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Sample records for olfactory bulb accelerates

  1. Adult Olfactory Bulb Neurogenesis.

    PubMed

    Lledo, Pierre-Marie; Valley, Matt

    2016-01-01

    Most organisms use their olfactory system to detect and analyze chemical cues from the external world to guide essential behaviors. From worms to vertebrates, chemicals are detected by odorant receptors expressed by olfactory sensory neurons, which in vertebrates send an axon to the primary processing center called the olfactory bulb (OB). Within the OB, sensory neurons form excitatory synapses with projection neurons and with inhibitory interneurons. Thus, because of complex synaptic interactions, the output of a given projection neuron is determined not only by the sensory input, but also by the activity of local inhibitory interneurons that are regenerated throughout life in the process of adult neurogenesis. Herein, we discuss how it is optimized and why. PMID:27235474

  2. 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

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

    PubMed

    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

  4. Neuronal organization of olfactory bulb circuits

    PubMed Central

    Nagayama, Shin; Homma, Ryota; Imamura, Fumiaki

    2014-01-01

    Olfactory sensory neurons extend their axons solely to the olfactory bulb, which is dedicated to odor information processing. The olfactory bulb is divided into multiple layers, with different types of neurons found in each of the layers. Therefore, neurons in the olfactory bulb have conventionally been categorized based on the layers in which their cell bodies are found; namely, juxtaglomerular cells in the glomerular layer, tufted cells in the external plexiform layer, mitral cells in the mitral cell layer, and granule cells in the granule cell layer. More recently, numerous studies have revealed the heterogeneous nature of each of these cell types, allowing them to be further divided into subclasses based on differences in morphological, molecular, and electrophysiological properties. In addition, technical developments and advances have resulted in an increasing number of studies regarding cell types other than the conventionally categorized ones described above, including short-axon cells and adult-generated interneurons. Thus, the expanding diversity of cells in the olfactory bulb is now being acknowledged. However, our current understanding of olfactory bulb neuronal circuits is mostly based on the conventional and simplest classification of cell types. Few studies have taken neuronal diversity into account for understanding the function of the neuronal circuits in this region of the brain. This oversight may contribute to the roadblocks in developing more precise and accurate models of olfactory neuronal networks. The purpose of this review is therefore to discuss the expanse of existing work on neuronal diversity in the olfactory bulb up to this point, so as to provide an overall picture of the olfactory bulb circuit. PMID:25232305

  5. Cortical feedback control of olfactory bulb circuits.

    PubMed

    Boyd, Alison M; Sturgill, James F; Poo, Cindy; Isaacson, Jeffry S

    2012-12-20

    Olfactory cortex pyramidal cells integrate sensory input from olfactory bulb mitral and tufted (M/T) cells and project axons back to the bulb. However, the impact of cortical feedback projections on olfactory bulb circuits is unclear. Here, we selectively express channelrhodopsin-2 in olfactory cortex pyramidal cells and show that cortical feedback projections excite diverse populations of bulb interneurons. Activation of cortical fibers directly excites GABAergic granule cells, which in turn inhibit M/T cells. However, we show that cortical inputs preferentially target short axon cells that drive feedforward inhibition of granule cells. In vivo, activation of olfactory cortex that only weakly affects spontaneous M/T cell firing strongly gates odor-evoked M/T cell responses: cortical activity suppresses odor-evoked excitation and enhances odor-evoked inhibition. Together, these results indicate that although cortical projections have diverse actions on olfactory bulb microcircuits, the net effect of cortical feedback on M/T cells is an amplification of odor-evoked inhibition. PMID:23259951

  6. 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

  7. 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…

  8. Modeling Olfactory Bulb Evolution through Primate Phylogeny

    PubMed Central

    Heritage, Steven

    2014-01-01

    Adaptive characterizations of primates have usually included a reduction in olfactory sensitivity. However, this inference of derivation and directionality assumes an ancestral state of olfaction, usually by comparison to a group of extant non-primate mammals. Thus, the accuracy of the inference depends on the assumed ancestral state. Here I present a phylogenetic model of continuous trait evolution that reconstructs olfactory bulb volumes for ancestral nodes of primates and mammal outgroups. Parent-daughter comparisons suggest that, relative to the ancestral euarchontan, the crown-primate node is plesiomorphic and that derived reduction in olfactory sensitivity is an attribute of the haplorhine lineage. The model also suggests a derived increase in olfactory sensitivity at the strepsirrhine node. This oppositional diversification of the strepsirrhine and haplorhine lineages from an intermediate and non-derived ancestor is inconsistent with a characterization of graded reduction through primate evolution. PMID:25426851

