, these characterizations focus on projections from early sensory processing areas to higher processing structures despite considerable evidence that feedback or centrifugal projections often constitute major conduits of information flow. Our results identify structure in the organization of centrifugal feedback projections to the

  18. Ca(2+)-BK channel clusters in olfactory receptor neurons and their role in odour coding.

    PubMed

    Bao, Guobin; de Jong, Daniëlle; Alevra, Mihai; Schild, Detlev

    2015-12-01

    Olfactory receptor neurons (ORNs) have high-voltage-gated Ca(2+) channels whose physiological impact has remained enigmatic since the voltage-gated conductances in this cell type were first described in the 1980s. Here we show that in ORN somata of Xenopus laevis tadpoles these channels are clustered and co-expressed with large-conductance potassium (BK) channels. We found approximately five clusters per ORN and twelve Ca(2+) channels per cluster. The action potential-triggered activation of BK channels accelerates the repolarization of action potentials and shortens interspike intervals during odour responses. This increases the sensitivity of individual ORNs to odorants. At the level of mitral cells of the olfactory bulb, odour qualities have been shown to be coded by first-spike-latency patterns. The system of Ca(2+) and BK channels in ORNs appears to be important for correct odour coding because the blockage of BK channels not only affects ORN spiking patterns but also changes the latency pattern representation of odours in the olfactory bulb.

  19. Jacketed lamp bulb envelope

    DOEpatents

    MacLennan, Donald A.; Turner, Brian P.; Gitsevich, Aleksandr; Bass, Gary K.; Dolan, James T.; Kipling, Kent; Kirkpatrick, Douglas A.; Leng, Yongzhang; Levin, Izrail; Roy, Robert J.; Shanks, Bruce; Smith, Malcolm; Trimble, William C.; Tsai, Peter

    2001-01-01

    A jacketed lamp bulb envelope includes a ceramic cup having an open end and a partially closed end, the partially closed end defining an aperture, a lamp bulb positioned inside the ceramic cup abutting the aperture, and a reflective ceramic material at least partially covering a portion of the bulb not abutting the aperture. The reflective ceramic material may substantially fill an interior volume of the ceramic cup not occupied by the bulb. The ceramic cup may include a structural feature for aiding in alignment of the jacketed lamp bulb envelope in a lamp. The ceramic cup may include an external flange about a periphery thereof. One example of a jacketed lamp bulb envelope includes a ceramic cup having an open end and a closed end, a ceramic washer covering the open end of the ceramic cup, the washer defining an aperture therethrough, a lamp bulb positioned inside the ceramic cup abutting the aperture, and a reflective ceramic material filling an interior volume of the ceramic cup not occupied by the bulb. A method of packing a jacketed lamp bulb envelope of the type comprising a ceramic cup with a lamp bulb disposed therein includes the steps of filling the ceramic cup with a flowable slurry of reflective material, and applying centrifugal force to the cup to pack the reflective material therein.

  20. Monoallelic Expression of Olfactory Receptors

    PubMed Central

    Monahan, Kevin; Lomvardas, Stavros

    2016-01-01

    The sense of smell collects vital information about the environment by detecting a multitude of chemical odorants. Breadth and sensitivity are provided by a huge number of chemosensory receptor proteins, including more than 1,400 olfactory receptors (ORs). Organizing the sensory information generated by these receptors so that it can be processed and evaluated by the central nervous system is a major challenge. This challenge is overcome by monogenic and monoallelic expression of OR genes. The single OR expressed by each olfactory sensory neuron determines the neuron’s odor sensitivity and the axonal connections it will make to downstream neurons in the olfactory bulb. The expression of a single OR per neuron is accomplished by coupling a slow chromatin-mediated activation process to a fast negative-feedback signal that prevents activation of additional ORs. Singular OR activation is likely orchestrated by a network of interchromosomal enhancer interactions and large-scale changes in nuclear architecture. PMID:26359778

  1. Olfactory system oscillations across phyla.

    PubMed

    Kay, Leslie M

    2015-04-01

    Neural oscillations are ubiquitous in olfactory systems of mammals, insects and molluscs. Neurophysiological and computational investigations point to common mechanisms for gamma or odor associated oscillations across phyla (40-100Hz in mammals, 20-30Hz in insects, 0.5-1.5Hz in molluscs), engaging the reciprocal dendrodendritic synapse between excitatory principle neurons and inhibitory interneurons in the olfactory bulb (OB), antennal lobe (AL), or procerebrum (PrC). Recent studies suggest important mechanisms that may modulate gamma oscillations, including neuromodulators and centrifugal input to the OB and AL. Beta (20Hz) and theta (2-12Hz) oscillations coordinate activity within and across brain regions. Olfactory beta oscillations are associated with odor learning and depend on centrifugal OB input, while theta oscillations are strongly associated with respiration.

  2. Interactions with the young down-regulate adult olfactory neurogenesis and enhance the maturation of olfactory neuroblasts in sheep mothers

    PubMed Central

    Brus, Maïna; Meurisse, Maryse; Keller, Matthieu; Lévy, Frédéric

    2014-01-01

    New neurons are continuously added in the dentate gyrus (DG) and the olfactory bulb of mammalian brain. While numerous environmental factors controlling survival of newborn neurons have been extensively studied, regulation by social interactions is less documented. We addressed this question by investigating the influence of parturition and interactions with the young on neurogenesis in sheep mothers. Using Bromodeoxyuridine, a marker of cell division, in combination with markers of neuronal maturation, the percentage of neuroblasts and new mature neurons in the olfactory bulb and the DG was compared between groups of parturient ewes which could interact or not with their lamb, and virgins. In addition, a morphological analysis was performed by measuring the dendritic arbor of neuroblasts in both structures. We showed that the postpartum period was associated with a decrease in olfactory and hippocampal adult neurogenesis. In the olfactory bulb, the suppressive effect on neuroblasts was dependent on interactions with the young whereas in the DG the decrease in new mature neurons was associated with parturition. In addition, dendritic length and number of nodes of neuroblasts were significantly enhanced by interactions with the lamb in the olfactory bulb but not in the DG. Because interactions with the young involved learning of the olfactory signature of the lamb, we hypothesize that this learning is associated with a down-regulation in olfactory neurogenesis and an enhancement of olfactory neuroblast maturation. Our assumption is that fewer new neurons decrease cell competition in the olfactory bulb and enhance maturation of those new neurons selected to participate in the learning of the young odor. PMID:24600367

  3. Blood supply of the olfactory nerve. Meningeal relationships and surgical relevance.

    PubMed

    Favre, J J; Chaffanjon, P; Passagia, J G; Chirossel, J P

    1995-01-01

    The authors report the results of a series of dissections and anatomic sections of the fronto-basal region of the brain and of the anterior cranial fossa in human cadavers. The constant presence of an arachnoidal cistern above the olfactory nerve was verified. The arachnoid separates from the pial membrane and forms a bridge with the ventral part of the olfactory bulb and tract, from the lateral edge of the olfactory sulcus to the medial edge of the gyrus rectus. The cistern is wide in its anterior portion, between the gyrus rectus and the olfactory bulb, and is reduced to a virtual slit in its posterior portion where the tract is lodged in the olfactory sulcus. The olfactory nerve can be separated without damaging fronto-basal arachnoidial adhesions over several centimeters. Dissection of this region after intravascular injection of colored media shows the constant presence of an artery destined to the olfactory bulb and tract. It originates either from the lateral surface of the anterior cerebral a. (segment A2), or from the medial fronto-basal a., and consistently provides terminal branches in front of the olfactory trigone in the medial olfactory sulcus. At their ventral extremity, the olfactory structures are therefore vascularised independently for several centimeters, from the lower face of the frontal lobe. The independent vascularisation of the olfactory nerve, the tenuous and easily detachable adhesions, and the actual presence of a true arachnoidal cistern all contribute to enabling surgical techniques which conserve olfactory function during anterior approaches. PMID:7482150

  4. Nasal toxicity, carcinogenicity, and olfactory uptake of metals.

    PubMed

    Sunderman, F W

    2001-01-01

    Occupational exposures to inhalation of certain metal dusts or aerosols can cause loss of olfactory acuity, atrophy of the nasal mucosa, mucosal ulcers, perforated nasal septum, or sinonasal cancer. Anosmia and hyposmia have been observed in workers exposed to Ni- or Cd-containing dusts in alkaline battery factories, nickel refineries, and cadmium industries. Ulcers of the nasal mucosa and perforated nasal septum have been reported in workers exposed to Cr(VI) in chromate production and chrome plating, or to As(III) in arsenic smelters. Atrophy of the olfactory epithelium has been observed in rodents following inhalation of NiSO4 or alphaNi3S2. Cancers of the nose and nasal sinuses have been reported in workers exposed to Ni compounds in nickel refining, cutlery factories, and alkaline battery manufacture, or to Cr(VI) in chromate production and chrome plating. In animals, several metals (eg, Al, Cd, Co, Hg, Mn, Ni, Zn) have been shown to pass via olfactory receptor neurons from the nasal lumen through the cribriform plate to the olfactory bulb. Some metals (eg, Mn, Ni, Zn) can cross synapses in the olfactory bulb and migrate via secondary olfactory neurons to distant nuclei of the brain. After nasal instillation of a metal-containing solution, transport of the metal via olfactory axons can occur rapidly, within hours or a few days (eg, Mn), or slowly over days or weeks (eg, Ni). The olfactory bulb tends to accumulate certain metals (eg, Al, Bi, Cu, Mn, Zn) with greater avidity than other regions of the brain. The molecular mechanisms responsible for metal translocation in olfactory neurons and deposition in the olfactory bulb are unclear, but complexation by metal-binding molecules such as carnosine (beta-alanyl-L-histidine) may be involved. PMID:11314863

  5. Anatomy, histochemistry, and immunohistochemistry of the olfactory subsystems in mice

    PubMed Central

    Barrios, Arthur W.; Núñez, Gonzalo; Sánchez Quinteiro, Pablo; Salazar, Ignacio

    2014-01-01

    The four regions of the murine nasal cavity featuring olfactory neurons were studied anatomically and by labeling with lectins and relevant antibodies with a view to establishing criteria for the identification of olfactory subsystems that are readily applicable to other mammals. In the main olfactory epithelium and the septal organ the olfactory sensory neurons (OSNs) are embedded in quasi-stratified columnar epithelium; vomeronasal OSNs are embedded in epithelium lining the medial interior wall of the vomeronasal duct and do not make contact with the mucosa of the main nasal cavity; and in Grüneberg's ganglion a small isolated population of OSNs lies adjacent to, but not within, the epithelium. With the exception of Grüneberg's ganglion, all the tissues expressing olfactory marker protein (OMP) (the above four nasal territories, the vomeronasal and main olfactory nerves, and the main and accessory olfactory bulbs) are also labeled by Lycopersicum esculentum agglutinin, while Ulex europaeus agglutinin I labels all and only tissues expressing Gαi2 (the apical sensory neurons of the vomeronasal organ, their axons, and their glomerular destinations in the anterior accessory olfactory bulb). These staining patterns of UEA-I and LEA may facilitate the characterization of olfactory anatomy in other species. A 710-section atlas of the anatomy of the murine nasal cavity has been made available on line. PMID:25071468

  6. The Pig Olfactory Brain: A Primer

    PubMed Central

    Feldman, Sanford; Osterberg, Stephen K.

    2016-01-01

    Despite the fact that pigs are reputed to have excellent olfactory abilities, few studies have examined regions of the pig brain involved in the sense of smell. The present study provides an overview of the olfactory bulb, anterior olfactory nucleus, and piriform cortex of adult pigs using several approaches. Nissl, myelin, and Golgi stains were used to produce a general overview of the organization of the regions and confocal microscopy was employed to examine 1) projection neurons, 2) GABAergic local circuit neurons that express somatostatin, parvalbumin, vasoactive intestinal polypeptide, or calretinin, 3) neuromodulatory fibers (cholinergic and serotonergic), and 4) glia (astrocytes and microglia). The findings revealed that pig olfactory structures are quite large, highly organized and follow the general patterns observed in mammals. PMID:26936231

  7. The Pig Olfactory Brain: A Primer.

    PubMed

    Brunjes, Peter C; Feldman, Sanford; Osterberg, Stephen K

    2016-06-01

    Despite the fact that pigs are reputed to have excellent olfactory abilities, few studies have examined regions of the pig brain involved in the sense of smell. The present study provides an overview of the olfactory bulb, anterior olfactory nucleus, and piriform cortex of adult pigs using several approaches. Nissl, myelin, and Golgi stains were used to produce a general overview of the organization of the regions and confocal microscopy was employed to examine 1) projection neurons, 2) GABAergic local circuit neurons that express somatostatin, parvalbumin, vasoactive intestinal polypeptide, or calretinin, 3) neuromodulatory fibers (cholinergic and serotonergic), and 4) glia (astrocytes and microglia). The findings revealed that pig olfactory structures are quite large, highly organized and follow the general patterns observed in mammals. PMID:26936231

  8. Motors and Bulbs in Series

    ERIC Educational Resources Information Center

    Whitaker, Robert J.

    2009-01-01

    One of Paul Hewitt's "Figuring Physics" that appeared in this journal dealt with the heating of a motor. This phenomenon can be demonstrated with a miniature motor and a bulb as part of a series of activities with "batteries and bulbs." Students examine the effect on the brightness of a single bulb when a second, identical bulb is placed in series…

  9. Experimenting with Bulbs

    NASA Astrophysics Data System (ADS)

    Cavicchi, Elizabeth M.

    1998-04-01

    What questions come about as learners explore physical materials? How does their learning deepen through inventing experiments and making and testing their own interpretations? I present episodes from the investigatory work of three adult learners who met regularly with me to explore batteries, bulbs and wires. I taught by engaging the learners' interest in these materials and by interactively researching their developing understandings. As both teacher and researcher, I used what I learned about their understandings to support their efforts to extend the body of experimental knowledge they were developing. Development is evident in experimental details. Initially, by hand-holding, they light a bulb with a wire and battery. Later, in soldering connections, they wonder about the bulb's internal structure. They research thoughts about this through dissecting a bulb -- and lighting its exposed filament. Such experimenting changed thinking: from imagining sequential loops, to questioning electrical contacts, to inferring circuital paths.

  10. Structure and function of long-lived olfactory organotypic cultures from postnatal mice.

    PubMed

    Josephson, E M; Yilma, S; Vodyanoy, V; Morrison, E E

    2004-03-01

    The first synapse in the olfactory pathway mediates a significant transfer of information given the restricted association of specific olfactory receptor neurons with specific glomeruli in the olfactory bulb. To understand better how this connection is made and what the functional capacities of the participating cells are, we created a long-lived culture system composed of olfactory epithelium and olfactory bulb tissues. Using the roller tube method of culturing, we grew epithelium-bulb cocultures, explanted from 1-4-day-old Swiss Webster mice, on Aclar for periods ranging from 18 hr to 68 days. The explants flattened so that in some areas the culture was only a few cells thick, making individual cells distinguishable. From 107 cultures studied, we identified the following cell types by expression of specific markers (oldest culture expressing marker, days in vitro, DIV): olfactory receptor neurons (neural cell adhesion molecule, 42 DIV); mature receptor neurons (olfactory marker protein, 28 DIV); postmitotic olfactory receptor neurons and olfactory bulb neurons (beta-tubulin, 68 DIV); astrocytes (glial fibrillary acidic protein, glutamate/aspartate transporter, 68 DIV); olfactory horizontal basal cells (cytokeratin, 22 DIV). Neuronal processes formed glomeruli in 2-4-week-old cultures. We also recorded electro-olfactography responses to puffs of vapor collected over an odorant mixture containing ethyl butyrate, eugenol, (+) carvone, and (-) carvone from cultures as old as 21 DIV. These features of our olfactory culture system make this model useful for studying properties of immature and mature olfactory receptor neurons, pathfinding strategies of receptor axons, and mechanisms of information transfer in the olfactory glomerulus.

  11. Brain-derived neurotrophic factor (BDNF) expression in normal and regenerating olfactory epithelium of Xenopus laevis.

    PubMed

    Frontera, Jimena Laura; Cervino, Ailen Soledad; Jungblut, Lucas David; Paz, Dante Agustín

    2015-03-01

    Olfactory epithelium has the capability to continuously regenerate olfactory receptor neurons throughout life. Adult neurogenesis results from proliferation and differentiation of neural stem cells, and consequently, olfactory neuroepithelium offers an excellent opportunity to study neural regeneration and the factors involved in the maintenance and regeneration of all their cell types. We analyzed the expression of BDNF in the olfactory system under normal physiological conditions as well as during a massive regeneration induced by chemical destruction of the olfactory epithelium in Xenopus laevis larvae. We described the expression and presence of BDNF in the olfactory epithelium and bulb. In normal physiological conditions, sustentacular (glial) cells and a few scattered basal (stem) cells express BDNF in the olfactory epithelium as well as the granular cells in the olfactory bulb. Moreover, during massive regeneration, we demonstrated a drastic increase in basal cells expressing BDNF as well as an increase in BDNF in the olfactory bulb and nerve. Together these results suggest an important role of BDNF in the maintenance and regeneration of the olfactory system.

  12. Solar light bulb

    SciTech Connect

    Smith, D.A.

    1983-07-26

    A system for generating light directly using solar energy is provided herein. It includes a concentrator and accumulator for the sun's rays to generate a concentrated beam of visible solar radiation. A distributor shaft is provided for distributing the beam of visible solar radiation. A fork is provided in the distributor shaft to define a plurality of branch lines, each provided with a mirror at the intersection to direct the beam down the respective branch line to permit parallel fractions of the beam to be reflected off the respective mirrors and to pass down the respective branch line. A solar bulb is provided including a double walled upper bulbous portion including the inlet from the branch line and a pair of heat outlet tubes, and a double walled lower bulbous portion, the upper portion thereof being divergently reflective, with the lower portion having walls which are either transparent or translucent to provide greater light diffusion, and the space between the two walls being maintained under vacuum to provide heat insulation values. A structure is provided within the solar bulb for the absorption and radiation of the concentrated beam of visible solar radiation. Preferably structure is provided connected to the solar bulb to draw in outside air in the summer to direct it past the solar bulb and to air vent hot air produced at the solar bulb to the outside, thereby providing light with minimal heat in the summer. The same structure is operated in the winter to draw in household air to direct it past the solar bulb and to recirculate such heated air produced at the solar bulb to the house, thereby providing light and heat in the winter.

  13. What a Nostril Knows: Olfactory Nerve-Evoked AMPA Responses Increase while NMDA Responses Decrease at 24-h Post-Training for Lateralized Odor Preference Memory in Neonate Rat

    ERIC Educational Resources Information Center

    Yuan, Qi; Harley, Carolyn W.

    2012-01-01

    Increased AMPA signaling is proposed to mediate long-term memory. Rat neonates acquire odor preferences in a single olfactory bulb if one nostril is occluded at training. Memory testing here confirmed that only trained bulbs support increased odor preference at 24 h. Olfactory nerve field potentials were tested at 24 h in slices from trained and…

  14. Convergence of olfactory and vomeronasal projections in the rat basal telencephalon.

    PubMed

    Pro-Sistiaga, Palma; Mohedano-Moriano, Alicia; Ubeda-Bañon, Isabel; Del Mar Arroyo-Jimenez, Maria; Marcos, Pilar; Artacho-Pérula, Emilio; Crespo, Carlos; Insausti, Ricardo; Martinez-Marcos, Alino

    2007-10-01

    Olfactory and vomeronasal projections have been traditionally viewed as terminating in contiguous non-overlapping areas of the basal telencephalon. Original reports, however, described areas such as the anterior medial amygdala where both chemosensory afferents appeared to overlap. We addressed this issue by injecting dextran amines in the main or accessory olfactory bulbs of rats and the results were analyzed with light and electron microscopes. Simultaneous injections of different fluorescent dextran amines in the main and accessory olfactory bulbs were performed and the results were analyzed using confocal microscopy. Similar experiments with dextran amines in the olfactory bulbs plus FluoroGold in the bed nucleus of the stria terminalis indicate that neurons projecting through the stria terminalis could be integrating olfactory and vomeronasal inputs. Retrograde tracing experiments using FluoroGold or dextran amines confirm that areas of the rostral basal telencephalon receive inputs from both the main and accessory olfactory bulbs. While both inputs clearly converge in areas classically considered olfactory-recipient (nucleus of the lateral olfactory tract, anterior cortical amygdaloid nucleus, and cortex-amygdala transition zone) or vomeronasal-recipient (ventral anterior amygdala, bed nucleus of the accessory olfactory tract, and anteroventral medial amygdaloid nucleus), segregation is virtually complete at posterior levels such as the posteromedial and posterolateral cortical amygdalae. This provides evidence that areas so far considered receiving a single chemosensory modality are likely sites for convergent direct olfactory and vomeronasal inputs. Therefore, areas of the basal telencephalon should be reclassified as olfactory, vomeronasal, or mixed chemosensory structures, which could facilitate understanding of olfactory-vomeronasal interactions in functional studies.

  15. Illuminating Physics with Light Bulbs.

    ERIC Educational Resources Information Center

    Leff, Harvey S.

    1990-01-01

    Presents ideas on how common household light bulbs can be used to develop interest in learning physics. Focuses on supermarket data taking and analyses, filament temperatures, detective work with three-way bulbs, and lifetime statistics. (YP)

  16. Tract-tracing study of the extrabulbar olfactory projections in the brain of some teleosts.

    PubMed

    D'aniello, Biagio; Luongo, Luciano; Rastogi, Rakesh K; Di Meglio, Maria; Pinelli, Claudia

    2015-04-01

    The extrabulbar olfactory projections (EBOP) is a collection of nerve fibers that originate from primary olfactory receptor neurons. These fibers penetrate into the brain, bypassing the olfactory bulbs (OBs). While the presence of an EBOP has been well established in teleosts, here we morphologically characterize the EBOP structure in four species each with a different morphological relationship of OB with the ventral telencephalic area. Tract-tracing methods (carbocyanine DiI/DIA and biocytin) were used. FMRFamide immunoreactive nervus terminalis (NT) components were also visualized to define any neuroanatomical relationship between the NT and EBOP. Unilateral DiI/DiA application to the olfactory chamber stained the entire olfactory epithelium, olfactory nerve fibers, and ipsilateral olfactory bulb. Labeled primary olfactory fibers running ventromedially as extrabulbar primary olfactory projections reached various regions of the secondary prosencephalon. Only in Moenkhausia sanctaefilomenae (no olfactory peduncle) did lipophilic tracer-labeled fibers reach the ipsilateral mesencephalon. The combination of tracing techniques and FMRFamide immunohistochemistry revealed a substantial overlap of the label along the olfactory pathways as well as in the anterior secondary prosencephalon. However, FMRFamide immunoreactivity was never colocalized in the same cellular or fiber component as visualized using tracer molecules. Our results showed a certain uniformity in the neuroanatomy and extension of EBOP in all four species, independent of the pedunculate feature of the OBs. The present study also provided additional evidence to support the view that EBOP and FMRFamide immunoreactive components of the NT are separate anatomical entities. PMID:25663434

  17. Olfactory deposition of inhaled nanoparticles in humans

    PubMed Central

    Garcia, Guilherme J. M.; Schroeter, Jeffry D.; Kimbell, Julia S.

    2016-01-01

    Context Inhaled nanoparticles can migrate to the brain via the olfactory bulb, as demonstrated in experiments in several animal species. This route of exposure may be the mechanism behind the correlation between air pollution and human neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. Objectives This manuscript aims to (1) estimate the dose of inhaled nanoparticles that deposit in the human olfactory epithelium during nasal breathing at rest and (2) compare the olfactory dose in humans with our earlier dose estimates for rats. Materials and methods An anatomically-accurate model of the human nasal cavity was developed based on computed tomography scans. The deposition of 1–100 nm particles in the whole nasal cavity and its olfactory region were estimated via computational fluid dynamics (CFD) simulations. Our CFD methods were validated by comparing our numerical predictions for whole-nose deposition with experimental data and previous CFD studies in the literature. Results In humans, olfactory dose of inhaled nanoparticles is highest for 1–2 nm particles with approximately 1% of inhaled particles depositing in the olfactory region. As particle size grows to 100 nm, olfactory deposition decreases to 0.01% of inhaled particles. Discussion and conclusion Our results suggest that the percentage of inhaled particles that deposit in the olfactory region is lower in humans than in rats. However, olfactory dose per unit surface area is estimated to be higher in humans due to their larger minute volume. These dose estimates are important for risk assessment and dose-response studies investigating the neurotoxicity of inhaled nanoparticles. PMID:26194036

  18. The development of the olfactory organs in newly hatched monotremes and neonate marsupials.

    PubMed

    Schneider, Nanette Yvette

    2011-08-01

    Olfactory cues are thought to play a crucial role in the detection of the milk source at birth in mammals. It has been shown that a marsupial, the tammar wallaby, can detect olfactory cues from its mother's pouch at birth. This study investigates whether the main olfactory and accessory olfactory system are similarly well developed in other marsupials and monotremes at birth/hatching as in the tammar. Sections of the head of various marsupial and two monotreme species were investigated by light microscopy. Both olfactory systems were less well developed in the kowari and Eastern quoll. No olfactory or vomeronasal or terminal nerves could be observed; the main olfactory bulb (MOB) had only two layers while no accessory olfactory bulb or ganglion terminale were visible. All other investigated marsupials and monotremes showed further developed olfactory systems with olfactory, vomeronasal and terminal nerves, a three-layered MOB, and in the marsupials a prominent ganglion terminale. The main olfactory system was further developed than the accessory olfactory system in all species investigated. The olfactory systems were the least developed in species in which the mother's birth position removed most of the difficulty in reaching the teat, placing the neonate directly in the pouch. In monotremes they were the furthest developed as Bowman glands were found underlying the main olfactory epithelium. This may reflect the need to locate the milk field each time they drink as they cannot permanently attach to it, unlike therian mammals. While it still needs to be determined how an odour signal could be further processed in the brain, this study suggests that marsupials and monotremes possess well enough developed olfactory systems to be able to detect an odour cue from the mammary area at birth/hatching. It is therefore likely that neonate marsupials and newly hatched monotremes find their way to the milk source using olfactory cues, as has been previously suggested for the

  19. The development of the olfactory organs in newly hatched monotremes and neonate marsupials

    PubMed Central

    Schneider, Nanette Yvette

    2011-01-01

    Olfactory cues are thought to play a crucial role in the detection of the milk source at birth in mammals. It has been shown that a marsupial, the tammar wallaby, can detect olfactory cues from its mother's pouch at birth. This study investigates whether the main olfactory and accessory olfactory system are similarly well developed in other marsupials and monotremes at birth/hatching as in the tammar. Sections of the head of various marsupial and two monotreme species were investigated by light microscopy. Both olfactory systems were less well developed in the kowari and Eastern quoll. No olfactory or vomeronasal or terminal nerves could be observed; the main olfactory bulb (MOB) had only two layers while no accessory olfactory bulb or ganglion terminale were visible. All other investigated marsupials and monotremes showed further developed olfactory systems with olfactory, vomeronasal and terminal nerves, a three-layered MOB, and in the marsupials a prominent ganglion terminale. The main olfactory system was further developed than the accessory olfactory system in all species investigated. The olfactory systems were the least developed in species in which the mother's birth position removed most of the difficulty in reaching the teat, placing the neonate directly in the pouch. In monotremes they were the furthest developed as Bowman glands were found underlying the main olfactory epithelium. This may reflect the need to locate the milk field each time they drink as they cannot permanently attach to it, unlike therian mammals. While it still needs to be determined how an odour signal could be further processed in the brain, this study suggests that marsupials and monotremes possess well enough developed olfactory systems to be able to detect an odour cue from the mammary area at birth/hatching. It is therefore likely that neonate marsupials and newly hatched monotremes find their way to the milk source using olfactory cues, as has been previously suggested for the

  20. The development of the olfactory organs in newly hatched monotremes and neonate marsupials.

    PubMed

    Schneider, Nanette Yvette

    2011-08-01

    Olfactory cues are thought to play a crucial role in the detection of the milk source at birth in mammals. It has been shown that a marsupial, the tammar wallaby, can detect olfactory cues from its mother's pouch at birth. This study investigates whether the main olfactory and accessory olfactory system are similarly well developed in other marsupials and monotremes at birth/hatching as in the tammar. Sections of the head of various marsupial and two monotreme species were investigated by light microscopy. Both olfactory systems were less well developed in the kowari and Eastern quoll. No olfactory or vomeronasal or terminal nerves could be observed; the main olfactory bulb (MOB) had only two layers while no accessory olfactory bulb or ganglion terminale were visible. All other investigated marsupials and monotremes showed further developed olfactory systems with olfactory, vomeronasal and terminal nerves, a three-layered MOB, and in the marsupials a prominent ganglion terminale. The main olfactory system was further developed than the accessory olfactory system in all species investigated. The olfactory systems were the least developed in species in which the mother's birth position removed most of the difficulty in reaching the teat, placing the neonate directly in the pouch. In monotremes they were the furthest developed as Bowman glands were found underlying the main olfactory epithelium. This may reflect the need to locate the milk field each time they drink as they cannot permanently attach to it, unlike therian mammals. While it still needs to be determined how an odour signal could be further processed in the brain, this study suggests that marsupials and monotremes possess well enough developed olfactory systems to be able to detect an odour cue from the mammary area at birth/hatching. It is therefore likely that neonate marsupials and newly hatched monotremes find their way to the milk source using olfactory cues, as has been previously suggested for the

  1. The sense of smell: multiple olfactory subsystems.

    PubMed

    Breer, H; Fleischer, J; Strotmann, J

    2006-07-01

    The mammalian olfactory system is not uniformly organized but consists of several subsystems each of which probably serves distinct functions. Not only are the two major nasal chemosensory systems, the vomeronasal organ and the main olfactory epithelium, structurally and functionally separate entities, but the latter is further subcompartimentalized into overlapping expression zones and projection-related subzones. Moreover, the populations of 'OR37' neurons not only express a unique type of olfactory receptors but also are segregated in a cluster-like manner and generally project to only one receptor-specific glomerulus. The septal organ is an island of sensory epithelium on the nasal septum positioned at the nasoplatine duct; it is considered as a 'mini-nose' with dual function. A specific chemosensory function of the most recently discovered subsystem, the so-called Grueneberg ganglion, is based on the expression of olfactory marker protein and the axonal projections to defined glomeruli within the olfactory bulb. This complexity of distinct olfactory subsystems may be one of the features determining the enormous chemosensory capacity of the sense of smell.

  2. Adult Neurogenesis and the Olfactory System

    PubMed Central

    Whitman, Mary C.; Greer, Charles A.

    2009-01-01

    Though initially described in the early 1960s, it is only within the past decade that the concept of continuing adult neurogenesis has gained widespread acceptance. Neuroblasts from the subventricular zone (SVZ) migrate along the rostral migratory stream (RMS) into the olfactory bulb, where they differentiate into interneurons. Neuroblasts from the subgranular zone (SGZ) of the hippocampal formation show relatively little migratory behavior, and differentiate into dentate gyrus granule cells. In sharp contrast to embryonic and perinatal development, these newly differentiated neurons must integrate into a fully functional circuit, without disrupting ongoing performance. Here, after a brief historical overview and introduction to olfactory circuitry, we review recent advances in the biology of neural stem cells, mechanisms of migration in the RMS and olfactory bulb, differentiation and survival of new neurons, and finally mechanisms of synaptic integration. Our primary focus is on the olfactory system, but we also contrast the events occurring there with those in the hippocampal formation. Although both SVZ and SGZ neurogenesis are involved in some types of learning, their full functional significance remains unclear. Since both systems offer models of integration of new neuroblasts, there is immense interest in using neural stem cells to replace neurons lost in injury or disease. Though many questions remain unanswered, new insights appear daily about adult neurogenesis, regulatory mechanisms, and the fates of the progeny. We discuss here some of the central features of these advances, as well as speculate on future research directions. PMID:19615423

  3. Cladistic Analysis of Olfactory and Vomeronasal Systems

    PubMed Central

    Ubeda-Bañon, Isabel; Pro-Sistiaga, Palma; Mohedano-Moriano, Alicia; Saiz-Sanchez, Daniel; de la Rosa-Prieto, Carlos; Gutierrez-Castellanos, Nicolás; Lanuza, Enrique; Martinez-Garcia, Fernando; Martinez-Marcos, Alino

    2010-01-01

    Most tetrapods possess two nasal organs for detecting chemicals in their environment, which are the sensory detectors of the olfactory and vomeronasal systems. The seventies’ view that the olfactory system was only devoted to sense volatiles, whereas the vomeronasal system was exclusively specialized for pheromone detection was challenged by accumulating data showing deep anatomical and functional interrelationships between both systems. In addition, the assumption that the vomeronasal system appeared as an adaptation to terrestrial life is being questioned as well. The aim of the present work is to use a comparative strategy to gain insight in our understanding of the evolution of chemical “cortex.” We have analyzed the organization of the olfactory and vomeronasal cortices of reptiles, marsupials, and placental mammals and we have compared our findings with data from other taxa in order to better understand the evolutionary history of the nasal sensory systems in vertebrates. The olfactory and vomeronsasal cortices have been re-investigated in garter snakes (Thamnophis sirtalis), short-tailed opossums (Monodelphis domestica), and rats (Rattus norvegicus) by tracing the efferents of the main and accessory olfactory bulbs using injections of neuroanatomical anterograde tracers (dextran-amines). In snakes, the medial olfactory tract is quite evident, whereas the main vomeronasal-recipient structure, the nucleus sphaericus is a folded cortical-like structure, located at the caudal edge of the amygdala. In marsupials, which are acallosal mammals, the rhinal fissure is relatively dorsal and the olfactory and vomeronasal cortices relatively expanded. Placental mammals, like marsupials, show partially overlapping olfactory and vomeronasal projections in the rostral basal telencephalon. These data raise the interesting question of how the telencephalon has been re-organized in different groups according to the biological relevance of chemical senses. PMID:21290004

  4. Cladistic analysis of olfactory and vomeronasal systems.

    PubMed

    Ubeda-Bañon, Isabel; Pro-Sistiaga, Palma; Mohedano-Moriano, Alicia; Saiz-Sanchez, Daniel; de la Rosa-Prieto, Carlos; Gutierrez-Castellanos, Nicolás; Lanuza, Enrique; Martinez-Garcia, Fernando; Martinez-Marcos, Alino

    2011-01-01

    Most tetrapods possess two nasal organs for detecting chemicals in their environment, which are the sensory detectors of the olfactory and vomeronasal systems. The seventies' view that the olfactory system was only devoted to sense volatiles, whereas the vomeronasal system was exclusively specialized for pheromone detection was challenged by accumulating data showing deep anatomical and functional interrelationships between both systems. In addition, the assumption that the vomeronasal system appeared as an adaptation to terrestrial life is being questioned as well. The aim of the present work is to use a comparative strategy to gain insight in our understanding of the evolution of chemical "cortex." We have analyzed the organization of the olfactory and vomeronasal cortices of reptiles, marsupials, and placental mammals and we have compared our findings with data from other taxa in order to better understand the evolutionary history of the nasal sensory systems in vertebrates. The olfactory and vomeronsasal cortices have been re-investigated in garter snakes (Thamnophis sirtalis), short-tailed opossums (Monodelphis domestica), and rats (Rattus norvegicus) by tracing the efferents of the main and accessory olfactory bulbs using injections of neuroanatomical anterograde tracers (dextran-amines). In snakes, the medial olfactory tract is quite evident, whereas the main vomeronasal-recipient structure, the nucleus sphaericus is a folded cortical-like structure, located at the caudal edge of the amygdala. In marsupials, which are acallosal mammals, the rhinal fissure is relatively dorsal and the olfactory and vomeronasal cortices relatively expanded. Placental mammals, like marsupials, show partially overlapping olfactory and vomeronasal projections in the rostral basal telencephalon. These data raise the interesting question of how the telencephalon has been re-organized in different groups according to the biological relevance of chemical senses.

  5. Nuclear light bulb

    NASA Technical Reports Server (NTRS)

    Latham, Tom

    1991-01-01

    The nuclear light bulb engine is a closed cycle concept. The nuclear light bulb concept provides containment by keeping the nuclear fuel fluid mechanically suspended in a cylindrical geometry. Thermal heat passes through an internally cooled, fused-silica, transparent wall and heats hydrogen propellant. The seeded hydrogen propellant absorbs radiant energy and is expanded through a nozzle. Internal moderation was used in the configuration which resulted in a reduced critical density requirement. This result was supported by criticality experiments. A reference engine was designed that had seven cells and was sized to fit in what was then predicted to be the shuttle bay mass and volume limitations. There were studies done of nozzle throat cooling schemes to remove the radiant heat. Elements of the nuclear light bulb program included closed loop critical assembly tests done at Los Alamos with UF6 confined by argon buffer gas. It was shown that the fuel region could be seeded with constituents that would block UV radiation from the uranium plasma. A combination of calculations and experiments showed that internal moderation produced a critical mass reduction. Other aspects of the research are presented.

  6. Reproductive responses to photoperiod persist in olfactory bulbectomized Siberian hamsters (Phodopus sungorus).

    PubMed

    Prendergast, Brian J; Pyter, Leah M; Galang, Jerome; Kay, Leslie M

    2009-03-01

    In reproductively photoperiodic Syrian hamsters, removal of the olfactory bulbs (OBx) leads to a marked and sustained increase in gonadotrophin secretion which prevents normal testicular regression in short photoperiods. In contrast, among reproductively nonphotoperiodic laboratory strains of rats and mice, bulbectomy unmasks reproductive responses to photoperiod. The role of the olfactory bulbs has been proposed to have opposite effects on responsiveness to photoperiod, depending on the photoperiodicity of the reproductive system; however, Syrian hamsters are the only reproductively photoperiodic rodent species for which the role of the olfactory bulb in reproductive endocrinology has been assessed. This experiment evaluated the role of the olfactory bulbs in the photoperiodic control of reproduction in Siberian hamsters (Phodopus sungorus), an established model species for the study of neural substrates mediating seasonality. Relative to control hamsters housed in long days (15 h light/day), exposure of adult male hamsters to short days (9h light/day) for 8 weeks led to a temporal expansion of the pattern of nocturnal locomotor activity, testicular regression, decreases in testosterone (T) production, and undetectable levels of plasma follicle-stimulating hormone (FSH). Bilateral olfactory bulbectomy failed to affect any of these responses to short days. The patterns of entrainment to long and short days suggests that pre-pineal mechanisms involved in photoperiodic timekeeping are functioning normally in OBx hamsters. The absence of increases in FSH following bulbectomy in long days is incompatible with the hypothesis that the olfactory bulbs provide tonic inhibition of the HPG axis in this species. In marked contrast to Syrian hamsters, the olfactory bulbs of Siberian hamsters play essentially no role in the modulation of tonic gonadotrophin production or gonadotrophin responses to photoperiod.

  7. The rostral migratory stream and olfactory system: smell, disease and slippery cells.

    PubMed

    Curtis, Maurice A; Monzo, Hector J; Faull, Richard L M

    2009-01-01

    In the mammalian brain, olfaction is an important sense that is used to detect odors of different kinds that can warn of off food, to produce a mothering instinct in a flock or group of animals, and to warn of danger such as fire or poison. The olfactory system is made up of a long-distance rostral migratory stream that arises from the subventricular zone in the wall of the lateral ventricle, mainly comprises neuroblasts, and stretches all the way through the basal forebrain to terminate in the olfactory bulb. The olfactory bulb receives a constant supply of new neurons that allow ongoing integration of new and different smells, and these are integrated into either the granule cell layer or the periglomerular layer. The continuous turnover of neurons in the olfactory bulb allows us to study the proliferation, migration, and differentiation of neurons and their application in therapies for neurodegenerative diseases. In this chapter, we will examine the notion that the olfactory system might be the route of entry for factors that cause or contribute to neurodegeneration in the central nervous system. We will also discuss the enzymes that may be involved in the addition of polysialic acid to neural cell adhesion molecule, which is vital for allowing the neuroblasts to move through the rostral migratory stream. Finally, we will discuss a possible role of endosialidases for removing polysialic acid from neural cell adhesion molecules, which causes neuroblasts to stop migrating and terminally differentiate into olfactory bulb interneurons.

  8. Microvasculature of the Olfactory Organ in the Japanese Monkey (Macaca fuscata fuscata)

    NASA Astrophysics Data System (ADS)

    Okada, Shigenori; Schraufnagel, Dean E.

    2002-06-01

    Olfaction is an important and primitive sense. As its importance has changed with evolution, anatomic adjustments have occurred in its structure and vasculature. Primates are a family of vertebrates that have had to develop their visual system to adapt to the arboreal environment and have evolved from a macrosmatic to a microsmatic species as the optic system has enlarged. This has resulted in anatomic changes of a small but critical area at the base of the brain. This paper describes the three-dimensional vascular anatomy of the olfactory organ of the Japanese monkey (Macaca fuscata fuscata). This is best understood by dividing the organ into three parts: the olfactory tract, olfactory bulb, and olfactory nerves in the nasal mucosa. The bulb can be partitioned into an outer or cortical part and inner or medullary part. The vasculature and tissue were examined grossly and with light microscopy and scanning electron microscopy of vascular corrosion casts. The olfactory tract and bulb were supplied by an arteriole from the anterior cerebral artery on each side. The tract was supplied by capillaries running spirally with a coarse network. At the olfactory bulb, the arteriole ramified into the intracortical and medullary branches that formed capillary networks. The bulbar intracortical capillaries were divided into two layers with different densities and vascular patterns. The capillaries of the superficial layer had a ladder-like pattern. The branches that ran into the medulla of the olfactory bulb were more widely spaced. Twigs from the posterior ethmoidal artery ran along the nerve fiber and formed intra- and extrafascicular networks. Each region of the olfactory organ had characteristic three-dimensional vascular patterns that were related to their cellular architecture.

  9. Chemical olfactory signals and parenthood in mammals.

    PubMed

    Corona, Rebeca; Lévy, Frédéric

    2015-02-01

    This article is part of a Special Issue "Chemosignals and Reproduction". In mammalian species, odor cues emitted by the newborn are essential to establish maternal behavior at parturition and coordinate early mother-infant interactions. Offspring odors become potent attractive stimuli at parturition promoting the contact with the young to ensure that normal maternal care develops. In some species odors provide a basis for individual recognition of the offspring and highly specialized neural mechanisms for learning the infant signals have evolved. Both the main and the accessory olfactory systems are involved in the onset of maternal care, but only the former contributes to individual odor discrimination of the young. Electrophysiological and neurochemical changes occur in the main olfactory bulb leading to a coding of the olfactory signature of the familiar young. Olfactory neurogenesis could also contribute to motherhood and associated learning. Parturition and interactions with the young influence neurogenesis and some evidence indicates a functional link between olfactory neurogenesis and maternal behavior. Although a simple compound has been found which regulates anogenital licking in the rat, studies identifying the chemical nature of these odors are lacking. Neonatal body odors seem to be particularly salient to human mothers who are able to identify their infant's odors. Recent studies have revealed some neural processing of these cues confirming the importance of mother-young chemical communication in our own species.

  10. Olfactory dysfunction: its early temporal relationship and neural correlates in the pathogenesis of Alzheimer's disease.

    PubMed

    Daulatzai, Mak Adam

    2015-10-01

    We interact with the physical world through our senses, and these aid our behavioral performance and various activities of life. Sensory information is transmitted in neuronal networks, and the brain optimally interprets the external and internal milieu/environment. This paper delineates the framework in which the pathogenesis of memory and cognitive dysfunction is underpinned by sensory olfactory dysfunction. ERC is the gateway for olfactory input to the hippocampus, and there is seamless synchronization between sensory function and hippocampal activity. Transmission of olfactory information to the hippocampus is sequential-it is projected from the olfactory receptors to olfactory bulb to the primary olfactory cortex (comprised the anterior olfactory nucleus, the olfactory tubercle, and the piriform cortex) to the entorhinal cortex (ERC). Through perforant pathway ERC enables olfactory inputs to effectively excite hippocampal neurons. One of the earliest pathological changes in Alzheimer's disease (AD) include the olfactory dysfunction and the atrophy in ERC and hippocampus (rate in ERC is higher than in the hippocampus). Olfactory dysfunction negatively impacts the ERC and the deafferenting of the hippocampus from olfactory inputs upregulates memory decline. Olfactory dysfunction, therefore, is an important and early correlate of AD pathology. A number of factors described here may cause olfactory dysfunction; this may lead to hypoperfusion, hypometabolism, impaired synaptic transmission, and variable atrophy in olfaction-related regions. Improvement in olfactory function, therefore, is an important goal in order to attenuate cognitive neuropathology in aging and AD. This article seeks to provide a comprehensive and balanced overview of olfactory neuropathology in incipient AD, and suggests strategies to enhance olfactory function and ameliorate cognitive decline. PMID:25944089

  11. Kappe neurons, a novel population of olfactory sensory neurons

    NASA Astrophysics Data System (ADS)

    Ahuja, Gaurav; Nia, Shahrzad Bozorg; Zapilko, Veronika; Shiriagin, Vladimir; Kowatschew, Daniel; Oka, Yuichiro; Korsching, Sigrun I.