  9. 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…

  10. 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

  11. 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

  12. 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

  13. 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. PMID:25995474

  14. 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…

  15. Long-term recording of olfactory and vomeronasal stimulant-induced waves from the turtle main olfactory bulb and accessory olfactory bulb.

    PubMed

    Kashiwayanagi, M; Taniguchi, M; Shoji, T; Kurihara, K

    1997-08-01

    Recording of stimulant-induced waves (bulbar responses) from the main olfactory bulb is a useful tool for measuring quantitative stable olfactory responses. There is a good relationship between the olfactory bulbar response, olfactory nerve response and electroolfactogram (EOG), suggesting that the bulbar response reflects events in receptor cells. The modern whole-cell recording technique offers direct information on olfactory transduction in single cells, but it requires long experimental periods and many animals. On the other hand, analysis of bulbar responses provides useful information and requires the use of few animals. For example, we found that cAMP-increasing and IP3-increasing odorants were not distinctly received by the turtle olfactory organ by measuring olfactory bulbar responses and analyzed with a multidimensional scaling from about 60 animals. However, to record similar odor responses from isolated turtle olfactory neurons, at least 200 animals would be necessary. Bulbar responses are recorded with electrodes implanted into or located on the main olfactory bulb. When electrodes are located on the olfactory bulb surface, it is possible to record stable responses over a period of 3 days. These methods were applied successfully to the accessory olfactory bulb. In this paper, we describe the protocols used for recording of the stimulant-induced waves from the main and accessory olfactory bulb. PMID:9385067

  16. 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

  17. 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

  18. Netrin/DCC signaling guides olfactory sensory axons to their correct location in the olfactory bulb

    PubMed Central

    Lakhina, Vanisha; Marcaccio, Christina L.; Shao, Xin; Lush, Mark E.; Jain, Roshan A.; Fujimoto, Esther; Bonkowsky, Joshua L.; Granato, Michael; Raper, Jonathan A.

    2012-01-01

    Olfactory sensory neurons expressing particular olfactory receptors project to specific reproducible locations within the bulb. The axonal guidance cues that organize this precise projection pattern are only beginning to be identified. To aid in their identification and characterization, we generated a transgenic zebrafish line, OR111-7:IRES:Gal4, in which a small subset of olfactory sensory neurons is labeled. Most sensory neurons expressing the OR111-7 transgene project to a specific location within the bulb, the central zone protoglomerulus, while a smaller number project to the LG1 protoglomerulus. Inhibiting netrin/DCC signaling perturbs the ability of OR111-7 expressing axons to enter the olfactory bulb and alters their patterns of termination within the bulb. The netrin receptor DCC is expressed in olfactory sensory neurons around the time that they elaborate their axons, netrin1a is expressed near the medial-most margin of the olfactory bulb, and netrin1b is expressed within the ventral region of the bulb. Loss of netrin/DCC signaling components causes some OR111-7 expressing sensory axons to wander posteriorly after exiting the olfactory pit, away from netrin expressing areas in the bulb. OR111-7 expressing axons that enter the bulb target the central zone less precisely than normal, spreading away from netrin expressing regions. These pathfinding errors can be corrected by the re-expression of DCC within OR111-7 transgene expressing neurons in DCC morphant embryos. These findings implicate netrins as the only known attractants for olfactory sensory neurons, first drawing OR111-7 expressing axons into the bulb and then into the ventromedially positioned central zone protoglomerulus. PMID:22457493