    2014-02-01

    Perception of olfactory stimuli is mediated by distinct populations of olfactory sensory neurons, each with a characteristic set of morphological as well as functional parameters. Beyond two large populations of ciliated and microvillous neurons, a third population, crypt neurons, has been identified in teleost and cartilaginous fishes. We report here a novel, fourth olfactory sensory neuron population in zebrafish, which we named kappe neurons for their characteristic shape. Kappe neurons are identified by their Go-like immunoreactivity, and show a distinct spatial distribution within the olfactory epithelium, similar to, but significantly different from that of crypt neurons. Furthermore, kappe neurons project to a single identified target glomerulus within the olfactory bulb, mdg5 of the mediodorsal cluster, whereas crypt neurons are known to project exclusively to the mdg2 glomerulus. Kappe neurons are negative for established markers of ciliated, microvillous and crypt neurons, but appear to have microvilli. Kappe neurons constitute the fourth type of olfactory sensory neurons reported in teleost fishes and their existence suggests that encoding of olfactory stimuli may require a higher complexity than hitherto assumed already in the peripheral olfactory system.

  12. Shedding Some Light on Fluorescent Bulbs.

    ERIC Educational Resources Information Center

    Guilbert, Nicholas R.

    1996-01-01

    Explores some of the principles behind the working of fluorescent bulbs using a specially prepared fluorescent bulb with the white inner fluorescent coating applied along only half its length. Discusses the spectrum, the bulb plasma, and light production. (JRH)

  13. Projections from the posterolateral olfactory amygdala to the ventral striatum: neural basis for reinforcing properties of chemical stimuli

    PubMed Central

    Ubeda-Bañon, Isabel; Novejarque, Amparo; Mohedano-Moriano, Alicia; Pro-Sistiaga, Palma; de la Rosa-Prieto, Carlos; Insausti, Ricardo; Martinez-Garcia, Fernando; Lanuza, Enrique; Martinez-Marcos, Alino

    2007-01-01

    Background Vertebrates sense chemical stimuli through the olfactory receptor neurons whose axons project to the main olfactory bulb. The main projections of the olfactory bulb are directed to the olfactory cortex and olfactory amygdala (the anterior and posterolateral cortical amygdalae). The posterolateral cortical amygdaloid nucleus mainly projects to other amygdaloid nuclei; other seemingly minor outputs are directed to the ventral striatum, in particular to the olfactory tubercle and the islands of Calleja. Results Although the olfactory projections have been previously described in the literature, injection of dextran-amines into the rat main olfactory bulb was performed with the aim of delimiting the olfactory tubercle and posterolateral cortical amygdaloid nucleus in our own material. Injection of dextran-amines into the posterolateral cortical amygdaloid nucleus of rats resulted in anterograde labeling in the ventral striatum, in particular in the core of the nucleus accumbens, and in the medial olfactory tubercle including some islands of Calleja and the cell bridges across the ventral pallidum. Injections of Fluoro-Gold into the ventral striatum were performed to allow retrograde confirmation of these projections. Conclusion The present results extend previous descriptions of the posterolateral cortical amygdaloid nucleus efferent projections, which are mainly directed to the core of the nucleus accumbens and the medial olfactory tubercle. Our data indicate that the projection to the core of the nucleus accumbens arises from layer III; the projection to the olfactory tubercle arises from layer II and is much more robust than previously thought. This latter projection is directed to the medial olfactory tubercle including the corresponding islands of Calleja, an area recently described as critical node for the neural circuit of addiction to some stimulant drugs of abuse. PMID:18047654

  14. Functional MRI of the Olfactory System in Conscious Dogs

    PubMed Central

    Jia, Hao; Pustovyy, Oleg M.; Waggoner, Paul; Beyers, Ronald J.; Schumacher, John; Wildey, Chester; Barrett, Jay; Morrison, Edward; Salibi, Nouha; Denney, Thomas S.; Vodyanoy, Vitaly J.; Deshpande, Gopikrishna

    2014-01-01

    We depend upon the olfactory abilities of dogs for critical tasks such as detecting bombs, landmines, other hazardous chemicals and illicit substances. Hence, a mechanistic understanding of the olfactory system in dogs is of great scientific interest. Previous studies explored this aspect at the cellular and behavior levels; however, the cognitive-level neural substrates linking them have never been explored. This is critical given the fact that behavior is driven by filtered sensory representations in higher order cognitive areas rather than the raw odor maps of the olfactory bulb. Since sedated dogs cannot sniff, we investigated this using functional magnetic resonance imaging of conscious dogs. We addressed the technical challenges of head motion using a two pronged strategy of behavioral training to keep dogs' head as still as possible and a single camera optical head motion tracking system to account for residual jerky movements. We built a custom computer-controlled odorant delivery system which was synchronized with image acquisition, allowing the investigation of brain regions activated by odors. The olfactory bulb and piriform lobes were commonly activated in both awake and anesthetized dogs, while the frontal cortex was activated mainly in conscious dogs. Comparison of responses to low and high odor intensity showed differences in either the strength or spatial extent of activation in the olfactory bulb, piriform lobes, cerebellum, and frontal cortex. Our results demonstrate the viability of the proposed method for functional imaging of the olfactory system in conscious dogs. This could potentially open up a new field of research in detector dog technology. PMID:24466054

  15. Plasticity of glomeruli and olfactory-mediated behavior in zebrafish following detergent lesioning of the olfactory epithelium.

    PubMed

    White, E J; Kounelis, S K; Byrd-Jacobs, C A

    2015-01-22

    The zebrafish olfactory system is a valuable model for examining neural regeneration after damage due to the remarkable plasticity of this sensory system and of fish species. We applied detergent to the olfactory organ and examined the effects on both morphology and function of the olfactory system in adult zebrafish. Olfactory organs were treated once with Triton X-100 unilaterally to study glomerular innervation patterns or bilaterally to study odor detection. Fish were allowed to recover for 4-10 days and were compared to untreated control fish. Axonal projections were analyzed using whole mount immunocytochemistry with anti-keyhole limpet hemocyanin, a marker of olfactory axons in teleosts. Chemical lesioning of the olfactory organ with a single dose of Triton X-100 had profound effects on glomerular distribution in the olfactory bulb at 4 days after treatment, with the most significant effects in the medial region of the bulb. Glomeruli had returned by 7 days post-treatment. Analysis of the ability of the fish to detect cocktails of amino acids or bile salts consisted of counting the number of turns the fish made before and after odorant delivery. Control fish turned more after exposure to both odorants. Fish tested 4 and 7 days after chemical lesioning made more turns in response to amino acids but did not respond to bile salts. At 10 days post-lesion, these fish had regained the ability to detect bile salts. Thus, the changes seen in bulbar innervation patterns correlated to odorant-mediated behavior. We show that the adult zebrafish brain has the capacity to recover rapidly from detergent damage of the olfactory epithelium, with both glomerular distribution and odorant-mediated behavior returning in 10 days.

  16. Olfactory cell-based biosensor: a first step towards a neurochip of bioelectronic nose.

    PubMed

    Liu, Qingjun; Cai, Hua; Xu, Ying; Li, Yan; Li, Rong; Wang, Ping

    2006-08-15

    Human olfactory system can distinguish thousands of odors. In order to realize the biomimetic design of electronic nose on the principle of mammalian olfactory system, this article reports an olfactory cell-based biosensor as a real bionic technique for odorants detection. Effective cultures of olfactory receptor neurons and olfactory bulb cells have been achieved on the semiconductor chip. Using light-addressable potentiometric sensor (LAPS) as sensing chip to monitor extracellular potential of the neurons, the response under stimulations of the odorants or neurotransmitters, such as acetic acid and glutamic acid, was tested. The results demonstrate that this kind of hybrid system of LAPS and olfactory neurons, which is sensitive to odorous changes, has great potential and is promising to be used as a novel neurochip of bioelectronic nose for detecting odors.

  17. Effects of Manganese Exposure on Olfactory Functions in Teenagers: A Pilot Study.

    PubMed

    Iannilli, Emilia; Gasparotti, Roberto; Hummel, Thomas; Zoni, Silvia; Benedetti, Chiara; Fedrighi, Chiara; Tang, Cheuk Ying; Van Thriel, Christoph; Lucchini, Roberto G

    2016-01-01

    Long-term exposure to environmental manganese (Mn) affects not only attention and neuromotor functions but also olfactory functions of a pre-adolescent local population who have spent their whole life span in contaminated areas. In order to investigate the effect of such exposure at the level of the central nervous system we set up a pilot fMRI experiment pointing at differences of brain activities between a non-exposed population (nine subjects) and an exposed one (three subjects). We also measured the volume of the olfactory bulb as well as the identification of standard olfactory stimuli. Our results suggest that young subjects exposed to Mn exhibit a reduction of BOLD signal, subjective odor sensitivity and olfactory bulb volume. Moreover a region of interest SPM analysis showed a specifically reduced response of the limbic system in relation to Mn exposure, suggesting an alteration of the brain network dealing with emotional responses. PMID:26765332

  18. Effects of Manganese Exposure on Olfactory Functions in Teenagers: A Pilot Study.

    PubMed

    Iannilli, Emilia; Gasparotti, Roberto; Hummel, Thomas; Zoni, Silvia; Benedetti, Chiara; Fedrighi, Chiara; Tang, Cheuk Ying; Van Thriel, Christoph; Lucchini, Roberto G

    2016-01-01

    Long-term exposure to environmental manganese (Mn) affects not only attention and neuromotor functions but also olfactory functions of a pre-adolescent local population who have spent their whole life span in contaminated areas. In order to investigate the effect of such exposure at the level of the central nervous system we set up a pilot fMRI experiment pointing at differences of brain activities between a non-exposed population (nine subjects) and an exposed one (three subjects). We also measured the volume of the olfactory bulb as well as the identification of standard olfactory stimuli. Our results suggest that young subjects exposed to Mn exhibit a reduction of BOLD signal, subjective odor sensitivity and olfactory bulb volume. Moreover a region of interest SPM analysis showed a specifically reduced response of the limbic system in relation to Mn exposure, suggesting an alteration of the brain network dealing with emotional responses.

  19. Effects of Manganese Exposure on Olfactory Functions in Teenagers: A Pilot Study

    PubMed Central

    Iannilli, Emilia; Gasparotti, Roberto; Hummel, Thomas; Zoni, Silvia; Benedetti, Chiara; Fedrighi, Chiara; Tang, Cheuk Ying; Van Thriel, Christoph; Lucchini, Roberto G.

    2016-01-01

    Long-term exposure to environmental manganese (Mn) affects not only attention and neuromotor functions but also olfactory functions of a pre-adolescent local population who have spent their whole life span in contaminated areas. In order to investigate the effect of such exposure at the level of the central nervous system we set up a pilot fMRI experiment pointing at differences of brain activities between a non-exposed population (nine subjects) and an exposed one (three subjects). We also measured the volume of the olfactory bulb as well as the identification of standard olfactory stimuli. Our results suggest that young subjects exposed to Mn exhibit a reduction of BOLD signal, subjective odor sensitivity and olfactory bulb volume. Moreover a region of interest SPM analysis showed a specifically reduced response of the limbic system in relation to Mn exposure, suggesting an alteration of the brain network dealing with emotional responses. PMID:26765332

  20. A computational framework for temporal sharpening of stimulus input in the olfactory system.

    PubMed

    Zak, Joseph D

    2016-04-01

    The olfactory bulb glomerulus is a dense amalgamation of many unique and interconnected cell types. The mechanisms by which these neurons transform incoming information from the sensory periphery have been extensively studied but often with conflicting findings. A recent study by Carey et al. (J Neurophysiol 113: 3 112-3129, 2015) details the computational framework for parallel modes of temporal refinement of stimulus input to the olfactory system mediated by local neurons within individual glomeruli.

  1. Expression of corticosteroid binding globulin in the rat olfactory system.

    PubMed

    Dölz, Wilfried; Eitner, Annett; Caldwell, Jack D; Jirikowski, Gustav F

    2013-05-01

    Glucocorticoids are known to act on the olfactory system although their mode of action is still unclear since nuclear glucocorticoid receptors are mostly absent in the olfactory mucosa. In this study we used immunocytochemistry, in situ hybridization, and RT-PCR to study the expression and distribution of corticosteroid binding globulin (CBG) in the rat olfactory system. Mucosal goblet cells could be immunostained for CBG. Nasal secretion contained measurable amounts of CBG suggesting that CBG is liberated. CBG immunoreactivity was localized in many of the basal cells of the olfactory mucosa, while mature sensory cells contained CBG only in processes as determined by double immunostaining with the olfactory marker protein OMP. This staining was most pronounced in the vomeronasal organ (VNO). The appearance of CBG in the non-sensory and sensory parts of the VNO and in nerve terminals in the accessory bulb indicated axonal transport. Portions of the periglomerular cells, the mitral cells and the tufted cells were also CBG positive. CBG encoding transcripts were confirmed by RT-PCR in homogenates of the olfactory mucosa and VNO. Olfactory CBG may be significant for uptake, accumulation and transport of glucocorticoids, including aerosolic cortisol.

  2. Extinction reverses olfactory fear-conditioned increases in neuron number and glomerular size.

    PubMed

    Morrison, Filomene G; Dias, Brian G; Ressler, Kerry J

    2015-10-13

    Although much work has investigated the contribution of brain regions such as the amygdala, hippocampus, and prefrontal cortex to the processing of fear learning and memory, fewer studies have examined the role of sensory systems, in particular the olfactory system, in the detection and perception of cues involved in learning and memory. The primary sensory receptive field maps of the olfactory system are exquisitely organized and respond dynamically to cues in the environment, remaining plastic from development through adulthood. We have previously demonstrated that olfactory fear conditioning leads to increased odorant-specific receptor representation in the main olfactory epithelium and in glomeruli within the olfactory bulb. We now demonstrate that olfactory extinction training specific to the conditioned odor stimulus reverses the conditioning-associated freezing behavior and odor learning-induced structural changes in the olfactory epithelium and olfactory bulb in an odorant ligand-specific manner. These data suggest that learning-induced freezing behavior, structural alterations, and enhanced neural sensory representation can be reversed in adult mice following extinction training.

  3. Nasal Administration of Cholera Toxin as a Mucosal Adjuvant Damages the Olfactory System in Mice

    PubMed Central

    Fukuyama, Yoshiko; Okada, Kazunari; Yamaguchi, Masahiro; Kiyono, Hiroshi; Mori, Kensaku; Yuki, Yoshikazu

    2015-01-01

    Cholera toxin (CT) induces severe diarrhea in humans but acts as an adjuvant to enhance immune responses to vaccines when administered orally. Nasally administered CT also acts as an adjuvant, but CT and CT derivatives, including the B subunit of CT (CTB), are taken up from the olfactory epithelium and transported to the olfactory bulbs and therefore may be toxic to the central nervous system. To assess the toxicity, we investigated whether nasally administered CT or CT derivatives impair the olfactory system. In mice, nasal administration of CT, but not CTB or a non-toxic CT derivative, reduced the expression of olfactory marker protein (OMP) in the olfactory epithelium and olfactory bulbs and impaired odor responses, as determined with behavioral tests and optical imaging. Thus, nasally administered CT, like orally administered CT, is toxic and damages the olfactory system in mice. However, CTB and a non-toxic CT derivative, do not damage the olfactory system. The optical imaging we used here will be useful for assessing the safety of nasal vaccines and adjuvants during their development for human use and CT can be used as a positive control in this test. PMID:26422280

  4. Lamp bulb with integral reflector

    DOEpatents

    Levin, Izrail; Shanks, Bruce; Sumner, Thomas L.

    2001-01-01

    An improved electrodeless discharge lamp bulb includes an integral ceramic reflector as a portion of the bulb envelope. The bulb envelope further includes two pieces, a reflector portion or segment is cast quartz ceramic and a light transmissive portion is a clear fused silica. In one embodiment, the cast quartz ceramic segment includes heat sink fins or stubs providing an increased outside surface area to dissipate internal heat. In another embodiment, the quartz ceramic segment includes an outside surface fused to eliminate gas permeation by polishing.

  5. Nitric oxide synthesis in locust olfactory interneurones

    PubMed

    Elphick; Rayne; Riveros-Moreno; Moncada; Shea

    1995-01-01

    The brain of the locust Schistocerca gregaria contains a nitric oxide synthase (NOS) that has similar properties to mammalian neuronal NOS. It catalyses the production of equimolar quantities of nitric oxide (NO) and citrulline from l-arginine in a Ca2+/calmodulin- and NADPH-dependent manner and is inhibited by the Nomega-nitro and Nomega-monomethyl analogues of l-arginine. In Western blots, an antiserum to the 160 kDa rat cerebellar NOS subunit recognises a locust brain protein with a molecular mass of approximately 135 kDa. NOS is located in several parts of the locust brain, including the mushroom bodies, but it is particularly abundant in the olfactory processing centres, the antennal lobes. Here it is present in two groups of local interneurones (a pair and a cluster of about 50) that project into the neuropile of the antennal lobes. The processes of these neurones terminate in numerous glomerulus-like structures where the synapses between primary olfactory receptor neurones and central interneurones are formed. NOS-containing local interneurones have also been identified in the mammalian olfactory bulb, suggesting that NO performs analogous functions in locust and mammalian olfactory systems. As yet, nothing is known about the role of NO in olfaction, but it seems likely that it is involved in the processing of chemosensory input to the brain. The locust antennal lobe may be an ideal 'simple' system in which this aspect of NO function can be examined.

  6. What Is the Real Efficiency of Bulbs?

    ERIC Educational Resources Information Center

    Polacek, Lubos

    2012-01-01

    Bulbs are considered to be very inefficient sources of light. Bulbs give light and heat. As we use them for a long time, especially in winter, a large part of the heat produced by bulbs lowers the power consumption of the heating system. In this paper the problem of the real efficiency of a bulb is solved when both the lighting and heating effects…

  7. Identification of G protein α subunits in the main olfactory system and vomeronasal system of the Japanese Striped snake, Elaphe quadrivirgata.

    PubMed

    Kondoh, Daisuke; Koshi, Katsuo; Ono, Hisaya K; Sasaki, Kuniaki; Nakamuta, Nobuaki; Taniguchi, Kazuyuki

    2013-01-01

    In the olfactory system, G proteins couple to the olfactory receptors, and G proteins expressed in the main olfactory system and vomeronasal system vary according to animal species. In this study, G protein α subunits expressed in the main olfactory system and vomeronasal system of the snake were identified by immunohistochemistry. In the olfactory epithelium, only anti-Gαolf/s antibody labeled the cilia of the receptor cells. In the vomeronasal epithelium, only anti-Gαo antibody labeled the microvilli of the receptor cells. In the accessory olfactory bulb, anti-Gαo antibody stained the whole glomerular layer. These results suggest that the main olfactory system and the vomeronasal system of the snake express Gαolf and Gαo as G proteins coupling to the olfactory receptors, respectively.

  8. Chronic restricted access to food leading to undernutrition affects rat neuroendocrine status and olfactory-driven behaviors.

    PubMed

    Badonnel, Karine; Lacroix, Marie-Christine; Monnerie, Régine; Durieux, Didier; Caillol, Monique; Baly, Christine

    2012-07-01

    Previous studies have demonstrated that olfactory-driven behaviors in rats are influenced by short-term caloric restriction, partly through the modulation of olfactory sensitivity by appetite-modulating hormones or peptides such as insulin and leptin. Here, we addressed the issue of a long-term modulation of their neuroendocrine status by evaluating the effect of chronic food restriction in rats following a limitation of the duration of daily food intake to 2 h (SF) instead of 8 h (LF) on the expression of insulin and leptin system in the olfactory mucosa and bulb and on olfactory behaviors. This restriction resulted in a one-third reduction in the daily food intake and a 25% reduction in the body weight of SF rats when compared to controls, and was accompanied by lower levels of triglycerides, glucose, insulin and leptin in SF rats. Under these conditions, we observed a modulation of olfactory-mediated behaviors regarding food odors. In addition, restriction had a differential effect on the expression of insulin receptors, but not that of leptin receptors, in the olfactory mucosa, whereas no transcriptional change was observed at the upper level of the olfactory bulb. Overall, these data demonstrated that long-term changes in nutritional status modulate olfactory-mediated behaviors. Modulation of insulin system expression in the olfactory mucosa of food restricted rats suggests that this hormone could be part of this process.

  9. Dendritic Organization of Olfactory Inputs to Medial Amygdala Neurons.

    PubMed

    Keshavarzi, Sepideh; Power, John M; Albers, Eva H H; Sullivan, Robert K S; Sah, Pankaj

    2015-09-23

    The medial amygdala (MeA) is a central hub in the olfactory neural network. It receives vomeronasal information directly from the accessory olfactory bulb (AOB) and main olfactory information largely via odor-processing regions such as the olfactory cortical amygdala (CoA). How these inputs are processed by MeA neurons is poorly understood. Using the GAD67-GFP mouse, we show that MeA principal neurons receive convergent AOB and CoA inputs. Somatically recorded AOB synaptic inputs had slower kinetics than CoA inputs, suggesting that they are electrotonically more distant. Field potential recording, pharmacological manipulation, and Ca(2+) imaging revealed that AOB synapses are confined to distal dendrites and segregated from the proximally located CoA synapses. Moreover, unsynchronized AOB inputs had significantly broader temporal summation that was dependent on the activation of NMDA receptors. These findings show that MeA principal neurons process main and accessory olfactory inputs differentially in distinct dendritic compartments. Significance statement: In most vertebrates, olfactory cues are processed by two largely segregated neural pathways, the main and accessory olfactory systems, which are specialized to detect odors and nonvolatile chemosignals, respectively. Information from these two pathways ultimately converges at higher brain regions, one of the major hubs being the medial amygdala. Little is known about how olfactory inputs are processed by medial amygdala neurons. This study shows that individual principal neurons in this region receive input from both pathways and that these synapses are spatially segregated on their dendritic tree. We provide evidence suggesting that this dendritic segregation leads to distinct input integration and impact on neuronal output; hence, dendritic mechanisms control olfactory processing in the amygdala. PMID:26400933

  10. The olfactory system as a puzzle: playing with its pieces.

    PubMed

    Díaz, D; Gómez, C; Muñoz-Castañeda, R; Baltanás, F; Alonso, J R; Weruaga, E

    2013-09-01

    The mammalian olfactory bulb (OB) has all the features of a whole mammalian brain but in a more reduced space: neuronal lamination, sensory inputs, afferences, or efferences to other centers of the central nervous system, or a contribution of new neural elements. Therefore, it is widely considered as "a brain inside the brain." Although this rostral region has the same origin and general layering as the other cerebral cortices, some distinctive features make it very profitable in experimentation in neurobiology: the sensory inputs are driven directly on its surface, the main output can be accessed anatomically, and new elements appear in it throughout adult life. These three morphological characteristics have been manipulated to analyze further the response of the whole OB. The present review offers a general outlook into the consequences of such experimentation in the anatomy, connectivity and neurochemistry of the OB after (a) sensory deprivation, mainly by naris occlusion; (b) olfactory deinnervation by means of olfactory epithelium damage, olfactory nerve interruption, or even olfactory tract disruption; (c) the removal of the principal neurons of the OB; and (d) management of the arrival of newborn interneurons from the rostral migratory stream. These experiments were performed using surgical or chemical methods, but also by means of the analysis of genetic models, some of whose olfactory components are missing, colorless or mismatching within the wild-type scenario of odor processing.

  11. [Blockade of the pheromonal effects in rat by central deafferentation of the accessory olfactory system].

    PubMed

    Sánchez-Criado, J E

    1979-06-01

    Female rats reared without sex odours from male rats have a five day stral cycle. With exposure to male odour the estral cycle is shortened from five to four days. This pheromonal effect is blocked on deafferenting the vomeronasal system by electrolytically damaging both accessory olfactory bulbs.

  12. alpha-Synucleinopathy in the human olfactory system in Parkinson's disease: involvement of calcium-binding protein- and substance P-positive cells.

    PubMed

    Ubeda-Bañon, Isabel; Saiz-Sanchez, Daniel; de la Rosa-Prieto, Carlos; Argandoña-Palacios, Lucia; Garcia-Muñozguren, Susana; Martinez-Marcos, Alino

    2010-06-01

    Hyposmia is an early symptom of idiopathic Parkinson's disease but the pathological bases of such dysfunction are largely unknown. The distribution of alpha-synuclein, which forms Lewy bodies and Lewy neurites, and the types of neurons (based on their neurotransmitters) affected by alpha-synucleinopathy were investigated in the olfactory system in Parkinson's disease. Immunohistochemical distribution of alpha-synuclein and its co-localization with tyrosine hydroxylase, somatostatin, calbindin, calretinin, parvalbumin and substance P in the olfactory bulb, anterior olfactory nucleus, olfactory tubercle and piriform, periamygdaloid and rostral entorhinal cortices of idiopathic Parkinson's disease cases (n = 11) and age-matched controls (n = 11) were investigated. Lewy bodies and Lewy neurites were present in the olfactory bulb, particularly in mitral cells and in the inner plexiform layer. alpha-synuclein was particularly abundant in the different divisions of the anterior olfactory nucleus (bulbar, intrapeduncular, retrobulbar and cortical). In contrast, Lewy bodies and Lewy neurites were less abundant in the olfactory tubercle and olfactory cortices. In the olfactory bulb, anterior olfactory nucleus and olfactory cortices, cells affected by alpha-synucleinopathy rarely co-localized tyrosine hydroxylase or somatostatin, but they frequently co-localized calbindin, calretinin, parvalbumin and substance P. The present data provide evidence that alpha-synucleinopathy affects neurons along the olfactory pathway. Dopamine- and somatostatin-positive cells are rarely affected; whereas the cell types most vulnerable to neurodegeneration include glutamate- (mitral cells), calcium-binding protein- and substance P-positive cells. These results provide data on the distribution and cell types involved by alpha-synucleinopathy in the human olfactory system during Parkinson disease that may be useful for future clinical investigation.

  13. Proboscis lateralis with ipsilateral sinonasal and olfactory pathway aplasia.

    PubMed

    Vaid, Sanjay; Shah, Darshan; Rawat, Sudarshan; Shukla, Rahul

    2010-02-01

    Proboscis lateralis is a rare craniofacial malformation characterized by absence of nasal cavity on one side with a trunk-like nasal appendage protruding from superomedial portion of the ipsilateral orbit. High-resolution computed tomography and magnetic resonance imaging are extremely useful in evaluating this congenital condition and the wide spectrum of associated anomalies occurring in the surrounding anatomical regions and brain. We present a case of proboscis lateralis in a 2-year-old girl with associated ipsilateral sinonasal aplasia, orbital cyst, absent olfactory bulb and olfactory tract. Absence of ipsilateral olfactory pathway in this rare disorder has been documented on high-resolution computed tomography and magnetic resonance imaging by us for the first time in English medical literature. PMID:20152374

  14. The endocannabinoid system controls food intake via olfactory processes.

    PubMed

    Soria-Gómez, Edgar; Bellocchio, Luigi; Reguero, Leire; Lepousez, Gabriel; Martin, Claire; Bendahmane, Mounir; Ruehle, Sabine; Remmers, Floor; Desprez, Tifany; Matias, Isabelle; Wiesner, Theresa; Cannich, Astrid; Nissant, Antoine; Wadleigh, Aya; Pape, Hans-Christian; Chiarlone, Anna Paola; Quarta, Carmelo; Verrier, Daniéle; Vincent, Peggy; Massa, Federico; Lutz, Beat; Guzmán, Manuel; Gurden, Hirac; Ferreira, Guillaume; Lledo, Pierre-Marie; Grandes, Pedro; Marsicano, Giovanni

    2014-03-01

    Hunger arouses sensory perception, eventually leading to an increase in food intake, but the underlying mechanisms remain poorly understood. We found that cannabinoid type-1 (CB1) receptors promote food intake in fasted mice by increasing odor detection. CB1 receptors were abundantly expressed on axon terminals of centrifugal cortical glutamatergic neurons that project to inhibitory granule cells of the main olfactory bulb (MOB). Local pharmacological and genetic manipulations revealed that endocannabinoids and exogenous cannabinoids increased odor detection and food intake in fasted mice by decreasing excitatory drive from olfactory cortex areas to the MOB. Consistently, cannabinoid agonists dampened in vivo optogenetically stimulated excitatory transmission in the same circuit. Our data indicate that cortical feedback projections to the MOB crucially regulate food intake via CB1 receptor signaling, linking the feeling of hunger to stronger odor processing. Thus, CB1 receptor-dependent control of cortical feedback projections in olfactory circuits couples internal states to perception and behavior. PMID:24509429

  15. Olfactory receptor for prostaglandin F2α mediates male fish courtship behavior.

    PubMed

    Yabuki, Yoichi; Koide, Tetsuya; Miyasaka, Nobuhiko; Wakisaka, Noriko; Masuda, Miwa; Ohkura, Masamichi; Nakai, Junichi; Tsuge, Kyoshiro; Tsuchiya, Soken; Sugimoto, Yukihiko; Yoshihara, Yoshihiro

    2016-07-01

    Pheromones play vital roles for survival and reproduction in various organisms. In many fishes, prostaglandin F2α acts not only as a female reproductive hormone, facilitating ovulation and spawning, but also as a sex pheromone inducing male reproductive behaviors. Here, we unravel the molecular and neural circuit mechanisms underlying the pheromonal action of prostaglandin F2α in zebrafish. Prostaglandin F2α specifically activates two olfactory receptors with different sensitivities and expression in distinct populations of ciliated olfactory sensory neurons. Pheromone information is then transmitted to two ventromedial glomeruli in the olfactory bulb and further to four regions in higher olfactory centers. Mutant male zebrafish deficient in the high-affinity receptor exhibit loss of attractive response to prostaglandin F2α and impairment of courtship behaviors toward female fish. These findings demonstrate the functional significance and activation of selective neural circuitry for the sex pheromone prostaglandin F2α and its cognate olfactory receptor in fish reproductive behavior. PMID:27239939

  16. Phylogenic studies on the olfactory system in vertebrates.

    PubMed

    Taniguchi, Kazuyuki; Taniguchi, Kazumi

    2014-06-01

    The olfactory receptor organs and their primary centers are classified into several types. The receptor organs are divided into fish-type olfactory epithelium (OE), mammal-type OE, middle chamber epithelium (MCE), lower chamber epithelium (LCE), recess epithelium, septal olfactory organ of Masera (SO), mammal-type vomeronasal organ (VNO) and snake-type VNO. The fish-type OE is observed in flatfish and lungfish, while the mammal-type OE is observed in amphibians, reptiles, birds and mammals. The MCE and LCE are unique to Xenopus and turtles, respectively. The recess epithelium is unique to lungfish. The SO is observed only in mammals. The mammal-type VNO is widely observed in amphibians, lizards and mammals, while the snake-type VNO is unique to snakes. The VNO itself is absent in turtles and birds. The mammal-type OE, MCE, LCE and recess epithelium seem to be descendants of the fish-type OE that is derived from the putative primitive OE. The VNO may be derived from the recess epithelium or fish-type OE and differentiate into the mammal-type VNO and snake-type VNO. The primary olfactory centers are divided into mammal-type main olfactory bulbs (MOB), fish-type MOB and mammal-type accessory olfactory bulbs (AOB). The mammal-type MOB first appears in amphibians and succeeds to reptiles, birds and mammals. The fish-type MOB, which is unique to fish, may be the ancestor of the mammal-type MOB. The mammal-type AOB is observed in amphibians, lizards, snakes and mammals and may be the remnant of the fish-type MOB.

  17. Phylogenic Studies on the Olfactory System in Vertebrates

    PubMed Central

    TANIGUCHI, Kazuyuki; TANIGUCHI, Kazumi

    2014-01-01

    ABSTRACT The olfactory receptor organs and their primary centers are classified into several types. The receptor organs are divided into fish-type olfactory epithelium (OE), mammal-type OE, middle chamber epithelium (MCE), lower chamber epithelium (LCE), recess epithelium, septal olfactory organ of Masera (SO), mammal-type vomeronasal organ (VNO) and snake-type VNO. The fish-type OE is observed in flatfish and lungfish, while the mammal-type OE is observed in amphibians, reptiles, birds and mammals. The MCE and LCE are unique to Xenopus and turtles, respectively. The recess epithelium is unique to lungfish. The SO is observed only in mammals. The mammal-type VNO is widely observed in amphibians, lizards and mammals, while the snake-type VNO is unique to snakes. The VNO itself is absent in turtles and birds. The mammal-type OE, MCE, LCE and recess epithelium seem to be descendants of the fish-type OE that is derived from the putative primitive OE. The VNO may be derived from the recess epithelium or fish-type OE and differentiate into the mammal-type VNO and snake-type VNO. The primary olfactory centers are divided into mammal-type main olfactory bulbs (MOB), fish-type MOB and mammal-type accessory olfactory bulbs (AOB). The mammal-type MOB first appears in amphibians and succeeds to reptiles, birds and mammals. The fish-type MOB, which is unique to fish, may be the ancestor of the mammal-type MOB. The mammal-type AOB is observed in amphibians, lizards, snakes and mammals and may be the remnant of the fish-type MOB. PMID:24531771

  18. Olfactory Receptor Patterning in a Higher Primate

    PubMed Central

    Horowitz, Lisa F.; Saraiva, Luis R.; Kuang, Donghui; Yoon, Kyoung-hye

    2014-01-01

    The mammalian olfactory system detects a plethora of environmental chemicals that are perceived as odors or stimulate instinctive behaviors. Studies using odorant receptor (OR) genes have provided insight into the molecular and organizational strategies underlying olfaction in mice. One important unanswered question, however, is whether these strategies are conserved in primates. To explore this question, we examined the macaque, a higher primate phylogenetically close to humans. Here we report that the organization of sensory inputs in the macaque nose resembles that in mouse in some respects, but not others. As in mouse, neurons with different ORs are interspersed in the macaque nose, and there are spatial zones that differ in their complement of ORs and extend axons to different domains in the olfactory bulb of the brain. However, whereas the mouse has multiple discrete band-like zones, the macaque appears to have only two broad zones. It is unclear whether the organization of OR inputs in a rodent/primate common ancestor degenerated in primates or, alternatively became more sophisticated in rodents. The mouse nose has an additional small family of chemosensory receptors, called trace amine-associated receptors (TAARs), which may detect social cues. Here we find that TAARs are also expressed in the macaque nose, suggesting that TAARs may also play a role in human olfactory perception. We further find that one human TAAR responds to rotten fish, suggesting a possible role as a sentinel to discourage ingestion of food harboring pathogenic microorganisms. PMID:25209267

  19. CD36 is involved in oleic acid detection by the murine olfactory system.

    PubMed

    Oberland, Sonja; Ackels, Tobias; Gaab, Stefanie; Pelz, Thomas; Spehr, Jennifer; Spehr, Marc; Neuhaus, Eva M

    2015-01-01

    Olfactory signals influence food intake in a variety of species. To maximize the chances of finding a source of calories, an animal's preference for fatty foods and triglycerides already becomes apparent during olfactory food search behavior. However, the molecular identity of both receptors and ligands mediating olfactory-dependent fatty acid recognition are, so far, undescribed. We here describe that a subset of olfactory sensory neurons expresses the fatty acid receptor CD36 and demonstrate a receptor-like localization of CD36 in olfactory cilia by STED microscopy. CD36-positive olfactory neurons share olfaction-specific transduction elements and project to numerous glomeruli in the ventral olfactory bulb. In accordance with the described roles of CD36 as fatty acid receptor or co-receptor in other sensory systems, the number of olfactory neurons responding to oleic acid, a major milk component, in Ca(2+) imaging experiments is drastically reduced in young CD36 knock-out mice. Strikingly, we also observe marked age-dependent changes in CD36 localization, which is prominently present in the ciliary compartment only during the suckling period. Our results support the involvement of CD36 in fatty acid detection by the mammalian olfactory system. PMID:26441537

  20. Nonoccupational environmental exposure to manganese is linked to deficits in peripheral and central olfactory function.

    PubMed

    Guarneros, Marco; Ortiz-Romo, Nahum; Alcaraz-Zubeldia, Mireya; Drucker-Colín, René; Hudson, Robyn

    2013-11-01

    Manganese is of growing concern as a toxic air pollutant. It is readily transported from the olfactory epithelium to the olfactory bulb, and unlike other metals, it is transported transynaptically to structures deep within the brain. However, little is known regarding the possible effect of nonoccupational exposure to manganese on olfactory function. Using the Sniffin' Sticks test battery, we compared the olfactory performance of subjects from a manganese mining district living <1 km from a manganese processing plant, with nonexposed subjects living 50 km from the closest source of exposure (N = 30/group). Groups were matched for age, sex, and schooling, and none had ever worked in mining-related activities. Concentrations of manganese in hair were measured as a biomarker of exposure; exposed subjects had significantly higher concentrations than nonexposed subjects. They were also significantly outperformed by the nonexposed subjects on all olfactory measures (threshold, discrimination, and identification), indicating adverse effects of manganese exposure on a range of olfactory functions, including those involving higher order cognitive processes. This contrasts with previous findings showing adverse peripheral but not central effects on olfactory function of big city air pollution, which mostly consists of toxicants known to affect the olfactory epithelium but with lower transynaptic transport capacity compared with manganese. We conclude that nonoccupational exposure to airborne manganese is associated with decrements in both peripheral and central olfactory function. PMID:24097266

  1. A direct anterior cingulate pathway to the primate primary olfactory cortex may control attention to olfaction

    PubMed Central

    García-Cabezas, Miguel Á.; Barbas, Helen

    2016-01-01

    Behavioral and functional studies in humans suggest that attention plays a key role in activating the primary olfactory cortex through an unknown circuit mechanism. We report that a novel pathway from the anterior cingulate cortex, an area which has a key role in attention, projects directly to the primary olfactory cortex in rhesus monkeys, innervating mostly the anterior olfactory nucleus. Axons from the anterior cingulate cortex formed synapses mostly with spines of putative excitatory pyramidal neurons and with a small proportion of a neurochemical class of inhibitory neurons that are thought to have disinhibitory effect on excitatory neurons. This novel pathway from the anterior cingulate is poised to exert a powerful excitatory effect on the anterior olfactory nucleus, which is a critical hub for odorant processing via extensive bilateral connections with primary olfactory cortices and the olfactory bulb. Acting on the anterior olfactory nucleus, the anterior cingulate may activate the entire primary olfactory cortex to mediate the process of rapid attention to olfactory stimuli. PMID:23797208

  2. Beta and gamma oscillatory activities associated with olfactory memory tasks: different rhythms for different functional networks?

    PubMed Central

    Martin, Claire; Ravel, Nadine

    2014-01-01

    Olfactory processing in behaving animals, even at early stages, is inextricable from top down influences associated with odor perception. The anatomy of the olfactory network (olfactory bulb, piriform, and entorhinal cortices) and its unique direct access to the limbic system makes it particularly attractive to study how sensory processing could be modulated by learning and memory. Moreover, olfactory structures have been early reported to exhibit oscillatory population activities easy to capture through local field potential recordings. An attractive hypothesis is that neuronal oscillations would serve to “bind” distant structures to reach a unified and coherent perception. In relation to this hypothesis, we will assess the functional relevance of different types of oscillatory activity observed in the olfactory system of behaving animals. This review will focus primarily on two types of oscillatory activities: beta (15–40 Hz) and gamma (60–100 Hz). While gamma oscillations are dominant in the olfactory system in the absence of odorant, both beta and gamma rhythms have been reported to be modulated depending on the nature of the olfactory task. Studies from the authors of the present review and other groups brought evidence for a link between these oscillations and behavioral changes induced by olfactory learning. However, differences in studies led to divergent interpretations concerning the respective role of these oscillations in olfactory processing. Based on a critical reexamination of those data, we propose hypotheses on the functional involvement of beta and gamma oscillations for odor perception and memory. PMID:25002840

  3. CD36 is involved in oleic acid detection by the murine olfactory system

    PubMed Central

    Oberland, Sonja; Ackels, Tobias; Gaab, Stefanie; Pelz, Thomas; Spehr, Jennifer; Spehr, Marc; Neuhaus, Eva M.

    2015-01-01

    Olfactory signals influence food intake in a variety of species. To maximize the chances of finding a source of calories, an animal’s preference for fatty foods and triglycerides already becomes apparent during olfactory food search behavior. However, the molecular identity of both receptors and ligands mediating olfactory-dependent fatty acid recognition are, so far, undescribed. We here describe that a subset of olfactory sensory neurons expresses the fatty acid receptor CD36 and demonstrate a receptor-like localization of CD36 in olfactory cilia by STED microscopy. CD36-positive olfactory neurons share olfaction-specific transduction elements and project to numerous glomeruli in the ventral olfactory bulb. In accordance with the described roles of CD36 as fatty acid receptor or co-receptor in other sensory systems, the number of olfactory neurons responding to oleic acid, a major milk component, in Ca2+ imaging experiments is drastically reduced in young CD36 knock-out mice. Strikingly, we also observe marked age-dependent changes in CD36 localization, which is prominently present in the ciliary compartment only during the suckling period. Our results support the involvement of CD36 in fatty acid detection by the mammalian olfactory system. PMID:26441537

  4. The loss of scents: do defects in olfactory sensory neuron development underlie human disease?

    PubMed

    Whitlock, Kathleen E

    2015-06-01

    The olfactory system is a fascinating and beguiling sensory system: olfactory sensory neurons detect odors underlying behaviors essential for mate choice, food selection, and escape from predators, among others. These sensory neurons are unique in that they have dendrites contacting the outside world, yet their first synapse lies in the central nervous system. The information entering the central nervous system is used to create odor memories that play a profound role in recognition of individuals, places, and appropriate foods. Here, the structure of the olfactory epithelium is given as an overview to discuss the origin of the olfactory placode, the plasticity of the olfactory sensory neurons, and finally the origins of the gonadotropin-releasing hormone neuroendocrine cells. For the purposes of this review, the development of the peripheral sensory system will be analyzed, incorporating recently published studies highlighting the potential novelties in development mechanisms. Specifically, an emerging model where the olfactory epithelium and olfactory bulb develop simultaneously from a continuous neurectoderm patterned at the end of gastrulation, and the multiple origins of the gonadotropin-releasing hormone neuroendocrine cells associated with the olfactory sensory system development will be presented. Advances in the understanding of the basic mechanisms underlying olfactory sensory system development allows for a more thorough understanding of the potential causes of human disease.

  5. Development of the olfactory pathways in platypus and echidna.

    PubMed

    Ashwell, Ken W S

    2012-01-01

    The two groups of living monotremes (platypus and echidnas) have remarkably different olfactory structures in the adult. The layers of the main olfactory bulb of the short-beaked echidna are extensively folded, whereas those of the platypus are not. Similarly, the surface area of the piriform cortex of the echidna is large and its lamination complex, whereas in the platypus it is small and simple. It has been argued that the modern echidnas are derived from a platypus-like ancestor, in which case the extensive olfactory specializations of the modern echidnas would have developed relatively recently in monotreme evolution. In this study, the development of the constituent structures of the olfactory pathway was studied in sectioned platypus and echidna embryos and post-hatchlings at the Museum für Naturkunde, Berlin, Germany. The aim was to determine whether the olfactory structures follow a similar maturational path in the two monotremes during embryonic and early post-hatching ages or whether they show very different developmental paths from the outset. The findings indicate that anatomical differences in the central olfactory system between the short-beaked echidna and the platypus begin to develop immediately before hatching, although details of differences in nasal cavity architecture emerge progressively during late post-hatching life. These findings are most consistent with the proposition that the two modern monotreme lineages have followed independent evolutionary paths from a less olfaction-specialized ancestor. The monotreme olfactory pathway does not appear to be sufficiently structurally mature at birth to allow olfaction-mediated behaviour, because central components of both the main and accessory olfactory system have not differentiated at the time of hatching. PMID:22156550

  6. No-Light Light Bulbs

    ERIC Educational Resources Information Center

    Modern Schools, 1976

    1976-01-01

    A thumbnail sketch of some of the light bulbs manufactured for a purpose other than seeing. These "dark" lamps perform varied tasks including keeping food fresh, detecting and preventing disease, spurring plant growth, heating, and copying printed material. (Author/MLF)

  7. Cytological organization of the alpha component of the anterior olfactory nucleus and olfactory limbus

    PubMed Central

    Larriva-Sahd, Jorge

    2012-01-01

    This study describes the microscopic organization of a wedge-shaped area at the intersection of the main (MOB) and accessory olfactory bulbs (AOBs), or olfactory limbus (OL), and an additional component of the anterior olfactory nucleus or alpha AON that lies underneath of the AOB. The OL consists of a modified bulbar cortex bounded anteriorly by the MOB and posteriorly by the AOB. In Nissl-stained specimens the OL differs from the MOB by a progressive, antero-posterior decrease in thickness or absence of the external plexiform, mitral/tufted cell, and granule cell layers. On cytoarchitectual grounds the OL is divided from rostral to caudal into three distinct components: a stripe of glomerular-free cortex or preolfactory area (PA), a second or necklace glomerular area, and a wedge-shaped or interstitial area (INA) crowned by the so-called modified glomeruli that appear to belong to the anterior AOB. The strategic location and interactions with the main and AOBs, together with the previously noted functional and connectional evidence, suggest that the OL may be related to both sensory modalities. The alpha component of the anterior olfactory nucleus, a slender cellular cluster (i.e., 650 × 150 μm) paralleling the base of the AOB, contains two neuron types: a pyramidal-like neuron and an interneuron. Dendrites of pyramidal-like cells (P-L) organize into a single bundle that ascends avoiding the AOB to resolve in a trigone bounded by the edge of the OL, the AOB and the dorsal part of the anterior olfactory nucleus. Utrastructurally, the neuropil of the alpha component contains three types of synaptic terminals; one of them immunoreactive to the enzyme glutamate decarboxylase, isoform 67. PMID:22754506

  8. Bulbocortical interplay in olfactory information processing via synchronous oscillations.

    PubMed

    Fukai, T

    1996-04-01

    Emergence of synchronous oscillatory activity is an inherent feature of the olfactory systems of insects, mollusks and mammals. A class of simple computational models of the mammalian olfactory system consisting of olfactory bulb and olfactory cortex is constructed to explore possible roles of the related neural circuitry in olfactory information processing via synchronous oscillations. In the models, the bulbar neural circuitry is represented by a chain of oscillators and that of cortex is analogous to an associative memory network with horizontal synaptic connections. The models incorporate the backprojection from cortical units to the bulbar oscillators in particular ways. They exhibit rapid and robust synchronous oscillations in the presence of odorant stimuli, while they show either nonoscillatory states or propagating waves in the absence of stimuli, depending on the values of model parameters. In both models, the backprojection is shown to enhance the establishment of large-scale synchrony. The results suggest that the modulation of neural activity through centrifugal inputs may play an important role at the early stage of cortical information processing.