  19. 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

  20. Synaptic clusters function as odor operators in the olfactory bulb

    PubMed Central

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

    2015-01-01

    How the olfactory bulb organizes and processes odor inputs through fundamental operations of its microcircuits is largely unknown. To gain new insight we focus on odor-activated synaptic clusters related to individual glomeruli, which we call glomerular units. Using a 3D model of mitral and granule cell interactions supported by experimental findings, combined with a matrix-based representation of glomerular operations, we identify the mechanisms for forming one or more glomerular units in response to a given odor, how and to what extent the glomerular units interfere or interact with each other during learning, their computational role within the olfactory bulb microcircuit, and how their actions can be formalized into a theoretical framework in which the olfactory bulb can be considered to contain “odor operators” unique to each individual. The results provide new and specific theoretical and experimentally testable predictions. PMID:26100895

  1. Olfactory deprivation increases dopamine D2 receptor density in the rat olfactory bulb

    SciTech Connect

    Guthrie, K.M.; Pullara, J.M.; Marshall, J.F.; Leon, M. )

    1991-05-01

    Unilateral olfactory deprivation during postnatal development results in significant anatomical and neurochemical changes in the deprived olfactory bulb. Perhaps the most dramatic neurochemical change is the loss of dopaminergic expression by neurons of the glomerular region. The authors describe here the effects of early olfactory deprivation on other elements of the bulb dopaminergic system, namely the dopamine receptors of the olfactory bulb. Rat pups had a single naris occluded on postnatal day 2 (PN2). On PN20 or PN60, animals were sacrificed and the bulbs were examined for catecholamine levels or D2 and D1 dopamine receptor binding. Receptor densities were quantified by in vitro autoradiography using the tritiated antagonists spiperone (D2) and SCH23390 (D1). Dopamine uptake sites were similarly examined using tritiated mazindol. No significant specific labeling of D1 or mazindol sites was observed in the olfactory bulbs of control or experimental animals at either age. Normal animals displayed prominent labeling of D2 sites in the glomerular and nerve layers. After 60 days of deprivation, deprived bulbs exhibited an average increase in D2 receptor density of 32%. As determined by Scatchard analysis, the mean values for Kd and Bmax were 0.134 nM and 293 fmol/mg protein in normal bulbs, and 0.136 nM and 403 fmol/mg protein in deprived bulbs. The results suggest that, as in the neostriatum, dopamine depletion in the olfactory bulb leads to an upregulation of D2 receptor sites. This change may represent an attempt by the system to adapt neurochemically to reduced dopaminergic activity and thereby maintain bulb function.

  2. Reversible Deafferentation of the Adult Zebrafish Olfactory Bulb Affects Glomerular Distribution and Olfactory-Mediated Behavior

    PubMed Central

    Paskin, Taylor R.; Byrd-Jacobs, Christine A.

    2012-01-01

    The olfactory system is a useful model for studying central nervous system recovery from damage due to its neuroplasticity. We recently developed a novel method of deafferentation by repeated exposure of Triton X-100 to the olfactory organ of adult zebrafish. This long-term, reversible method of deafferentation allows both degeneration and regeneration to be observed in the olfactory bulb. The aim of the present study is to examine olfactory bulb innervation, glomerular patterns, and olfactory-mediated behavior with repeated Triton X-100 treatment and the potential for recovery following cessation of treatment. Olfactory bulbs of control, chronic-treated, and recovery animals were examined for the presence or absence of glomeruli that have been identified in the zebrafish glomerular map. Following chronic treatment, the number of glomeruli was dramatically reduced; however, partial innervation remained in the lateral region of the bulb. When animals were given time to recover, complete glomerular distribution returned. A behavioral assay was developed to determine if innervation remaining correlated with behavior of the fish. Chronic-treated fish did not respond to odorants involved with social behavior but continued to react to odorants that mediate feeding behavior. Following recovery, responses to odorants involved with social behavior returned. The morphological and behavioral effects of chronic Triton X-100 treatment in the olfactory system suggest there may be differential susceptibility or resistance to external damage in a subset of sensory neurons. The results of this study demonstrate the remarkable regenerative ability of the olfactory system following extensive and long-term injury. PMID:22963994

  3. Reversible deafferentation of the adult zebrafish olfactory bulb affects glomerular distribution and olfactory-mediated behavior.