  9. Functional Rehabilitation of Cadmium-Induced Neurotoxicity Despite Persistent Peripheral Pathophysiology in the Olfactory System

    PubMed Central

    Czarnecki, Lindsey A.; Moberly, Andrew H.; Turkel, Daniel J.; Rubinstein, Tom; Pottackal, Joseph; Rosenthal, Michelle C.; McCandlish, Elizabeth F. K.; Buckley, Brian; McGann, John P.

    2012-01-01

    Intranasal exposure to the heavy metal cadmium has been linked to olfactory dysfunction and neurotoxicity. Here, we combine optical imaging of in vivo neurophysiology, genetically defined anatomical tract tracing, mass spectrometry, and behavioral psychophysical methods to evaluate the persistent harmful effects of acute intranasal exposure to cadmium in a mouse model and to investigate the functional consequences of sensory rehabilitation training. We find that an acute intranasal instillation of cadmium chloride leads to an accumulation of cadmium in the brain's olfactory bulb that persists for at least 4 weeks. This is accompanied by persistent severe pathophysiology of the olfactory nerve, a gradual reduction in axonal projections from the olfactory epithelium, and complete impairment on an olfactory detection task. Remarkably, 2 weeks of odorant-guided operant conditioning training proved sufficient to restore olfactory detection performance to control levels in cadmium-exposed mice. Optical imaging from rehabilitated mice showed that this training did not cause any detectable restoration of olfactory nerve function, suggesting that the recovery of function was mediated by central neuroplasticity in which the brain learned to interpret the degraded sensory input. These data demonstrate that sensory learning can mask even severe damage from neurotoxicants and suggest that explicit sensory training may be useful in rehabilitation of olfactory dysfunction. PMID:22287023

  10. The olfactory nerve: a shortcut for influenza and other viral diseases into the central nervous system.

    PubMed

    van Riel, Debby; Verdijk, Rob; Kuiken, Thijs

    2015-01-01

    The olfactory nerve consists mainly of olfactory receptor neurons and directly connects the nasal cavity with the central nervous system (CNS). Each olfactory receptor neuron projects a dendrite into the nasal cavity on the apical side, and on the basal side extends its axon through the cribriform plate into the olfactory bulb of the brain. Viruses that can use the olfactory nerve as a shortcut into the CNS include influenza A virus, herpesviruses, poliovirus, paramyxoviruses, vesicular stomatitis virus, rabies virus, parainfluenza virus, adenoviruses, Japanese encephalitis virus, West Nile virus, chikungunya virus, La Crosse virus, mouse hepatitis virus, and bunyaviruses. However, mechanisms of transport via the olfactory nerve and subsequent spread through the CNS are poorly understood. Proposed mechanisms are either infection of olfactory receptor neurons themselves or diffusion through channels formed by olfactory ensheathing cells. Subsequent virus spread through the CNS could occur by multiple mechanisms, including trans-synaptic transport and microfusion. Viral infection of the CNS can lead to damage from infection of nerve cells per se, from the immune response, or from a combination of both. Clinical consequences range from nervous dysfunction in the absence of histopathological changes to severe meningoencephalitis and neurodegenerative disease.

  11. A novel neural substrate for the transformation of olfactory inputs into motor output.

    PubMed

    Derjean, Dominique; Moussaddy, Aimen; Atallah, Elias; St-Pierre, Melissa; Auclair, François; Chang, Steven; Ren, Xiang; Zielinski, Barbara; Dubuc, Réjean

    2010-01-01

    It is widely recognized that animals respond to odors by generating or modulating specific motor behaviors. These reactions are important for daily activities, reproduction, and survival. In the sea lamprey, mating occurs after ovulated females are attracted to spawning sites by male sex pheromones. The ubiquity and reliability of olfactory-motor behavioral responses in vertebrates suggest tight coupling between the olfactory system and brain areas controlling movements. However, the circuitry and the underlying cellular neural mechanisms remain largely unknown. Using lamprey brain preparations, and electrophysiology, calcium imaging, and tract tracing experiments, we describe the neural substrate responsible for transforming an olfactory input into a locomotor output. We found that olfactory stimulation with naturally occurring odors and pheromones induced large excitatory responses in reticulospinal cells, the command neurons for locomotion. We have also identified the anatomy and physiology of this circuit. The olfactory input was relayed in the medial part of the olfactory bulb, in the posterior tuberculum, in the mesencephalic locomotor region, to finally reach reticulospinal cells in the hindbrain. Activation of this olfactory-motor pathway generated rhythmic ventral root discharges and swimming movements. Our study bridges the gap between behavior and cellular neural mechanisms in vertebrates, identifying a specific subsystem within the CNS, dedicated to producing motor responses to olfactory inputs.

  12. Normal jugular bulb oxygen saturation

    PubMed Central

    Chieregato, A; Calzolari, F; Trasforini, G; Targa, L; Latronico, N

    2003-01-01

    Background: Normal values of the jugular bulb oxygen saturation were obtained in 1942 and in 1963. Correct catheter positioning was not confirmed radiologically. Objectives: To replicate the measurements during angiographic catheterisation of the jugular bulb. Methods: Oxygen saturation in the jugular bulb (SjO2), inferior petrosal sinus (SipsO2), and internal jugular vein was bilaterally measured in 12 patients with Cushing's syndrome undergoing selective bilateral catheterisation of the inferior petrosal sinus. In addition, data from the two old series were reanalysed for comparison. Results: SjO2 values (44.7%) were significantly lower than in the two old series, particularly concerning the normal lower limit (54.6% and 55.0% respectively). Comparative analysis suggests that contamination with the extracerebral blood of the facial veins and inferior petrosal sinuses was responsible for falsely high SjO2 values in the two old series. Conclusions: The normal lower SjO2 limit is lower than previously recognised. This may have practical implications for treating severe head trauma patients. PMID:12754351

  13. Coding and transformations in the olfactory system.

    PubMed

    Uchida, Naoshige; Poo, Cindy; Haddad, Rafi

    2014-01-01

    How is sensory information represented in the brain? A long-standing debate in neural coding is whether and how timing of spikes conveys information to downstream neurons. Although we know that neurons in the olfactory bulb (OB) exhibit rich temporal dynamics, the functional relevance of temporal coding remains hotly debated. Recent recording experiments in awake behaving animals have elucidated highly organized temporal structures of activity in the OB. In addition, the analysis of neural circuits in the piriform cortex (PC) demonstrated the importance of not only OB afferent inputs but also intrinsic PC neural circuits in shaping odor responses. Furthermore, new experiments involving stimulation of the OB with specific temporal patterns allowed for testing the relevance of temporal codes. Together, these studies suggest that the relative timing of neuronal activity in the OB conveys odor information and that neural circuits in the PC possess various mechanisms to decode temporal patterns of OB input.

  14. Evidence for a Notch1-mediated transition during olfactory ensheathing cell development.

    PubMed

    Miller, Sophie R; Perera, Surangi N; Benito, Cristina; Stott, Simon R W; Baker, Clare V H

    2016-09-01

    Olfactory ensheathing cells (OECs) are a unique glial population found in both the peripheral and central nervous system: they ensheath bundles of unmyelinated olfactory axons from their peripheral origin in the olfactory epithelium to their central synaptic targets in the glomerular layer of the olfactory bulb. Like all other peripheral glia (Schwann cells, satellite glia, enteric glia), OECs are derived from the embryonic neural crest. However, in contrast to Schwann cells, whose development has been extensively characterised, relatively little is known about their normal development in vivo. In the Schwann cell lineage, the transition from multipotent Schwann cell precursor to immature Schwann cell is promoted by canonical Notch signalling. Here, in situ hybridisation and immunohistochemistry data from chicken, mouse and human embryos are presented that suggest a canonical Notch-mediated transition also occurs during OEC development. PMID:27271278

  15. Induction of an Olfactory Memory by the Activation of a Metabotropic Glutamate Receptor

    NASA Astrophysics Data System (ADS)

    Kaba, Hideto; Hayashi, Yasunori; Higuchi, Takashi; Nakanishi, Shigetada

    1994-07-01

    Female mice form an olfactory memory of male pheromones at mating; exposure to the pheromones of a strange male after that mating will block pregnancy. The formation of this memory is mediated by the accessory olfactory system, in which an increase in norepinephrine after mating reduces inhibitory transmission of γ-aminobutyric acid from the granule cells to the mitral cells. This study shows that the activation of mGluR2, a metabotropic glutamate receptor that suppresses the γ-aminobutyric acid inhibition of the mitral cells, permits the formation of a specific olfactory memory without the occurrence of mating by infusion of mGluR2 agonists into the female's accessory olfactory bulb. This memory faithfully reflects the memory formed at mating.

  16. Olfactory receptor and neural pathway responsible for highly selective sensing of musk odors.

    PubMed

    Shirasu, Mika; Yoshikawa, Keiichi; Takai, Yoshiki; Nakashima, Ai; Takeuchi, Haruki; Sakano, Hitoshi; Touhara, Kazushige

    2014-01-01

    Musk odorants are used widely in cosmetic industries because of their fascinating animalic scent. However, how this aroma is perceived in the mammalian olfactory system remains a great mystery. Here, we show that muscone, one musk odor secreted by various animals from stink glands, activates a few glomeruli clustered in a neuroanatomically unique anteromedial olfactory bulb. The muscone-responsive glomeruli are highly specific to macrocyclic ketones; interestingly, other synthetic musk odorants with nitro or polycyclic moieties or ester bonds activate distinct but nearby glomeruli. Anterodorsal bulbar lesions cause muscone anosmia, suggesting that this region is involved in muscone perception. Finally, we identified the mouse olfactory receptor, MOR215-1, that was a specific muscone receptor expressed by neurons innervating the muscone-responsive anteromedial glomeruli and also the human muscone receptor, OR5AN1. The current study documents the olfactory neural pathway in mice that senses and transmits musk signals from receptor to brain.

  17. Temporal processing in the olfactory system: can we see a smell?

    PubMed

    Gire, David H; Restrepo, Diego; Sejnowski, Terrence J; Greer, Charles; De Carlos, Juan A; Lopez-Mascaraque, Laura

    2013-05-01

    Sensory processing circuits in the visual and olfactory systems receive input from complex, rapidly changing environments. Although patterns of light and plumes of odor create different distributions of activity in the retina and olfactory bulb, both structures use what appears on the surface similar temporal coding strategies to convey information to higher areas in the brain. We compare temporal coding in the early stages of the olfactory and visual systems, highlighting recent progress in understanding the role of time in olfactory coding during active sensing by behaving animals. We also examine studies that address the divergent circuit mechanisms that generate temporal codes in the two systems, and find that they provide physiological information directly related to functional questions raised by neuroanatomical studies of Ramon y Cajal over a century ago. Consideration of differences in neural activity in sensory systems contributes to generating new approaches to understand signal processing.

  18. Critical role of GFRα1 in the development and function of the main olfactory system.

    PubMed

    Marks, Carolyn; Belluscio, Leonardo; Ibáñez, Carlos F

    2012-11-28

    Glial cell line-derived neurotrophic factor (GDNF) and its receptor GFRα1 are prominently expressed in the olfactory epithelium (OE) and olfactory bulb (OB), but their importance for olfactory system development is completely unknown. We have investigated the consequences of GFRα1 deficiency for mouse olfactory system development and function. In the OE, GFRα1 was expressed in basal precursors, immature olfactory sensory neurons (OSNs), and olfactory ensheathing cells (OECs), but was excluded from mature OSNs. The OE of newborn Gfra1 knock-out mice was thinner and contained fewer OSNs, but more dividing precursors, suggesting deficient neurogenesis. Immature OSN axon bundles were enlarged and associated OECs increased, indicating impaired migration of OECs and OSN axons. In the OB, GFRα1 was expressed in immature OSN axons and OECs of the nerve layer, as well as mitral and tufted cells, but was excluded from GABAergic interneurons. In newborn knock-outs, the nerve layer was dramatically reduced, exhibiting fewer axons and OECs. Bulbs were smaller and presented fewer and disorganized glomeruli and a significant reduction in mitral cells. Numbers of tyrosine hydroxylase-, calbindin-, and calretinin-expressing interneurons were also reduced in newborn mice lacking Gfra1. At birth, the OE and OB of Gdnf knock-out mice displayed comparable phenotypes. Similar deficits were also found in adult heterozygous Gfra1(+/-) mutants, which in addition displayed diminished responses in behavioral tests of olfactory function. We conclude that GFRα1 is critical for the development and function of the main olfactory system, contributing to the development and allocation of all major classes of neurons and glial cells.

  19. Bimodal processing of olfactory information in an amphibian nose: odor responses segregate into a medial and a lateral stream.

    PubMed

    Gliem, Sebastian; Syed, Adnan S; Sansone, Alfredo; Kludt, Eugen; Tantalaki, Evangelia; Hassenklöver, Thomas; Korsching, Sigrun I; Manzini, Ivan

    2013-06-01

    In contrast to the single sensory surface present in teleost fishes, several spatially segregated subsystems with distinct molecular and functional characteristics define the mammalian olfactory system. However, the evolutionary steps of that transition remain unknown. Here we analyzed the olfactory system of an early diverging tetrapod, the amphibian Xenopus laevis, and report for the first time the existence of two odor-processing streams, sharply segregated in the main olfactory bulb and partially segregated in the olfactory epithelium of pre-metamorphic larvae. A lateral odor-processing stream is formed by microvillous receptor neurons and is characterized by amino acid responses and Gαo/Gαi as probable signal transducers, whereas a medial stream formed by ciliated receptor neurons is characterized by responses to alcohols, aldehydes, and ketones, and Gαolf/cAMP as probable signal transducers. To reveal candidates for the olfactory receptors underlying these two streams, the spatial distribution of 12 genes from four olfactory receptor gene families was determined. Several class II and some class I odorant receptors (ORs) mimic the spatial distribution observed for the medial stream, whereas a trace amine-associated receptor closely parallels the spatial pattern of the lateral odor-processing stream. Other olfactory receptors (some class I odorant receptors and vomeronasal type 1 receptors) and odor responses (to bile acids, amines) were not lateralized, the latter not even in the olfactory bulb, suggesting an incomplete segregation. Thus, the olfactory system of X. laevis exhibits an intermediate stage of segregation and as such appears well suited to investigate the molecular driving forces behind olfactory regionalization.

  20. Olfactory impairment in the rotenone model of Parkinson’s disease is associated with bulbar dopaminergic D2 activity after REM sleep deprivation

    PubMed Central

    Rodrigues, Lais S.; Targa, Adriano D. S.; Noseda, Ana Carolina D.; Aurich, Mariana F.; Da Cunha, Cláudio; Lima, Marcelo M. S.

    2014-01-01

    Olfactory and rapid eye movement (REM) sleep deficits are commonly found in untreated subjects with a recent diagnosis of Parkinson’s disease (PD). Additionally, different studies report declines in olfactory performance during a short period of sleep deprivation. Mechanisms underlying these clinical manifestations are poorly understood, and impairment of dopamine (DA) neurotransmission in the olfactory bulb and the nigrostriatal pathway may have important roles in olfaction and REM sleep disturbances. Therefore, we hypothesized that modulation of the dopaminergic D2 receptors in the olfactory bulb could provide a more comprehensive understanding of the olfactory deficits in PD and REM sleep deprivation (REMSD). We decided to investigate the olfactory, neurochemical, and histological alterations generated through the administration of piribedil (a selective D2 agonist) or raclopride (a selective D2 antagonist) within the glomerular layer of the olfactory bulb, in rats subjected to intranigral rotenone and REMSD. Our findings provide evidence of the occurrence of a negative correlation (r = −0.52, P = 0.04) between the number of periglomerular TH-ir neurons and the bulbar levels of DA in the rotenone, but not sham, groups. A significant positive correlation (r = 0.34, P = 0.03) was observed between nigrostriatal DA levels and olfactory discrimination index (DI) for the sham groups, indicating that increased DA levels in the substantia nigra pars compacta (SNpc) are associated with enhanced olfactory discrimination performance. Also, increased levels in bulbar and striatal DA were induced by piribedil in the rotenone control and rotenone REMSD groups, consistent with reductions in the DI. The present evidence reinforce the idea that DA produced by periglomerular neurons, particularly the bulbar dopaminergic D2 receptors, is an essential participant in olfactory discrimination processes, as the SNpc, and the striatum. PMID:25520618

  1. Olfactory impairment in the rotenone model of Parkinson's disease is associated with bulbar dopaminergic D2 activity after REM sleep deprivation.

    PubMed

    Rodrigues, Lais S; Targa, Adriano D S; Noseda, Ana Carolina D; Aurich, Mariana F; Da Cunha, Cláudio; Lima, Marcelo M S

    2014-01-01

    Olfactory and rapid eye movement (REM) sleep deficits are commonly found in untreated subjects with a recent diagnosis of Parkinson's disease (PD). Additionally, different studies report declines in olfactory performance during a short period of sleep deprivation. Mechanisms underlying these clinical manifestations are poorly understood, and impairment of dopamine (DA) neurotransmission in the olfactory bulb and the nigrostriatal pathway may have important roles in olfaction and REM sleep disturbances. Therefore, we hypothesized that modulation of the dopaminergic D2 receptors in the olfactory bulb could provide a more comprehensive understanding of the olfactory deficits in PD and REM sleep deprivation (REMSD). We decided to investigate the olfactory, neurochemical, and histological alterations generated through the administration of piribedil (a selective D2 agonist) or raclopride (a selective D2 antagonist) within the glomerular layer of the olfactory bulb, in rats subjected to intranigral rotenone and REMSD. Our findings provide evidence of the occurrence of a negative correlation (r = -0.52, P = 0.04) between the number of periglomerular TH-ir neurons and the bulbar levels of DA in the rotenone, but not sham, groups. A significant positive correlation (r = 0.34, P = 0.03) was observed between nigrostriatal DA levels and olfactory discrimination index (DI) for the sham groups, indicating that increased DA levels in the substantia nigra pars compacta (SNpc) are associated with enhanced olfactory discrimination performance. Also, increased levels in bulbar and striatal DA were induced by piribedil in the rotenone control and rotenone REMSD groups, consistent with reductions in the DI. The present evidence reinforce the idea that DA produced by periglomerular neurons, particularly the bulbar dopaminergic D2 receptors, is an essential participant in olfactory discrimination processes, as the SNpc, and the striatum.

  2. Ionotropic Crustacean Olfactory Receptors

    PubMed Central

    Corey, Elizabeth A.; Bobkov, Yuriy; Ukhanov, Kirill; Ache, Barry W.

    2013-01-01

    The nature of the olfactory receptor in crustaceans, a major group of arthropods, has remained elusive. We report that spiny lobsters, Panulirus argus, express ionotropic receptors (IRs), the insect chemosensory variants of ionotropic glutamate receptors. Unlike insects IRs, which are expressed in a specific subset of olfactory cells, two lobster IR subunits are expressed in most, if not all, lobster olfactory receptor neurons (ORNs), as confirmed by antibody labeling and in situ hybridization. Ligand-specific ORN responses visualized by calcium imaging are consistent with a restricted expression pattern found for other potential subunits, suggesting that cell-specific expression of uncommon IR subunits determines the ligand sensitivity of individual cells. IRs are the only type of olfactory receptor that we have detected in spiny lobster olfactory tissue, suggesting that they likely mediate olfactory signaling. Given long-standing evidence for G protein-mediated signaling in activation of lobster ORNs, this finding raises the interesting specter that IRs act in concert with second messenger-mediated signaling. PMID:23573266

  3. The wiring diagram of a glomerular olfactory system.

    PubMed

    Berck, Matthew E; Khandelwal, Avinash; Claus, Lindsey; Hernandez-Nunez, Luis; Si, Guangwei; Tabone, Christopher J; Li, Feng; Truman, James W; Fetter, Rick D; Louis, Matthieu; Samuel, Aravinthan Dt; Cardona, Albert

    2016-01-01

    The sense of smell enables animals to react to long-distance cues according to learned and innate valences. Here, we have mapped with electron microscopy the complete wiring diagram of the Drosophila larval antennal lobe, an olfactory neuropil similar to the vertebrate olfactory bulb. We found a canonical circuit with uniglomerular projection neurons (uPNs) relaying gain-controlled ORN activity to the mushroom body and the lateral horn. A second, parallel circuit with multiglomerular projection neurons (mPNs) and hierarchically connected local neurons (LNs) selectively integrates multiple ORN signals already at the first synapse. LN-LN synaptic connections putatively implement a bistable gain control mechanism that either computes odor saliency through panglomerular inhibition, or allows some glomeruli to respond to faint aversive odors in the presence of strong appetitive odors. This complete wiring diagram will support experimental and theoretical studies towards bridging the gap between circuits and behavior. PMID:27177418

  4. Odorant-Dependent Generation of Nitric Oxide in Mammalian Olfactory Sensory Neurons

    PubMed Central

    Brunert, Daniela; Kurtenbach, Stefan; Isik, Sonnur; Benecke, Heike; Gisselmann, Günter; Schuhmann, Wolfgang; Hatt, Hanns; Wetzel, Christian H.

    2009-01-01

    The gaseous signalling molecule nitric oxide (NO) is involved in various physiological processes including regulation of blood pressure, immunocytotoxicity and neurotransmission. In the mammalian olfactory bulb (OB), NO plays a role in the formation of olfactory memory evoked by pheromones as well as conventional odorants. While NO generated by the neuronal isoform of NO synthase (nNOS) regulates neurogenesis in the olfactory epithelium, NO has not been implicated in olfactory signal transduction. We now show the expression and function of the endothelial isoform of NO synthase (eNOS) in mature olfactory sensory neurons (OSNs) of adult mice. Using NO-sensitive micro electrodes, we show that stimulation liberates NO from isolated wild-type OSNs, but not from OSNs of eNOS deficient mice. Integrated electrophysiological recordings (electro-olfactograms or EOGs) from the olfactory epithelium of these mice show that NO plays a significant role in modulating adaptation. Evidence for the presence of eNOS in mature mammalian OSNs and its involvement in odorant adaptation implicates NO as an important new element involved in olfactory signal transduction. As a diffusible messenger, NO could also have additional functions related to cross adaptation, regeneration, and maintenance of MOE homeostasis. PMID:19430528

  5. Multi-unit Recording Methods to Characterize Neural Activity in the Locust (Schistocerca Americana) Olfactory Circuits

    PubMed Central

    Saha, Debajit; Leong, Kevin; Katta, Nalin; Raman, Baranidharan

    2013-01-01

    Detection and interpretation of olfactory cues are critical for the survival of many organisms. Remarkably, species across phyla have strikingly similar olfactory systems suggesting that the biological approach to chemical sensing has been optimized over evolutionary time1. In the insect olfactory system, odorants are transduced by olfactory receptor neurons (ORN) in the antenna, which convert chemical stimuli into trains of action potentials. Sensory input from the ORNs is then relayed to the antennal lobe (AL; a structure analogous to the vertebrate olfactory bulb). In the AL, neural representations for odors take the form of spatiotemporal firing patterns distributed across ensembles of principal neurons (PNs; also referred to as projection neurons)2,3. The AL output is subsequently processed by Kenyon cells (KCs) in the downstream mushroom body (MB), a structure associated with olfactory memory and learning4,5. Here, we present electrophysiological recording techniques to monitor odor-evoked neural responses in these olfactory circuits. First, we present a single sensillum recording method to study odor-evoked responses at the level of populations of ORNs6,7. We discuss the use of saline filled sharpened glass pipettes as electrodes to extracellularly monitor ORN responses. Next, we present a method to extracellularly monitor PN responses using a commercial 16-channel electrode3. A similar approach using a custom-made 8-channel twisted wire tetrode is demonstrated for Kenyon cell recordings8. We provide details of our experimental setup and present representative recording traces for each of these techniques. PMID:23380828

  6. Fragile X Mental Retardation Protein Regulates Olfactory Sensitivity But Not Odorant Discrimination

    PubMed Central

    Schilit Nitenson, Arielle; Stackpole, Emily E.; Truszkowski, Torrey L.S.; Midroit, Maellie; Fallon, Justin R.

    2015-01-01

    Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability and is characterized by cognitive impairments and altered sensory function. It is caused by absence of fragile X mental retardation protein (FMRP), an RNA-binding protein essential for normal synaptic plasticity and function. Animal models have provided important insights into mechanisms through which loss of FMRP impacts cognitive and sensory development and function. While FMRP is highly enriched in the developing and adult olfactory bulb (OB), its role in olfactory sensory function remains poorly understood. Here, we used a mouse model of FXS, the fmr1 −/y mouse, to test whether loss of FMRP impacts olfactory discrimination, habituation, or sensitivity using a spontaneous olfactory cross-habituation task at a range of odorant concentrations. We demonstrated that fmr1 −/y mice have a significant decrease in olfactory sensitivity compared with wild type controls. When we controlled for differences in sensitivity, we found no effect of loss of FMRP on the ability to habituate to or spontaneously discriminate between odorants. These data indicate that loss of FMRP significantly alters olfactory sensitivity, but not other facets of basal olfactory function. These findings have important implications for future studies aimed at understanding the role of FMRP on sensory functioning. PMID:25917509

  7. The therapeutic potential of human olfactory-derived stem cells.

    PubMed

    Marshall, C T; Lu, C; Winstead, W; Zhang, X; Xiao, M; Harding, G; Klueber, K M; Roisen, F J

    2006-06-01

    Stem cells from fetal and adult central nervous system have been isolated and characterized, providing populations for potential replacement therapy for traumatic injury repair and neurodegenerative diseases. The regenerative capacity of the olfactory system has attracted scientific interest. Studies focusing on animal and human olfactory bulb ensheathing cells (OECs) have heightened the expectations that OECs can enhance axonal regeneration and repair demyelinating diseases. Harvest of OECs from the olfactory bulb requires highly invasive surgery, which is a major obstacle. In contrast, olfactory epithelium (OE) has a unique regenerative capacity and is readily accessible from its location in the nasal cavity, allowing for harvest without lasting damage to the donor. Adult OE contains progenitors responsible for the normal life-long continuous replacement of neurons and supporting cells. Culture techniques have been established for human OE that generate populations of mitotically active neural progenitors that form neurospheres (Roisen et al., 2001; Winstead et al., 2005). The potential application of this technology includes autologous transplantation where minimal donor material can be isolated, expanded ex vivo, and lineage restricted to a desired phenotype prior to/or after re-implantation. Furthermore, these strategies circumvent the ethical issues that arise with embryonic or fetal tissues. The long term goal is to develop procedures through which a victim of a spinal cord injury or neurodegenerative condition would serve as a source of progenitors for his/her own regenerative grafts, avoiding the need for immunosuppression and ethical controversy. In addition, these cells can provide populations for pharmacological and/or diagnostic evaluation.

  8. Coding of odor stimulus features among secondary olfactory structures.

    PubMed

    Xia, Christina Z; Adjei, Stacey; Wesson, Daniel W

    2015-07-01

    Sensory systems must represent stimuli in manners dependent upon a wealth of factors, including stimulus intensity and duration. One way the brain might handle these complex functions is to assign the tasks throughout distributed nodes, each contributing to information processing. We sought to explore this important aspect of sensory network function in the mammalian olfactory system, wherein the intensity and duration of odor exposure are critical contributors to odor perception. This is a quintessential model for exploring processing schemes given the distribution of odor information by olfactory bulb mitral and tufted cells into several anatomically distinct secondary processing stages, including the piriform cortex (PCX) and olfactory tubercle (OT), whose unique contributions to odor coding are unresolved. We explored the coding of PCX and OT neuron responses to odor intensity and duration. We found that both structures similarly partake in representing descending intensities of odors by reduced recruitment and modulation of neurons. Additionally, while neurons in the OT adapt to odor exposure, they display reduced capacity to adapt to either repeated presentations of odor or a single prolonged odor presentation compared with neurons in the PCX. These results provide insights into manners whereby secondary olfactory structures may, at least in some cases, uniquely represent stimulus features. PMID:26041832

  9. Coding of odor stimulus features among secondary olfactory structures

    PubMed Central

    Xia, Christina Z.; Adjei, Stacey

    2015-01-01

    Sensory systems must represent stimuli in manners dependent upon a wealth of factors, including stimulus intensity and duration. One way the brain might handle these complex functions is to assign the tasks throughout distributed nodes, each contributing to information processing. We sought to explore this important aspect of sensory network function in the mammalian olfactory system, wherein the intensity and duration of odor exposure are critical contributors to odor perception. This is a quintessential model for exploring processing schemes given the distribution of odor information by olfactory bulb mitral and tufted cells into several anatomically distinct secondary processing stages, including the piriform cortex (PCX) and olfactory tubercle (OT), whose unique contributions to odor coding are unresolved. We explored the coding of PCX and OT neuron responses to odor intensity and duration. We found that both structures similarly partake in representing descending intensities of odors by reduced recruitment and modulation of neurons. Additionally, while neurons in the OT adapt to odor exposure, they display reduced capacity to adapt to either repeated presentations of odor or a single prolonged odor presentation compared with neurons in the PCX. These results provide insights into manners whereby secondary olfactory structures may, at least in some cases, uniquely represent stimulus features. PMID:26041832

  10. Penguins reduced olfactory receptor genes common to other waterbirds

    PubMed Central

    Lu, Qin; Wang, Kai; Lei, Fumin; Yu, Dan; Zhao, Huabin

    2016-01-01

    The sense of smell, or olfaction, is fundamental in the life of animals. However, penguins (Aves: Sphenisciformes) possess relatively small olfactory bulbs compared with most other waterbirds such as Procellariiformes and Gaviiformes. To test whether penguins have a reduced reliance on olfaction, we analyzed the draft genome sequences of the two penguins, which diverged at the origin of the order Sphenisciformes; we also examined six closely related species with available genomes, and identified 29 one-to-one orthologous olfactory receptor genes (i.e. ORs) that are putatively functionally conserved and important across the eight birds. To survey the 29 one-to-one orthologous ORs in penguins and their relatives, we newly generated 34 sequences that are missing from the draft genomes. Through the analysis of totaling 378 OR sequences, we found that, of these functionally important ORs common to other waterbirds, penguins have a significantly greater percentage of OR pseudogenes than other waterbirds, suggesting a reduction of olfactory capability. The penguin-specific reduction of olfactory capability arose in the common ancestor of penguins between 23 and 60 Ma, which may have resulted from the aquatic specializations for underwater vision. Our study provides genetic evidence for a possible reduction of reliance on olfaction in penguins. PMID:27527385

  11. Penguins reduced olfactory receptor genes common to other waterbirds.

    PubMed

    Lu, Qin; Wang, Kai; Lei, Fumin; Yu, Dan; Zhao, Huabin

    2016-08-16

    The sense of smell, or olfaction, is fundamental in the life of animals. However, penguins (Aves: Sphenisciformes) possess relatively small olfactory bulbs compared with most other waterbirds such as Procellariiformes and Gaviiformes. To test whether penguins have a reduced reliance on olfaction, we analyzed the draft genome sequences of the two penguins, which diverged at the origin of the order Sphenisciformes; we also examined six closely related species with available genomes, and identified 29 one-to-one orthologous olfactory receptor genes (i.e. ORs) that are putatively functionally conserved and important across the eight birds. To survey the 29 one-to-one orthologous ORs in penguins and their relatives, we newly generated 34 sequences that are missing from the draft genomes. Through the analysis of totaling 378 OR sequences, we found that, of these functionally important ORs common to other waterbirds, penguins have a significantly greater percentage of OR pseudogenes than other waterbirds, suggesting a reduction of olfactory capability. The penguin-specific reduction of olfactory capability arose in the common ancestor of penguins between 23 and 60 Ma, which may have resulted from the aquatic specializations for underwater vision. Our study provides genetic evidence for a possible reduction of reliance on olfaction in penguins.

  12. Early Expression of Odorant Receptors Distorts the Olfactory Circuitry

    PubMed Central

    Nguyen, Minh Q.; Marks, Carolyn A.; Belluscio, Leonardo; Ryba, Nicholas J. P.

    2010-01-01

    The odor response properties of a mammalian olfactory sensory neuron (OSN) are determined by the tightly regulated expression of a single member of a very large family of odorant receptors (ORs). The OR also plays an important role in focusing the central projections of all OSNs expressing that particular receptor to a pair of stereotypic locations (glomeruli) in each olfactory bulb (OB), thus creating a spatial map of odor responses in the brain. Here we show that when initiated late in neural development, transgenic expression of one OR in almost all OSNs has little influence on the architecture of the OB. In contrast, early OR-transgene expression (mediated by the Gγ8-promoter) in 50–70% of OSNs grossly distorts the morphology of glomeruli and alters the projection patterns of many residual OSNs not expressing the transgene. Interestingly, this disruption of targeting persists in adult animals despite down-regulation of Gγ8 and transgenic OR expression that occurs as olfactory neurogenesis declines. Indeed, functional imaging studies reveal a dramatic decrease in the complexity of responses to odorants in adult Gγ8-transgenic OR mice. Thus, we show that initiation of transgenic OR-expression early in the development of OSNs, rather than just the extent of transgene expression, determines its effectiveness at modifying OB anatomy and function. Taken together these data imply that OR-expression timing needs to be very tightly controlled to achieve the precise wiring and function of the mammalian olfactory system. PMID:20610762

  13. Penguins reduced olfactory receptor genes common to other waterbirds.

    PubMed

    Lu, Qin; Wang, Kai; Lei, Fumin; Yu, Dan; Zhao, Huabin

    2016-01-01

    The sense of smell, or olfaction, is fundamental in the life of animals. However, penguins (Aves: Sphenisciformes) possess relatively small olfactory bulbs compared with most other waterbirds such as Procellariiformes and Gaviiformes. To test whether penguins have a reduced reliance on olfaction, we analyzed the draft genome sequences of the two penguins, which diverged at the origin of the order Sphenisciformes; we also examined six closely related species with available genomes, and identified 29 one-to-one orthologous olfactory receptor genes (i.e. ORs) that are putatively functionally conserved and important across the eight birds. To survey the 29 one-to-one orthologous ORs in penguins and their relatives, we newly generated 34 sequences that are missing from the draft genomes. Through the analysis of totaling 378 OR sequences, we found that, of these functionally important ORs common to other waterbirds, penguins have a significantly greater percentage of OR pseudogenes than other waterbirds, suggesting a reduction of olfactory capability. The penguin-specific reduction of olfactory capability arose in the common ancestor of penguins between 23 and 60 Ma, which may have resulted from the aquatic specializations for underwater vision. Our study provides genetic evidence for a possible reduction of reliance on olfaction in penguins. PMID:27527385

  14. Developing a sense of scents: Plasticity in olfactory placode formation

    PubMed Central

    Whitlock, K. E.

    2008-01-01

    The sense organs of the vertebrate head arise predominantly from sensory placodes. The sensory placodes have traditionally been grouped as structures that share common developmental and evolutionary characteristics. In attempts to build a coherent model for development of all placodes, the fascinating differences that make placodes unique are often overlooked. Here I review olfactory placode development with special attention to the origin and cell movements that generate the olfactory placode, the derivatives of this sensory placode, and the degree to which it shows plasticity during development. Next, through comparison with adenohypophyseal, and lens placodes I suggest we revise our thinking and terminology for these anterior placodes, specifically by: 1) referring to the peripheral olfactory sensory system as neural ectoderm because it expresses the same series of genes involved in neural differentiation and differentiates in tandem with the olfactory bulb, 2) grouping the anterior placodes with their corresponding central nervous system structures and emphasizing patterning mechanisms shared between placodes and these targets. Sensory systems did not arise independent of the central nervous system; they are part of a functional unit composed of peripheral sensory structures and their targets. By expanding our analyses of sensory system development to also include cell movements, gene expression and morphological changes observed in this functional unit, we will better understand the evolution of sensory structures. PMID:18331896

  15. Developing a sense of scents: plasticity in olfactory placode formation.

    PubMed

    Whitlock, K E

    2008-03-18

    The sense organs of the vertebrate head arise predominantly from sensory placodes. The sensory placodes have traditionally been grouped as structures that share common developmental and evolutionary characteristics. In attempts to build a coherent model for development of all placodes, the fascinating differences that make placodes unique are often overlooked. Here I review olfactory placode development with special attention to the origin and cell movements that generate the olfactory placode, the derivatives of this sensory placode, and the degree to which it shows plasticity during development. Next, through comparison with adenohypophyseal, and lens placodes I suggest we revise our thinking and terminology for these anterior placodes, specifically by: (1) referring to the peripheral olfactory sensory system as neural ectoderm because it expresses the same series of genes involved in neural differentiation and differentiates in tandem with the olfactory bulb, and (2) grouping the anterior placodes with their corresponding central nervous system structures and emphasizing patterning mechanisms shared between placodes and these targets. Sensory systems did not arise independent of the central nervous system; they are part of a functional unit composed of peripheral sensory structures and their targets. By expanding our analyses of sensory system development to also include cell movements, gene expression and morphological changes observed in this functional unit, we will better understand the evolution of sensory structures. PMID:18331896

  16. Olfactory Learning in Drosophila

    PubMed Central

    Busto, Germain U.; Cervantes-Sandoval, Isaac; Davis, Ronald L.

    2012-01-01

    Studies of olfactory learning in Drosophila have provided key insights into the brain mechanisms underlying learning and memory. One type of olfactory learning, olfactory classical conditioning, consists of learning the contingency between an odor with an aversive or appetitive stimulus. This conditioning requires the activity of molecules that can integrate the two types of sensory information, the odorant as the conditioned stimulus and the aversive or appetitive stimulus as the unconditioned stimulus, in brain regions where the neural pathways for the two stimuli intersect. Compelling data indicate that a particular form of adenylyl cyclase functions as a molecular integrator of the sensory information in the mushroom body neurons. The neuronal pathway carrying the olfactory information from the antennal lobes to the mushroom body is well described. Accumulating data now show that some dopaminergic neurons provide information about aversive stimuli and octopaminergic neurons about appetitive stimuli to the mushroom body neurons. Inhibitory inputs from the GABAergic system appear to gate olfactory information to the mushroom bodies and thus control the ability to learn about odors. Emerging data obtained by functional imaging procedures indicate that distinct memory traces form in different brain regions and correlate with different phases of memory. The results from these and other experiments also indicate that cross talk between mushroom bodies and several other brain regions is critical for memory formation. PMID:21186278

  17. In vivo visualization of olfactory pathophysiology induced by intranasal cadmium instillation in mice

    PubMed Central

    Czarnecki, Lindsey A.; Moberly, Andrew H.; Rubinstein, Tom; Turkel, Daniel J.; Pottackal, Joseph; McGann, John P.

    2013-01-01

    Intranasal exposure to cadmium has been related to olfactory dysfunction in humans and to nasal epithelial damage and altered odorant-guided behavior in rodent models. The pathophysiology underlying these deficits has not been fully elucidated. Here we use optical imaging techniques to visualize odorant-evoked neurotransmitter release from the olfactory nerve into the brain’s olfactory bulbs in vivo in mice. Intranasal cadmium chloride instillations reduced this sensory activity by up to 91% in a dose-dependent manner. In the olfactory bulbs, afferents from the olfactory epithelium could be quantified by their expression of a genetically-encoded fluorescent marker for olfactory marker protein. At the highest dose tested, cadmium exposure reduced the density of these projections by 20%. In a behavioral psychophysical task, mice were trained to sample from an odor port and make a response when they detected an odorant against a background of room air. After intranasal cadmium exposure, mice were unable to detect the target odor. These experiments serve as proof of concept for a new approach to the study of the neural effects of inhaled toxicants. The use of in vivo functional imaging of the neuronal populations exposed to the toxicant permits the direct observation of primary pathophysiology. In this study optical imaging revealed significant reductions in odorant-evoked release from the olfactory nerve at a cadmium chloride dose two orders of magnitude less than that required to induce morphological changes in the nerve in the same animals, demonstrating that it is a more sensitive technique for assessing the consequences of intranasal neurotoxicant exposure. This approach is potentially useful in exploring the effects of any putative neurotoxicant that can be delivered intranasally. PMID:21443902

  18. Vanadium exposure induces olfactory dysfunction in an animal model of metal neurotoxicity.

    PubMed

    Ngwa, Hilary Afeseh; Kanthasamy, Arthi; Jin, Huajun; Anantharam, Vellareddy; Kanthasamy, Anumantha G

    2014-07-01

    Epidemiological evidence indicates chronic environmental exposure to transition metals may play a role in chronic neurodegenerative conditions such as Parkinson's disease (PD). Chronic inhalation exposure to welding fumes containing metal mixtures may be associated with development of PD. A significant amount of vanadium is present in welding fumes, as vanadium pentoxide (V2O5), and incorporation of vanadium in the production of high strength steel has become more common. Despite the increased vanadium use in recent years, the neurotoxicological effects of this metal are not well characterized. Recently, we demonstrated that V2O5 induces dopaminergic neurotoxicity via protein kinase C delta (PKCδ)-dependent oxidative signaling mechanisms in dopaminergic neuronal cells. Since anosmia (inability to perceive odors) and non-motor deficits are considered to be early symptoms of neurological diseases, in the present study, we examined the effect of V2O5 on the olfactory bulb in animal models. To mimic the inhalation exposure, we intranasally administered C57 black mice a low-dose of 182μg of V2O5 three times a week for one month, and behavioral, neurochemical and biochemical studies were performed. Our results revealed a significant decrease in olfactory bulb weights, tyrosine hydroxylase (TH) levels, levels of dopamine (DA) and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC) and increases in astroglia of the glomerular layer of the olfactory bulb in the treatment groups relative to vehicle controls. Neurochemical changes were accompanied by impaired olfaction and locomotion. These findings suggest that nasal exposure to V2O5 adversely affects olfactory bulbs, resulting in neurobehavioral and neurochemical impairments. These results expand our understanding of vanadium neurotoxicity in environmentally-linked neurological conditions.

  19. On the olfactory anatomy in an archaic whale (Protocetidae, Cetacea) and the minke whale Balaenoptera acutorostrata (Balaenopteridae, Cetacea).

    PubMed

    Godfrey, Stephen J; Geisler, Jonathan; Fitzgerald, Erich M G

    2013-02-01

    The structure of the olfactory apparatus is not well known in both archaic and extant whales; the result of poor preservation in most fossils and locational isolation deep within the skulls in both fossil and Recent taxa. Several specimens now shed additional light on the subject. A partial skull of an archaic cetacean is reported from the Pamunkey River, Virginia, USA. The specimen probably derives from the upper middle Eocene (Piney Point Formation) and is tentatively assigned to the Protocetidae. Uncrushed cranial cavities associated with the olfactory apparatus were devoid of sediment. CT scans clearly reveal the dorsal nasal meatus, ethmoturbinates within the olfactory recess, the cribriform plate, the area occupied by the olfactory bulbs, and the olfactory nerve tract. Several sectioned skulls of the minke whale (Balaenoptera acutorostrata) were also examined, and olfactory structures are remarkably similar to those observed in the fossil skull from the Pamunkey River. One important difference between the two is that the fossil specimen has an elongate olfactory nerve tract. The more forward position of the external nares in extant balaenopterids when compared with those of extant odontocetes is interpreted to be the result of the need to retain a functional olfactory apparatus and the forward position of the supraoccipital/cranial vertex. An increase in the distance between the occipital condyles and the vertex in balaenopterids enhances the mechanical advantage of the epaxial musculature that inserts on the occiput, a specialization that likely stabilizes the head of these enormous mammals during lunge feeding.