    PubMed

    Paskin, Taylor R; Byrd-Jacobs, Christine A

    2012-12-01

    The olfactory system is a useful model for studying central nervous system recovery from damage due to its neuroplasticity. We recently developed a novel method of deafferentation by repeated exposure of Triton X-100 to the olfactory organ of adult zebrafish. This long-term, reversible method of deafferentation allows both degeneration and regeneration to be observed in the olfactory bulb. The aim of the present study is to examine olfactory bulb innervation, glomerular patterns, and olfactory-mediated behavior with repeated Triton X-100 treatment and the potential for recovery following cessation of treatment. Olfactory bulbs of control, chronic-treated, and recovery animals were examined for the presence or absence of glomeruli that have been identified in the zebrafish glomerular map. Following chronic treatment, the number of glomeruli was dramatically reduced; however, partial innervation remained in the lateral region of the bulb. When animals were given time to recover, complete glomerular distribution returned. A behavioral assay was developed to determine if innervation remaining correlated with behavior of the fish. Chronic-treated fish did not respond to odorants involved with social behavior but continued to react to odorants that mediate feeding behavior. Following recovery, responses to odorants involved with social behavior returned. The morphological and behavioral effects of chronic Triton X-100 treatment in the olfactory system suggest there may be differential susceptibility or resistance to external damage in a subset of sensory neurons. The results of this study demonstrate the remarkable regenerative ability of the olfactory system following extensive and long-term injury. PMID:22963994

  4. THE DISTINCT TEMPORAL ORIGINS OF OLFACTORY BULB INTERNEURON SUBTYPES

    PubMed Central

    Batista-Brito, Renata; Close, Jennie; Machold, Robert; Ekker, Mark; Fishell, Gord

    2008-01-01

    Olfactory bulb (OB) interneurons are a heterogeneous population produced beginning in embryogenesis and continuing through adulthood. Understanding how this diversity arises will provide insight into how olfactory bulb microcircuitry is established as well as adult neurogenesis. Specific spatial domains have been shown to contribute specific interneuron subtypes. However, the temporal profile by which OB interneuron subtypes are produced is unknown. Using inducible genetic fate mapping of Dlx1/2 precursors, we analyzed the production of seven OB interneuron subtypes and find that the generation of each subpopulation has a unique temporal signature. Within the glomerular layer, while the production of TH-positive interneurons is maximal during early embryogenesis, it decreases thereafter. By contrast, the generation of CB interneurons is maximal during late embryogenesis and declines postnatally, while CR cell production is low during embryogenesis and increases postnatally. PV interneurons within the external plexiform layer are produced only perinatally, while the generation of 5T4-positive granule cells in the mitral cell layer does not change significantly over time. CR-positive granule cells are not produced at early embryonic timepoints, but constitute a large percentage of the granule cells born after birth. Blanes cells by contrast are produced in greatest number during embryogenesis. Taken together we provide the first comprehensive analysis of the temporal generation of olfactory bulb interneuron subtypes and demonstrate that the timing by which these populations are produced is tightly orchestrated. PMID:18400896

  5. Comparative morphology of the accessory olfactory bulb in bats.

    PubMed Central

    Frahm, H D; Bhatnagar, K P

    1980-01-01

    Bouin-perfused brains of 148 bats (76 species, 48 genera, 8 families) were examined in serial sections for the presence of an accessory olfactory bulb. A moderate to well developed AOB was identified in 26 species. However, absence of an AOB in a particular species does not preclude its presence in some other species of that genus. Descriptions and measurements of the AOBs of each species are reported. The unmyelinated vomeronasal nerve enters the bulb medially and posteriorly. The glomeruli, variable in diameter, appear better circumscribed than previously described. Mitral cells often form thick layers, up to five cells deep, which sometimes reach the dorsolateral surface of the bulb formation. Both external and internal plexiform layers are thin. The latter, however is seen only in a few species. The internal granular layer, reaching the ventricular ependyma in some species, is a prominent component of the bulb. The pars dorsalis of the lateral olfactory tract usually courses between the mitral and internal granular layers. The chiropteran AOB does not differ in significant detail from that of insectivores, primates and other mammals. The occurrence of a functional vomeronasal system in the frugivorous, nectarivorous, and sanguivorous Phyllosotomatidae points to a primary functional role of this system in feeding strategy, at least in bats. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 PMID:7400042