  20. Olfactory dysfunction in Alzheimer's disease.

    PubMed

    Zou, Yong-Ming; Lu, Da; Liu, Li-Ping; Zhang, Hui-Hong; Zhou, Yu-Ying

    2016-01-01

    Alzheimer's disease (AD) is a common neurodegenerative disorder with the earliest clinical symptom of olfactory dysfunction, which is a potential clinical marker for AD severity and progression. However, many questions remain unanswered. This article reviews relevant research on olfactory dysfunction in AD and evaluates the predictive value of olfactory dysfunction for the epidemiological, pathophysiological, and clinical features of AD, as well as for the conversion of cognitive impairment to AD. We summarize problems of existing studies and provide a useful reference for further studies in AD olfactory dysfunction and for clinical applications of olfactory testing. PMID:27143888

  1. Olfactory sensitivity in mammalian species.

    PubMed

    Wackermannová, M; Pinc, L; Jebavý, L

    2016-07-18

    Olfaction enables most mammalian species to detect and discriminate vast numbers of chemical structures called odorants and pheromones. The perception of such chemical compounds is mediated via two major olfactory systems, the main olfactory system and the vomeronasal system, as well as minor systems, such as the septal organ and the Grueneberg ganglion. Distinct differences exist not only among species but also among individuals in terms of their olfactory sensitivity; however, little is known about the mechanisms that determine these differences. In research on the olfactory sensitivity of mammals, scientists thus depend in most cases on behavioral testing. In this article, we reviewed scientific studies performed on various mammalian species using different methodologies and target chemical substances. Human and non-human primates as well as rodents and dogs are the most frequently studied species. Olfactory threshold studies on other species do not exist with the exception of domestic pigs. Olfactory testing performed on seals, elephants, and bats focused more on discriminative abilities than on sensitivity. An overview of olfactory sensitivity studies as well as olfactory detection ability in most studied mammalian species is presented here, focusing on comparable olfactory detection thresholds. The basics of olfactory perception and olfactory sensitivity factors are also described. PMID:27070753

  2. Olfactory Receptor Subgenomes Linked with Broad Ecological Adaptations in Sauropsida.

    PubMed

    Khan, Imran; Yang, Zhikai; Maldonado, Emanuel; Li, Cai; Zhang, Guojie; Gilbert, M Thomas P; Jarvis, Erich D; O'Brien, Stephen J; Johnson, Warren E; Antunes, Agostinho

    2015-11-01

    Olfactory receptors (ORs) govern a prime sensory function. Extant birds have distinct olfactory abilities, but the molecular mechanisms underlining diversification and specialization remain mostly unknown. We explored OR diversity in 48 phylogenetic and ecologically diverse birds and 2 reptiles (alligator and green sea turtle). OR subgenomes showed species- and lineage-specific variation related with ecological requirements. Overall 1,953 OR genes were identified in reptiles and 16,503 in birds. The two reptiles had larger OR gene repertoires (989 and 964 genes, respectively) than birds (182-688 genes). Overall, birds had more pseudogenes (7,855) than intact genes (1,944). The alligator had significantly more functional genes than sea turtle, likely because of distinct foraging habits. We found rapid species-specific expansion and positive selection in OR14 (detects hydrophobic compounds) in birds and in OR51 and OR52 (detect hydrophilic compounds) in sea turtle, suggestive of terrestrial and aquatic adaptations, respectively. Ecological partitioning among birds of prey, water birds, land birds, and vocal learners showed that diverse ecological factors determined olfactory ability and influenced corresponding olfactory-receptor subgenome. OR5/8/9 was expanded in predatory birds and alligator, suggesting adaptive specialization for carnivory. OR families 2/13, 51, and 52 were correlated with aquatic adaptations (water birds), OR families 6 and 10 were more pronounced in vocal-learning birds, whereas most specialized land birds had an expanded OR family 14. Olfactory bulb ratio (OBR) and OR gene repertoire were correlated. Birds that forage for prey (carnivores/piscivores) had relatively complex OBR and OR gene repertoires compared with modern birds, including passerines, perhaps due to highly developed cognitive capacities facilitating foraging innovations. PMID:26219582

  3. An olfactory neuronal network for vapor recognition in an artificial nose.

    PubMed

    White, J; Dickinson, T A; Walt, D R; Kauer, J S

    1998-04-01

    Odorant sensitivity and discrimination in the olfactory system appear to involve extensive neural processing of the primary sensory inputs from the olfactory epithelium. To test formally the functional consequences of such processing, we implemented in an artificial chemosensing system a new analytical approach that is based directly on neural circuits of the vertebrate olfactory system. An array of fiber-optic chemosensors, constructed with response properties similar to those of olfactory sensory neurons, provide time-varying inputs to a computer simulation of the olfactory bulb (OB). The OB simulation produces spatiotemporal patterns of neuronal firing that vary with vapor type. These patterns are then recognized by a delay line neural network (DLNN). In the final output of these two processing steps, vapor identity is encoded by the spatial patterning of activity across units in the DLNN, and vapor intensity is encoded by response latency. The OB-DLNN combination thus separates identity and intensity information into two distinct codes carried by the same output units, enabling discrimination among organic vapors over a range of input signal intensities. In addition to providing a well-defined system for investigating olfactory information processing, this biologically based neuronal network performs better than standard feed-forward neural networks in discriminating vapors when small amounts of training data are used.

  4. Olfactory nerve--a novel invasion route of Neisseria meningitidis to reach the meninges.

    PubMed

    Sjölinder, Hong; Jonsson, Ann-Beth

    2010-11-18

    Neisseria meningitidis is a human-specific pathogen with capacity to cause septic shock and meningitis. It has been hypothesized that invasion of the central nervous system (CNS) is a complication of a bacteremic condition. In this study, we aimed to characterize the invasion route of N. meningitidis to the CNS. Using an intranasally challenged mouse disease model, we found that twenty percent of the mice developed lethal meningitis even though no bacteria could be detected in blood. Upon bacterial infection, epithelial lesions and redistribution of intracellular junction protein N-cadherin were observed at the nasal epithelial mucosa, especially at the olfactory epithelium, which is functionally and anatomically connected to the CNS. Bacteria were detected in the submucosa of the olfactory epithelium, along olfactory nerves in the cribriform plate, at the olfactory bulb and subsequently at the meninges and subarachnoid space. Furthermore, our data suggest that a threshold level of bacteremia is required for the development of meningococcal sepsis. Taken together, N. meningitidis is able to pass directly from nasopharynx to meninges through the olfactory nerve system. This study enhances our understanding how N. meningitidis invades the meninges. The nasal olfactory nerve system may be a novel target for disease prevention that can improve outcome and survival.

  5. Neural circuits containing olfactory neurons are involved in the prepulse inhibition of the startle reflex in rats

    PubMed Central

    Niu, Haichen; He, Xiaobin; Zhou, Ting; Shi, Xi; Zhang, Qiang; Zhang, Zhijian; Qiao, Yuehua; Xu, Fuqiang; Hu, Min

    2015-01-01

    Many neuropsychiatric disorders, such as schizophrenia, have been associated with olfactory dysfunction and abnormalities in the prepulse inhibition (PPI) response to a startle reflex. However, whether these two abnormalities could be related is unclear. The present investigations were designed to determine whether theblockage of olfactory sensory input by zinc sulfate infusion in the olfactory naris (0.5 ml, 0.17 M, ZnE) can disturb the PPI response. Furthermore, a bilateral microinjection of lidocaine/MK801 in the olfactory bulb (OB) was administered to examine whether the blockage of olfactory sensory input could impair the PPI response. To identify the neural projection between olfaction and PPI-related areas, trans-synaptic retrograde tracing with the recombinant pseudorabies virus (PRV) was used. Our results demonstrated that blockage of olfactory sensory input could disturb olfactory behavior. In the function studies, we demonstrated that blockage of olfactory sensory input could impair the pre-pulse inhibition of the startle response following decreased c-Fos expression in relevant brain regions during the PPI responses. Furthermore, similar and more robust findings indicated that blockage of olfactory sensory input by microinjection of lidocaine/MK801 in the OB could impair the PPI response. In the circuit-level studies, we demonstrated that trans-synaptic retrograde tracing with PRV exhibited a large portion of labeled neurons in several regions of the olfactory cortices from the pedunculopontine tegmental nucleus (PPTg). Thus, these data suggest that the olfactory system participates in the PPI regulating fields and plays a role in the pre-pulse inhibition of the startle response in rats. PMID:25859195

  6. From Batteries and Bulbs to High Tech.

    ERIC Educational Resources Information Center

    Schwartz, Maurice L.; Schwartz, Ivan C.

    1986-01-01

    Presents a new, high-technology approach to making bulbs light in series and parallel circuits. Contains diagrams that illustrate the circuit patterns. Provides suggestions for applying the electronic principles that were addressed in the activities. (ML)

  7. Light On the Behavior of Light Bulbs.

    ERIC Educational Resources Information Center

    Armstrong, H. L.

    1985-01-01

    Discusses a problem (on page 523 of "College Physics," by Sears, Zemansky, and Young, published by Addison-Wesley, 1980) concerning light bulbs and resistance. Shows why the assumption of constant resistance is unrealistic and provides guidelines for revision. (DH)

  8. The Amaryllis--From Bulb to Blossom.

    ERIC Educational Resources Information Center

    Radue, Anna K.

    1991-01-01

    Describes the life cycle of the Amaryllis plant from bulb to blossom. Suggests 12 activities in which students monitor plant growth, examine plant parts, make drawings of the plant, and eat flowers of other plants. (MDH)

  9. Id2 IS REQUIRED FOR SPECIFICATION OF DOPAMINERGIC NEURONS DURING ADULT OLFACTORY NEUROGENESIS

    PubMed Central

    Havrda, Matthew C.; Harris, Brent T.; Mantani, Akio; Ward, Nora M.; Paolella, Brenton R.; Cuzon, Verginia C.; Yeh, Hermes H.; Israel, Mark A.

    2009-01-01

    Understanding the biology of adult neural stem cells has important implications for nervous system development and may contribute to our understanding of neurodegenerative disorders and their treatment. We have characterized the process of olfactory neurogenesis in adult mice lacking Inhibitor of DNA Binding 2 (Id2). We found a diminished olfactory bulb containing reduced numbers of granular and periglomerular neurons with a distinct paucity of dopaminergic periglomerular neurons. While no deficiency of the stem cell compartment was detectable, migrating neuroblasts in Id2−/− mutant mice prematurely undergo astroglial differentiation within a disorganized rostral migratory stream. Further, when evaluated in vitro loss of Id2 results in decreased proliferation of neural progenitors and decreased expression of the Hes1 and Mash1 transcription factors, known mediators of neuronal differentiation. These data support a novel role for sustained Id2 expression in migrating neural progenitors mediating olfactory dopaminergic neuronal differentiation in adult animals. PMID:19109490

  10. Rapid and continuous activity-dependent plasticity of olfactory sensory input

    PubMed Central

    Cheetham, Claire E. J.; Park, Una; Belluscio, Leonardo

    2016-01-01

    Incorporation of new neurons enables plasticity and repair of circuits in the adult brain. Adult neurogenesis is a key feature of the mammalian olfactory system, with new olfactory sensory neurons (OSNs) wiring into highly organized olfactory bulb (OB) circuits throughout life. However, neither when new postnatally generated OSNs first form synapses nor whether OSNs retain the capacity for synaptogenesis once mature, is known. Therefore, how integration of adult-born OSNs may contribute to lifelong OB plasticity is unclear. Here, we use a combination of electron microscopy, optogenetic activation and in vivo time-lapse imaging to show that newly generated OSNs form highly dynamic synapses and are capable of eliciting robust stimulus-locked firing of neurons in the mouse OB. Furthermore, we demonstrate that mature OSN axons undergo continuous activity-dependent synaptic remodelling that persists into adulthood. OSN synaptogenesis, therefore, provides a sustained potential for OB plasticity and repair that is much faster than OSN replacement alone. PMID:26898529

  11. Odorant response properties of individual neurons in an olfactory glomerular module

    PubMed Central

    Kikuta, Shu; Fletcher, Max L.; Homma, Ryota; Yamasoba, Tatsuya; Nagayama, Shin

    2013-01-01

    Summary Neuronal networks that are directly associated with glomeruli in the olfactory bulb are thought to comprise functional modules. However, this has not yet been experimentally proven. In this study, we explored the anatomical and functional architecture of glomerular modules using in vivo two-photon calcium imaging. Surprisingly, the deep portions of the glomerular modules showed considerable spatial overlap with other modules. Juxtaglomerular cells showed similar excitatory odorant response profiles to presynaptic olfactory sensory neuron inputs. Mitral cells exhibited a more sharply tuned molecular receptive range compared to juxtaglomerular cells, and their odorant response profiles varied depending on their interneuronal horizontal distances. These data suggest that glomerular modules are composed of functionally distinct neurons, and that homogenous odor inputs to each glomerulus may be parsed and processed in different fashions within the modules before being sent to higher olfactory centers. PMID:23522047

  12. Fluorescent light bulbs - energy saver or environmental hazard?

    SciTech Connect

    Christenson, S.M.

    1995-03-01

    Businesses and homeowners have installed millions of fluorescent light bulbs in buildings around the country in the last few decades. Because fluorescent light bulbs are energy efficient and save electricity, environmentalists and governmental officials - including U.S. EPA - have promoted their use. Yet, fluorescent bulbs raise environmental concerns of their own. When these bulbs burn out, environmental and facility managers face complex issues about whether the old bulbs are regulated as hazardous waste.

  13. Continuous Neural Plasticity in the Olfactory Intrabulbar Circuitry

    PubMed Central

    Cummings, Diana M.; Belluscio, Leonardo

    2012-01-01

    In the mammalian brain each olfactory bulb contains two mirror-symmetric glomerular maps linked through a set of reciprocal intrabulbar projections. These projections connect isofunctional odor columns through synapses in the internal plexiform layer (IPL) to produce an intrabulbar map. Developmental studies show that initially intrabulbar projections broadly target the IPL on the opposite side of the bulb and refine postnatally to their adult precision by 7 weeks of age in an activity-dependent manner (Marks et al., 2006). In this study, we sought to determine the capacity of intrabulbar map to recover its precision after disruption. Using reversible naris closure in both juvenile and adult mice, we distorted the intrabulbar map and then removed the blocks for varying survival periods. Our results reveal that returning normal olfactory experience can indeed drive the re-refinement of intrabulbar projections but requires 9 weeks. Since activity also affects olfactory sensory neurons (OSNs) (Suh et al., 2006), we further examined the consequence of activity deprivation on P2-expressing OSNs and their associated glomeruli. Our findings indicate that while naris closure caused a marked decrease in P2-OSN number and P2-glomerular volume, axonal convergence was not lost and both were quickly restored within 3 weeks. By contrast, synaptic contacts within the IPL also decreased with sensory deprivation but required at least 6 weeks to recover. Thus, we conclude that recovery of the glomerular map precedes and likely drives the refinement of the intrabulbar map while IPL contacts recover gradually, possibly setting the pace for intrabulbar circuit restoration. PMID:20610751

  14. Primary culture of embryonic rat olfactory receptor neurons.

    PubMed

    Micholt, Evelien; Jans, Danny; Callewaert, Geert; Bartic, Carmen; Lammertyn, Jeroen; Nicolai, Bart

    2012-12-01

    Embryonic cells are very robust in surviving dissection and culturing protocols and easily adapt to their in vitro environment. Despite these advantages, research in the olfactory field on cultured embryonic olfactory neurons is sparse. In this study, two primary rat olfactory explant cultures of different embryonic d (E17 and E20) were established, comprising epithelium and bulb. The functionality of these neurons was tested by measuring intracellular calcium responses to cAMP-inducing agents forskolin (FSK) and 3-isobutyl-1-methylxanthine (IBMX) with fluorescence microscopy. For E17, the responsive cell fraction increased over time, from an initial 3% at the 1 d in vitro (DIV) to a maximum of 19% at 11 DIV. The response of E20 neurons fluctuated over time around a more or less stable 13%. A logistic regression analysis indicated a significant difference between both embryonic d in the response to FSK + IBMX. In addition, of these functional neurons, 23.3% of E17 and 54.3% of E20 cultures were responsive to the odorant isoamyl acetate. PMID:23150136

  15. Chemotopic Odorant Coding in a Mammalian Olfactory System

    PubMed Central

    Johnson, Brett A.; Leon, Michael

    2008-01-01

    Systematic mapping studies involving 365 odorant chemicals have shown that glomerular responses in the rat olfactory bulb are organized spatially in patterns that are related to the chemistry of the odorant stimuli. This organization involves the spatial clustering of principal responses to numerous odorants that share key aspects of chemistry such as functional groups, hydrocarbon structural elements, and/or overall molecular properties related to water solubility. In several of the clusters, responses shift progressively in position according to odorant carbon chain length. These response domains appear to be constructed from orderly projections of sensory neurons in the olfactory epithelium and may also involve chromatography across the nasal mucosa. The spatial clustering of glomerular responses may serve to “tune” the principal responses of bulbar projection neurons by way of inhibitory interneuronal networks, allowing the projection neurons to respond to a narrower range of stimuli than their associated sensory neurons. When glomerular activity patterns are viewed relative to the overall level of glomerular activation, the patterns accurately predict the perception of odor quality, thereby supporting the notion that spatial patterns of activity are the key factors underlying that aspect of the olfactory code. A critical analysis suggests that alternative coding mechanisms for odor quality, such as those based on temporal patterns of responses, enjoy little experimental support. PMID:17480025

  16. Chronic inhibition of nitric oxide synthesis enhances both subventricular zone neurogenesis and olfactory learning in adult mice.

    PubMed

    Romero-Grimaldi, Carmen; Gheusi, Gilles; Lledo, Pierre-Marie; Estrada, Carmen

    2006-11-01

    The ability to generate new neurons during the course of adult life is preserved in the subventricular zone of the lateral ventricles and the dentate gyrus of the hippocampus in the mammalian brain. These two regions constitute specifically regulated neurogenic niches, and provide newborn neurons involved in olfactory and spatial learning, respectively. Nitric oxide (NO) is a negative regulator of neurogenesis in the subventricular zone, whereas its role in the dentate gyrus remains controversial. Using systemic administration of NO synthase (NOS) inhibitors to chronically inhibit NO production, we increased neural precursor proliferation in the subventricular zone as well as neurogenesis in the olfactory bulb, without modifying the number of mitotic cells or the granular cell layer thickness in the dentate gyrus. The same treatment specifically improved olfactory learning performance, whereas spatial learning and memory was unchanged, thus demonstrating that olfactory memory is closely associated with the level of ongoing neurogenesis in the subventricular zone-olfactory bulb. The anatomical specificity of the NOS inhibitor actions was not due to differences in the availability of NO, as demonstrated by immunohistochemical detection of neuronal NOS and S-nitrosylated proteins in both regions. Remarkably, the distinct NO sensitivity might result from a differential expression of epidermal growth factor receptor in precursor cells in both regions, as the proliferative effect of NOS inhibitors in the subventricular zone was restricted to the cells that expressed this receptor.

  17. Attention and Olfactory Consciousness

    PubMed Central

    Keller, Andreas

    2011-01-01

    Understanding the relation between attention and consciousness is an important part of our understanding of consciousness. Attention, unlike consciousness, can be systematically manipulated in psychophysical experiments and a law-like relation between attention and consciousness is waiting to be discovered. Most attempts to discover the nature of this relation are focused on a special type of attention: spatial visual attention. In this review I want to introduce another type of attention to the discussion: attention to the olfactory modality. I will first clarify the position of attention to smells in a general taxonomy of attention. I will then review the mechanisms and neuroanatomy of attention and consciousness in the olfactory system before using the newly introduced system to provide evidence that attention is necessary for consciousness. PMID:22203813

  18. Modulation of olfactory sensitivity and glucose-sensing by the feeding state in obese Zucker rats

    PubMed Central

    Aimé, Pascaline; Palouzier-Paulignan, Brigitte; Salem, Rita; Al Koborssy, Dolly; Garcia, Samuel; Duchamp, Claude; Romestaing, Caroline; Julliard, A. Karyn

    2014-01-01

    The Zucker fa/fa rat has been widely used as an animal model to study obesity, since it recapitulates most of its behavioral and metabolic dysfunctions, such as hyperphagia, hyperglycemia and insulin resistance. Although it is well established that olfaction is under nutritional and hormonal influences, little is known about the impact of metabolic dysfunctions on olfactory performances and glucose-sensing in the olfactory system of the obese Zucker rat. In the present study, using a behavioral paradigm based on a conditioned olfactory aversion, we have shown that both obese and lean Zucker rats have a better olfactory sensitivity when they are fasted than when they are satiated. Interestingly, the obese Zucker rats displayed a higher olfactory sensitivity than their lean controls. By investigating the molecular mechanisms involved in glucose-sensing in the olfactory system, we demonstrated that sodium-coupled glucose transporters 1 (SGLT1) and insulin dependent glucose transporters 4 (GLUT4) are both expressed in the olfactory bulb (OB). By comparing the expression of GLUT4 and SGLT1 in OB of obese and lean Zucker rats, we found that only SGLT1 is regulated in genotype-dependent manner. Next, we used glucose oxidase biosensors to simultaneously measure in vivo the extracellular fluid glucose concentrations ([Gluc]ECF) in the OB and the cortex. Under metabolic steady state, we have determined that the OB contained twice the amount of glucose found in the cortex. In both regions, the [Gluc]ECF was 2 fold higher in obese rats compared to their lean controls. Under induced dynamic glycemia conditions, insulin injection produced a greater decrease of [Gluc]ECF in the OB than in the cortex. Glucose injection did not affect OB [Gluc]ECF in Zucker fa/fa rats. In conclusion, these results emphasize the importance of glucose for the OB network function and provide strong arguments towards establishing the OB glucose-sensing as a key factor for sensory olfactory processing

  19. Sadness might isolate you in a non-smelling world: olfactory perception and depression

    PubMed Central

    Schablitzky, Sylvia; Pause, Bettina M.

    2014-01-01

    Major depressive disorder (MDD) occurs with a high prevalence among mental illnesses. MDD patients experience sadness and hopelessness, with blunted affective reactivity. However, such depressive episodes are also key symptoms in other depressive disorders, like Bipolar Disorder (BPD) or Seasonal Affective Disorder (SAD). Moreover, depressive symptoms can also be found in healthy individuals, but are experienced as less severe or for a shorter duration than in patients. Here, it is aimed to summarize studies investigating odor perception in depression, including depressive states in healthy individuals and patient populations. Odor perception in depression has been assessed with psychophysical methods (olfactory sensitivity, odor identification, and discrimination), and odor ratings (intensity, emotional valence, familiarity). In addition, some studies investigated affective reactions to odors, and physiological and anatomical correlates of odor perception in depression. The summary reveals that MDD is associated with reduced olfactory sensitivity. However, odor identification and discrimination scores seem to be unaffected by depression. The reduced olfactory sensitivity might be associated with a reduced ability to encode olfactory information and a reduced volume of the olfactory bulb. While similar processes seem to occur in healthy individuals experiencing depressive states, they have not been observed in BPD or SAD patients. However, in order to conclude that the reduced olfactory sensitivity is directly linked to depression, it is suggested that studies should implement control measures of cognitive performances or perceptual abilities in other stimulus modalities. It is concluded that the reduced olfactory performance in MDD patients seems to be disorder-, modality-, and test-specific, and that the application of an appropriate olfactory and cognitive test-battery might be highly useful in the differential diagnosis of MDD. PMID:24570666

  20. Recent Trend in Development of Olfactory Displays

    NASA Astrophysics Data System (ADS)

    Yanagida, Yasuyuki

    An olfactory display is a device that generates scented air with desired concentration of aroma, and delivers it to the user's olfactory organ. In this article, the nature of olfaction is briefly described from the view point of how to configure olfactory displays. Next, component technologies to compose olfactory displays, i.e., making scents and delivering scents, are categorized. Several existing olfactory display systems are introduced to show the current status of research and development of olfactory displays.