  6. Beyond the olfactory bulb: An odotopic map in the forebrain

    PubMed Central

    Nikonov, Alexander A.; Finger, Thomas E.; Caprio, John

    2005-01-01

    We report electrophysiological evidence that a simple odotopy, the spatial mapping of different odorants, is maintained above the level of the olfactory bulb (OB). Three classes of biologically relevant odorants for fish are processed in distinct regions of the forebrain (FB) in the channel catfish. Feeding cues, mainly amino acids and nucleotides, are represented in lateral, pallial portions of the FB, equivalent to the olfactory cortex of amniote vertebrates, whereas social signals mediated by bile salts are represented in medial FB centers, possibly homologous to portions of the amygdala. As in the OB, the different odorant classes map onto different territories; however, the response properties of units of the olfactory areas of the FB do not simply mirror those of the OB. For some units, distinctive response properties emerged, because the FB is the first center where odors subserving a common behavioral function (i.e., food function) converge. PMID:16339016

  7. Chemotopic Representations of Aromatic Odorants in the Rat Olfactory Bulb

    PubMed Central

    Farahbod, Haleh; Johnson, Brett A.; Minami, S. Sakura; Leon, Michael

    2008-01-01

    Our laboratory has characterized spatial patterns of evoked neural activity across the entire glomerular layer of the rat olfactory bulb using primarily aliphatic odorants that differ systematically in functional groups and hydrocarbon structures. To represent more fully the true range of odorant chemistry, we have investigated aromatic compounds, which have a more rigid molecular structure than most aliphatic compounds and are particularly salient olfactory stimuli for humans. We first investigated glomerular patterns of 2-deoxyglucose uptake in response to aromatic compounds that differ in the nature and position of their functional groups (e.g., xylenes, trimethylbenzenes, tolualdehydes, benzaldehydes, methyl toluates, and anisaldehydes). We also studied the effects of systematic increases in the number and length of alkyl substituents. We found that most aromatic compounds activated glomeruli in the dorsal part of the bulb. Within this general area, aromatic odorants with oxygen-containing substituents favored activation of more rostral regions, and aromatic hydrocarbons activated more posterior regions. The nature of substituents greatly affected the pattern of glomerular activation, whereas isomers differing in substitution position evoked very similar overall patterns. These relationships between the structure of aromatic compounds and their spatial representation in the bulb are contrasted with our previous findings with aliphatic odorants. PMID:16736464

  8. Odor Enrichment Sculpts the Abundance of Olfactory Bulb Mitral Cells

    PubMed Central

    Johnson, Melissa Cavallin; Biju, K.C.; Hoffman, Joshua; Fadool, Debra Ann

    2013-01-01

    Mitral cells are the primary output cell from the olfactory bulb conveying olfactory sensory information to higher cortical areas. Gene-targeted deletion of the Shaker potassium channel Kv1.3 alters voltage-dependence and inactivation kinetics of mitral cell current properties, which contribute to the “Super-smeller” phenotype observed in Kv1.3-null mice. The goal of the current study was to determine if morphology and density are influenced by mitral cell excitability, olfactory environment, and stage of development. Wildtype (WT) and Kv1.3-null (KO) mice were exposed to a single odorant (peppermint or citralva) for 30 days. Under unstimulated conditions, postnatal day 20 KO mice had more mitral cells than their WT counterparts, but no difference in cell size. Odor-enrichment with peppermint, an olfactory and trigeminal stimulus, decreased the number of mitral cells in three month and one year old mice of both genotypes. Mitral cell density was most sensitive to odor-stimulation in three month WT mice. Enrichment at the same age with citralva, a purely olfactory stimulus, decreased cell density regardless of genotype. There were no significant changes in cell body shape in response to citralva exposure, but the cell area was greater in WT mice and selectively greater in the ventral region of the OB in KO mice. This suggests that trigeminal or olfactory stimulation may modify mitral cell area and density while not impacting cell body shape. Mitral cell density can therefore be modulated by the voltage and sensory environment to alter information processing or olfactory perception. PMID:23485739

  9. Odor Experience Facilitates Sparse Representations of New Odors in a Large-Scale Olfactory Bulb Model.

    PubMed

    Zhou, Shanglin; Migliore, Michele; Yu, Yuguo

    2016-01-01

    Prior odor experience has a profound effect on the coding of new odor inputs by animals. The olfactory bulb, the first relay of the olfactory pathway, can substantially shape the representations of odor inputs. How prior odor experience affects the representation of new odor inputs in olfactory bulb and its underlying network mechanism are still unclear. Here we carried out a series of simulations based on a large-scale realistic mitral-granule network model and found that prior odor experience not only accelerated formation of the network, but it also significantly strengthened sparse responses in the mitral cell network while decreasing sparse responses in the granule cell network. This modulation of sparse representations may be due to the increase of inhibitory synaptic weights. Correlations among mitral cells within the network and correlations between mitral network responses to different odors decreased gradually when the number of prior training odors was increased, resulting in a greater decorrelation of the bulb representations of input odors. Based on these findings, we conclude that the degree of prior odor experience facilitates degrees of sparse representations of new odors by the mitral cell network through experience-enhanced inhibition mechanism. PMID:26903819

  10. Odor Experience Facilitates Sparse Representations of New Odors in a Large-Scale Olfactory Bulb Model

    PubMed Central

    Zhou, Shanglin; Migliore, Michele; Yu, Yuguo

    2016-01-01

    Prior odor experience has a profound effect on the coding of new odor inputs by animals. The olfactory bulb, the first relay of the olfactory pathway, can substantially shape the representations of odor inputs. How prior odor experience affects the representation of new odor inputs in olfactory bulb and its underlying network mechanism are still unclear. Here we carried out a series of simulations based on a large-scale realistic mitral-granule network model and found that prior odor experience not only accelerated formation of the network, but it also significantly strengthened sparse responses in the mitral cell network while decreasing sparse responses in the granule cell network. This modulation of sparse representations may be due to the increase of inhibitory synaptic weights. Correlations among mitral cells within the network and correlations between mitral network responses to different odors decreased gradually when the number of prior training odors was increased, resulting in a greater decorrelation of the bulb representations of input odors. Based on these findings, we conclude that the degree of prior odor experience facilitates degrees of sparse representations of new odors by the mitral cell network through experience-enhanced inhibition mechanism. PMID:26903819

  11. Rat olfactory bulb mitral cells receive sparse glomerular inputs.

    PubMed

    Fantana, Antoniu L; Soucy, Edward R; Meister, Markus

    2008-09-11

    Center-surround receptive fields are a fundamental unit of brain organization. It has been proposed that olfactory bulb mitral cells exhibit this functional circuitry, with excitation from one glomerulus and inhibition from a broad field of glomeruli within reach of the lateral dendrites. We investigated this hypothesis using a combination of in vivo intrinsic imaging, single-unit recording, and a large panel of odors. Assuming a broad inhibitory field, a mitral cell would be influenced by >100 contiguous glomeruli and should respond to many odors. Instead, the observed response rate was an order of magnitude lower. A quantitative model indicates that mitral cell responses can be explained by just a handful of glomeruli. These glomeruli are spatially dispersed on the bulb and represent a broad range of odor sensitivities. We conclude that mitral cells do not have center-surround receptive fields. Instead, each mitral cell performs a specific computation combining a small and diverse set of glomerular inputs. PMID:18786363