  1. Surface coatings of ZnO nanoparticles mitigate differentially a host of transcriptional, protein and signalling responses in primary human olfactory cells

    PubMed Central

    2013-01-01

    Background Inhaled nanoparticles have been reported in some instances to translocate from the nostril to the olfactory bulb in exposed rats. In close proximity to the olfactory bulb is the olfactory mucosa, within which resides a niche of multipotent cells. Cells isolated from this area may provide a relevant in vitro system to investigate potential effects of workplace exposure to inhaled zinc oxide nanoparticles. Methods Four types of commercially-available zinc oxide (ZnO) nanoparticles, two coated and two uncoated, were examined for their effects on primary human cells cultured from the olfactory mucosa. Human olfactory neurosphere-derived (hONS) cells from healthy adult donors were analyzed for modulation of cytokine levels, activation of intracellular signalling pathways, changes in gene-expression patterns across the whole genome, and compromised cellular function over a 24 h period following exposure to the nanoparticles suspended in cell culture medium. Results ZnO nanoparticle toxicity in hONS cells was mediated through a battery of mechanisms largely related to cell stress, inflammatory response and apoptosis, but not activation of mechanisms that repair damaged DNA. Surface coatings on the ZnO nanoparticles mitigated these cellular responses to varying degrees. Conclusions The results indicate that care should be taken in the workplace to minimize generation of, and exposure to, aerosols of uncoated ZnO nanoparticles, given the adverse responses reported here using multipotent cells derived from the olfactory mucosa. PMID:24144420

  2. REGULATOR OF BULB BIOGENESIS1 (RBB1) Is Involved in Vacuole Bulb Formation in Arabidopsis.

    PubMed

    Han, Sang Won; Alonso, Jose M; Rojas-Pierce, Marcela

    2015-01-01

    Vacuoles are dynamic compartments with constant fluctuations and transient structures such as trans-vacuolar strands and bulbs. Bulbs are highly dynamic spherical structures inside vacuoles that are formed by multiple layers of membranes and are continuous with the main tonoplast. We recently carried out a screen for mutants with abnormal trafficking to the vacuole or aberrant vacuole morphology. We characterized regulator of bulb biogenesis1-1 (rbb1-1), a mutant in Arabidopsis that contains increased numbers of bulbs when compared to the parental control. rbb1-1 mutants also contain fewer transvacuolar strands than the parental control, and we propose the hypothesis that the formation of transvacuolar strands and bulbs is functionally related. We propose that the bulbs may function transiently to accommodate membranes and proteins when transvacuolar strands fail to elongate. We show that RBB1 corresponds to a very large protein of unknown function that is specific to plants, is present in the cytosol, and may associate with cellular membranes. RBB1 is involved in the regulation of vacuole morphology and may be involved in the establishment or stability of trans-vacuolar strands and bulbs.

  3. Imaging evolutionarily conserved neural networks: preferential activation of the olfactory system by food-related odor.

    PubMed

    Kulkarni, Praveen; Stolberg, Tara; Sullivanjr, J M; Ferris, Craig F

    2012-04-21

    Rodents routinely forge and rely on hippocampal-dependent spatial memory to guide them to sources of caloric rich food in their environment. Has evolution affected the olfactory system and its connections to the hippocampus and limbic cortex, so rodents have an innate sensitivity to energy rich food and their location? To test this notion, we used functional magnetic resonance imaging in awake rats to observe changes in brain activity in response to four odors: benzaldehyde (almond odor), isoamyl acetate (banana odor), methyl benzoate (rosy odor), and limonene (citrus odor). We chose the almond odor because nuts are high in calories and would be expected to convey greater valance as compared to the other odors. Moreover, the standard food chow is devoid of nuts, so laboratory bred rats would not have any previous exposure to this food. Activation maps derived from computational analysis using a 3D segmented rat MRI atlas were dramatically different between odors. Animals exposed to banana, rosy and citrus odors showed modest activation of the primary olfactory system, hippocampus and limbic cortex. However, animals exposed to almond showed a robust increase in brain activity in the primary olfactory system particularly the main olfactory bulb, anterior olfactory nucleus and tenia tecta. The most significant difference in brain activation between odors was observed in the hippocampus and limbic cortex. These findings show that fMRI can be used to identify neural circuits that have an innate sensitivity to environmental stimuli that may help in an animal's survival. PMID:22343130

  4. Avian olfactory receptor gene repertoires: evidence for a well-developed sense of smell in birds?

    PubMed

    Steiger, Silke S; Fidler, Andrew E; Valcu, Mihai; Kempenaers, Bart

    2008-10-22

    Among vertebrates, the sense of smell is mediated by olfactory receptors (ORs) expressed in sensory neurons within the olfactory epithelium. Comparative genomic studies suggest that the olfactory acuity of mammalian species correlates positively with both the total number and the proportion of functional OR genes encoded in their genomes. In contrast to mammals, avian olfaction is poorly understood, with birds widely regarded as relying primarily on visual and auditory inputs. Here, we show that in nine bird species from seven orders (blue tit, Cyanistes caeruleus; black coucal, Centropus grillii; brown kiwi, Apteryx australis; canary, Serinus canaria; galah, Eolophus roseicapillus; red jungle fowl, Gallus gallus; kakapo, Strigops habroptilus; mallard, Anas platyrhynchos; snow petrel, Pagodroma nivea), the majority of amplified OR sequences are predicted to be from potentially functional genes. This finding is somewhat surprising as one previous report suggested that the majority of OR genes in an avian (red jungle fowl) genomic sequence are non-functional pseudogenes. We also show that it is not the estimated proportion of potentially functional OR genes, but rather the estimated total number of OR genes that correlates positively with relative olfactory bulb size, an anatomical correlate of olfactory capability. We further demonstrate that all the nine bird genomes examined encode OR genes belonging to a large gene clade, termed gamma-c, the expansion of which appears to be a shared characteristic of class Aves. In summary, our findings suggest that olfaction in birds may be a more important sense than generally believed. PMID:18628122

  5. Loss of NEIL1 causes defects in olfactory function in mice.

    PubMed

    Canugovi, Chandrika; Misiak, Magdalena; Scheibye-Knudsen, Morten; Croteau, Deborah L; Mattson, Mark P; Bohr, Vilhelm A

    2015-02-01

    Oxidative DNA damage accumulation has been implicated in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. The base excision repair pathway is a primary responder to oxidative DNA damage. Effects of loss of base excision repair on normal brain function is a relatively nascent area of research that needs further exploration for better understanding of related brain diseases. Recently, we found that loss of a versatile DNA glycosylase endonuclease 8-like 1 (NEIL1) causes deficits in spatial memory retention using the Morris water maze test. Furthermore, we found that there is a significant loss of NEIL1 enzyme levels and its activity in postmortem Alzheimer's disease brains. Based on the Allen Brain Atlas in situ hybridization data, the expression levels of Neil1 messenger RNA are higher in the olfactory bulb compared with other areas of the brain. Olfaction in mice is a central brain function that involves many central nervous system pathways. Here, we studied the effect of complete loss of Neil1 gene on olfactory function. We explored olfactory function in mice with 3 different behavioral tests namely, olfactory sensitivity, performance, and buried food tests. Neil1(-/-) mice performed poorly compared with wild-type mice in all 3 tests. Our data indicate that loss of Neil1 causes olfactory function deficits supporting our previous findings and that normal brain function requires robust DNA repair. PMID:25448603

  6. Brain lesion-pattern analysis in patients with olfactory dysfunctions following head trauma.

    PubMed

    Lötsch, Jörn; Ultsch, Alfred; Eckhardt, Maren; Huart, Caroline; Rombaux, Philippe; Hummel, Thomas

    2016-01-01

    The presence of cerebral lesions in patients with neurosensory alterations provides a unique window into brain function. Using a fuzzy logic based combination of morphological information about 27 olfactory-eloquent brain regions acquired with four different brain imaging techniques, patterns of brain damage were analyzed in 127 patients who displayed anosmia, i.e., complete loss of the sense of smell (n = 81), or other and mechanistically still incompletely understood olfactory dysfunctions including parosmia, i.e., distorted perceptions of olfactory stimuli (n = 50), or phantosmia, i.e., olfactory hallucinations (n = 22). A higher prevalence of parosmia, and as a tendency also phantosmia, was observed in subjects with medium overall brain damage. Further analysis showed a lower frequency of lesions in the right temporal lobe in patients with parosmia than in patients without parosmia. This negative direction of the differences was unique for parosmia. In anosmia, and also in phantosmia, lesions were more frequent in patients displaying the respective symptoms than in those without these dysfunctions. In anosmic patients, lesions in the right olfactory bulb region were much more frequent than in patients with preserved sense of smell, whereas a higher frequency of carriers of lesions in the left frontal lobe was observed for phantosmia. We conclude that anosmia, and phantosmia, are the result of lost function in relevant brain areas whereas parosmia is more complex, requiring damaged and intact brain regions at the same time. PMID:26937377

  7. Brain lesion-pattern analysis in patients with olfactory dysfunctions following head trauma

    PubMed Central

    Lötsch, Jörn; Ultsch, Alfred; Eckhardt, Maren; Huart, Caroline; Rombaux, Philippe; Hummel, Thomas

    2016-01-01

    The presence of cerebral lesions in patients with neurosensory alterations provides a unique window into brain function. Using a fuzzy logic based combination of morphological information about 27 olfactory-eloquent brain regions acquired with four different brain imaging techniques, patterns of brain damage were analyzed in 127 patients who displayed anosmia, i.e., complete loss of the sense of smell (n = 81), or other and mechanistically still incompletely understood olfactory dysfunctions including parosmia, i.e., distorted perceptions of olfactory stimuli (n = 50), or phantosmia, i.e., olfactory hallucinations (n = 22). A higher prevalence of parosmia, and as a tendency also phantosmia, was observed in subjects with medium overall brain damage. Further analysis showed a lower frequency of lesions in the right temporal lobe in patients with parosmia than in patients without parosmia. This negative direction of the differences was unique for parosmia. In anosmia, and also in phantosmia, lesions were more frequent in patients displaying the respective symptoms than in those without these dysfunctions. In anosmic patients, lesions in the right olfactory bulb region were much more frequent than in patients with preserved sense of smell, whereas a higher frequency of carriers of lesions in the left frontal lobe was observed for phantosmia. We conclude that anosmia, and phantosmia, are the result of lost function in relevant brain areas whereas parosmia is more complex, requiring damaged and intact brain regions at the same time. PMID:26937377

  8. Differential responses to branched and unsaturated aliphatic hydrocarbons in the rat olfactory system

    PubMed Central

    Ho, Sabrina L.; Johnson, Brett A.; Chen, Andrew L.; Leon, Michael

    2008-01-01

    In an effort to understand mammalian olfactory processing, we have been describing the responses to systematically different odorants in the glomerular layer of the main olfactory bulb of rats. Previously, we have demonstrated chemotopically organized and distinct olfactory responses to a homologous series of straight-chained alkanes that consisted of purely hydrocarbon structures, indicating that hydrocarbon chains could serve as molecular features in the combinatorial coding of odorant information. To better understand the processing of hydrocarbon odorants, we now have examined responses to other types of chemical changes in this kind of molecules, namely branching and carbon-carbon bond saturation. To this end, we used the [14C]2-deoxyglucose method to determine glomerular responses to a group of eight-carbon branched alkane isomers, unsaturated octenes (double-bonded), and octynes (triple-bonded). In contrast to the differential responses we observed previously for straight-chained alkanes of differing carbon number, the rat olfactory system was not particularly sensitive to these variations in branching and bond saturation. This result was unexpected, given the distinct molecular conformations and property profiles of the odorants. The similarity in activity patterns was paralleled by a similarity in spontaneous perceptual responses measured using a habituation assay. These results demonstrate again the functional relationship between bulbar activity patterns and odor perception. The results further suggest that the olfactory system does not respond equally to all aspects of odorant chemistry, functioning as a specific, rather than a general chemical analysis system. PMID:17029262

  9. Effects of inhalation of cadmium on the rat olfactory system: behavior and morphology.

    PubMed

    Sun, T J; Miller, M L; Hastings, L

    1996-01-01

    To investigate the effects of cadmium on olfaction, two separate studies were conducted in which male adult rats were exposed to CdO, via inhalation, for 5 h per day, 5 days a week for 20 weeks. Target exposure values of 250 and 500 micrograms/m3 were measured at 200 and 325 micrograms/m3 for the low concentration in two experiments, and 550 and 660 micrograms/m3 for the high concentration. Prior to exposure, olfactory thresholds were obtained using a conditioned suppression technique. After 20 weeks of cadmium exposure, there was no evidence of anosmia in any of the rats nor were there any significant changes observed in olfactory thresholds. Although olfaction was not impaired, cadmium levels in the olfactory bulbs of exposed rats were significantly elevated compared to controls. Cardiac and respiratory histopathology were observed at all exposure levels, but there was no evidence of nasal pathology related to exposure to cadmium. Failure of cadmium to produce olfactory dysfunction may be due to the protective effects of metallothionein and/or to the highly resilient nature of the rodent olfactory system.

  10. Loss of NEIL1 causes defects in olfactory function in mice.

    PubMed

    Canugovi, Chandrika; Misiak, Magdalena; Scheibye-Knudsen, Morten; Croteau, Deborah L; Mattson, Mark P; Bohr, Vilhelm A

    2015-02-01

    Oxidative DNA damage accumulation has been implicated in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. The base excision repair pathway is a primary responder to oxidative DNA damage. Effects of loss of base excision repair on normal brain function is a relatively nascent area of research that needs further exploration for better understanding of related brain diseases. Recently, we found that loss of a versatile DNA glycosylase endonuclease 8-like 1 (NEIL1) causes deficits in spatial memory retention using the Morris water maze test. Furthermore, we found that there is a significant loss of NEIL1 enzyme levels and its activity in postmortem Alzheimer's disease brains. Based on the Allen Brain Atlas in situ hybridization data, the expression levels of Neil1 messenger RNA are higher in the olfactory bulb compared with other areas of the brain. Olfaction in mice is a central brain function that involves many central nervous system pathways. Here, we studied the effect of complete loss of Neil1 gene on olfactory function. We explored olfactory function in mice with 3 different behavioral tests namely, olfactory sensitivity, performance, and buried food tests. Neil1(-/-) mice performed poorly compared with wild-type mice in all 3 tests. Our data indicate that loss of Neil1 causes olfactory function deficits supporting our previous findings and that normal brain function requires robust DNA repair.

  11. A higher oxidative status accelerates senescence and aggravates age-dependent disorders in SAMP strains of mice.

    PubMed

    Hosokawa, Masanori

    2002-11-01

    The SAM strain of mice is actually a group of related inbred strains consisting of series of SAMP (accelerated senescence-prone, short-lived) and SAMR (accelerated senescence-resistant, longer-lived) strains. Comparing with the SAMR strains, the SAMP strains of mice show a more accelerated senescence process, shorter lifespan, and an earlier onset and more rapid progress of age-associated pathological phenotypes similar to several geriatric disorders observed in humans, including senile osteoporosis, degenerative joint disease, age-related deficits in learning and memory, olfactory bulb and forebrain atrophy, presbycusis and retinal atrophy, senile amyloidosis, immunosenescence, senile lungs, and diffuse medial thickening of the aorta. The higher oxidative stress observed in the SAMP strains of mice are partly caused by mitochondrial dysfunction, and may be one cause of the senescence acceleration and age-dependent alterations in cell structure and function, including neuronal cell degeneration. This senescence acceleration is also observed during senescence/crisis in cultures of isolated fibroblast-like cells from SAMP strains of mice, and was associated with a hyperoxidative status. These observations suggest that the SAM strains are useful tools in the attempt to understand the mechanisms of age-dependent degeneration of cells and tissues, and their aggravation, and to develop clinical interventions. PMID:12470893

  12. Computational Biology of Olfactory Receptors

    PubMed Central

    Crasto, Chiquito J.

    2011-01-01

    Olfactory receptors, in addition to being involved in first step of the physiological processes that leads to olfaction, occupy an important place in mammalian genomes. ORs constitute super families in these genomes. Elucidating ol-factory receptor function at a molecular level can be aided by a computationally derived structure and an understanding of its interactions with odor molecules. Experimental functional analyses of olfactory receptors in conjunction with computational studies serve to validate findings and generate hypotheses. We present here a review of the research efforts in: creating computational models of olfactory receptors, identifying binding strategies for these receptors with odorant molecules, performing medium to long range simulation studies of odor ligands in the receptor binding region, and identifying amino acid positions within the receptor that are responsible for ligand-binding and olfactory receptor activation. Written as a primer and a teaching tool, this review will help researchers extend the methodologies described herein to other GPCRs. PMID:21984880

  13. Role of Rb during Neurogenesis and Axonal Guidance in the Developing Olfactory System

    PubMed Central

    Jaafar, Carine; Omais, Saad; Al Lafi, Sawsan; El Jamal, Nadim; Noubani, Mohammad; Skaf, Larissa; Ghanem, Noël

    2016-01-01

    The Retinoblastoma protein, Rb, was shown to regulate distinct aspects of neurogenesis in the embryonic and adult brain besides its primary role in cell cycle control. It is still unknown, however, whether Rb is required for tissue morphogenesis and the establishment of synaptic connections between adjacent tissues during development. We have investigated here the role of Rb during development of the olfactory system (OS), which heavily relies on reciprocal interactions between the olfactory epithelium (OE) and the olfactory bulb (OB). We show that mice carrying a telencephalic-specific deletion of Rb display several neurogenic defects in the OS during late development. In the OE, loss of Rb leads to ectopic proliferation of late-born progenitors (Tuj-1+), abnormal radial migration and terminal maturation of olfactory sensory neurons (OSNs). In the OB, deletion of Rb causes severe lamination defects with loss of clear boundaries between distinct layers. Importantly, starting around E15.5 when OB glomerulogenesis is initiated, many OSNs axons that project along the olfactory nerve layer (ONL) fail to properly innervate the nascent bulb, thus resulting in partial loss of connectivity between OE-OB and gradual neuronal degeneration in both tissues peaking at birth. This deficiency correlates with deregulated expressions of two key chemo-repellant molecules, Robo2/Slit1 and Nrp2/Sema3F that control the formation of dorsal-ventral topographic map of OSNs connections with OB glomeruli. This study highlights a critical requirement for Rb during neurogenesis and the establishment of proper synaptic connections inside the OS during development. PMID:27667971

  14. Role of Rb during Neurogenesis and Axonal Guidance in the Developing Olfactory System.

    PubMed

    Jaafar, Carine; Omais, Saad; Al Lafi, Sawsan; El Jamal, Nadim; Noubani, Mohammad; Skaf, Larissa; Ghanem, Noël

    2016-01-01

    The Retinoblastoma protein, Rb, was shown to regulate distinct aspects of neurogenesis in the embryonic and adult brain besides its primary role in cell cycle control. It is still unknown, however, whether Rb is required for tissue morphogenesis and the establishment of synaptic connections between adjacent tissues during development. We have investigated here the role of Rb during development of the olfactory system (OS), which heavily relies on reciprocal interactions between the olfactory epithelium (OE) and the olfactory bulb (OB). We show that mice carrying a telencephalic-specific deletion of Rb display several neurogenic defects in the OS during late development. In the OE, loss of Rb leads to ectopic proliferation of late-born progenitors (Tuj-1+), abnormal radial migration and terminal maturation of olfactory sensory neurons (OSNs). In the OB, deletion of Rb causes severe lamination defects with loss of clear boundaries between distinct layers. Importantly, starting around E15.5 when OB glomerulogenesis is initiated, many OSNs axons that project along the olfactory nerve layer (ONL) fail to properly innervate the nascent bulb, thus resulting in partial loss of connectivity between OE-OB and gradual neuronal degeneration in both tissues peaking at birth. This deficiency correlates with deregulated expressions of two key chemo-repellant molecules, Robo2/Slit1 and Nrp2/Sema3F that control the formation of dorsal-ventral topographic map of OSNs connections with OB glomeruli. This study highlights a critical requirement for Rb during neurogenesis and the establishment of proper synaptic connections inside the OS during development. PMID:27667971

  15. Role of Rb during Neurogenesis and Axonal Guidance in the Developing Olfactory System

    PubMed Central

    Jaafar, Carine; Omais, Saad; Al Lafi, Sawsan; El Jamal, Nadim; Noubani, Mohammad; Skaf, Larissa; Ghanem, Noël

    2016-01-01

    The Retinoblastoma protein, Rb, was shown to regulate distinct aspects of neurogenesis in the embryonic and adult brain besides its primary role in cell cycle control. It is still unknown, however, whether Rb is required for tissue morphogenesis and the establishment of synaptic connections between adjacent tissues during development. We have investigated here the role of Rb during development of the olfactory system (OS), which heavily relies on reciprocal interactions between the olfactory epithelium (OE) and the olfactory bulb (OB). We show that mice carrying a telencephalic-specific deletion of Rb display several neurogenic defects in the OS during late development. In the OE, loss of Rb leads to ectopic proliferation of late-born progenitors (Tuj-1+), abnormal radial migration and terminal maturation of olfactory sensory neurons (OSNs). In the OB, deletion of Rb causes severe lamination defects with loss of clear boundaries between distinct layers. Importantly, starting around E15.5 when OB glomerulogenesis is initiated, many OSNs axons that project along the olfactory nerve layer (ONL) fail to properly innervate the nascent bulb, thus resulting in partial loss of connectivity between OE-OB and gradual neuronal degeneration in both tissues peaking at birth. This deficiency correlates with deregulated expressions of two key chemo-repellant molecules, Robo2/Slit1 and Nrp2/Sema3F that control the formation of dorsal-ventral topographic map of OSNs connections with OB glomeruli. This study highlights a critical requirement for Rb during neurogenesis and the establishment of proper synaptic connections inside the OS during development.

  16. Demonstrating Absorption Spectra Using Commercially Available Incandescent Light Bulbs

    NASA Astrophysics Data System (ADS)

    Birriel, Jennifer J.

    In introductory astronomy courses, I typically introduce the three types of spectra: continuous, absorption line, and emission line. It is standard practice to use an ordinary incandescent light bulb to demonstrate the production of a continuous spectrum, and gas discharge tubes to demonstrate the production of an emission line spectrum. The concept of an absorption spectrum is more difficult for students to grasp. A variety of commercially available light bulbs can be used to demonstrate absorption spectra. Here I discuss the use of specialty incandescent light bulbs to demonstrate the phenomenon of absorption of the continuous spectrum produced by a hot tungsten filament. The bulbs examined include the GE Reveal bulb, yellow anti-insect lights, colored party bulbs, and an incandescent "black light" bulb. The bulbs can be used in a lecture or laboratory setting.

  17. Hypothalamic and olfactory control of sexual behavior and partner preference in male rats.

    PubMed

    Edwards, D A; Walter, B; Liang, P

    1996-11-01

    Sexually active male rats prefer a sexually receptive female to a nonreceptive female, and partner-preference tests provide one way of studying sexual motivation. Surgical deafferentation of the olfactory bulbs from all the known chemosensory systems of the nasal septum renders rats anosmic. In Experiment 1, we show that, although bulb deafferentation of male rats decreases some aspects of sexual performance,