  12. Serotonin increases synaptic activity in olfactory bulb glomeruli.

    PubMed

    Brill, Julia; Shao, Zuoyi; Puche, Adam C; Wachowiak, Matt; Shipley, Michael T

    2016-03-01

    Serotoninergic fibers densely innervate olfactory bulb glomeruli, the first sites of synaptic integration in the olfactory system. Acting through 5HT2A receptors, serotonin (5HT) directly excites external tufted cells (ETCs), key excitatory glomerular neurons, and depolarizes some mitral cells (MCs), the olfactory bulb's main output neurons. We further investigated 5HT action on MCs and determined its effects on the two major classes of glomerular interneurons: GABAergic/dopaminergic short axon cells (SACs) and GABAergic periglomerular cells (PGCs). In SACs, 5HT evoked a depolarizing current mediated by 5HT2C receptors but did not significantly impact spike rate. 5HT had no measurable direct effect in PGCs. Serotonin increased spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) in PGCs and SACs. Increased sEPSCs were mediated by 5HT2A receptors, suggesting that they are primarily due to enhanced excitatory drive from ETCs. Increased sIPSCs resulted from elevated excitatory drive onto GABAergic interneurons and augmented GABA release from SACs. Serotonin-mediated GABA release from SACs was action potential independent and significantly increased miniature IPSC frequency in glomerular neurons. When focally applied to a glomerulus, 5HT increased MC spontaneous firing greater than twofold but did not increase olfactory nerve-evoked responses. Taken together, 5HT modulates glomerular network activity in several ways: 1) it increases ETC-mediated feed-forward excitation onto MCs, SACs, and PGCs; 2) it increases inhibition of glomerular interneurons; 3) it directly triggers action potential-independent GABA release from SACs; and 4) these network actions increase spontaneous MC firing without enhancing responses to suprathreshold sensory input. This may enhance MC sensitivity while maintaining dynamic range. PMID:26655822

  13. Prenatal Stress Inhibits Hippocampal Neurogenesis but Spares Olfactory Bulb Neurogenesis

    PubMed Central

    Belnoue, Laure; Grosjean, Noelle; Ladevèze, Elodie

    2013-01-01

    The dentate gyrus (DG) and the olfactory bulb (OB) are two regions of the adult brain in which new neurons are integrated daily in the existing networks. It is clearly established that these newborn neurons are implicated in specific functions sustained by these regions and that different factors can influence neurogenesis in both structures. Among these, life events, particularly occurring during early life, were shown to profoundly affect adult hippocampal neurogenesis and its associated functions like spatial learning, but data regarding their impact on adult bulbar neurogenesis are lacking. We hypothesized that prenatal stress could interfere with the development of the olfactory system, which takes place during the prenatal period, leading to alterations in adult bulbar neurogenesis and in olfactory capacities. To test this hypothesis we exposed pregnant C57Bl/6J mice to gestational restraint stress and evaluated behavioral and anatomic consequences in adult male offspring. We report that prenatal stress has no impact on adult bulbar neurogenesis, and does not alter olfactory functions in adult male mice. However, it decreases cell proliferation and neurogenesis in the DG of the hippocampus, thus confirming previous reports on rats. Altogether our data support a selective and cross-species long-term impact of prenatal stress on neurogenesis. PMID:24009723

  14. Olfactory bulb monoamine concentrations vary with time of day.

    PubMed

    Corthell, J T; Stathopoulos, A M; Watson, C C; Bertram, R; Trombley, P Q

    2013-09-01

    The olfactory bulb (OB) has been recently identified as a circadian oscillator capable of operating independently of the master circadian pacemaker, the suprachiasmatic nuclei of the hypothalamus. OB oscillations manifest as rhythms in clock genes, electrical activity, and odor sensitivity. Dopamine, norepinephrine, and serotonin have been shown to modulate olfactory information processing by the OB and may be part of the mechanism that underlies diurnal changes in olfactory sensitivity. Rhythmic release of these neurotransmitters could generate OB rhythms in electrical activity and olfactory sensitivity. We hypothesized that these monoamines were rhythmically released in the OB. To test our hypotheses, we examined monoamine levels in the OB, over the course of a day, by high-performance liquid chromatography coupled to electrochemical detection. We observed that dopamine and its metabolite, 3-4-dihydroxyphenylacetic acid, rhythmically fluctuate over the day. In contrast, norepinephrine is arrhythmic. Serotonin and its metabolite hydroxyindoleacetic acid appear to rhythmically fluctuate. Each of these monoamines has been shown to alter OB circuit behavior and influence odor processing. Rhythmic release of serotonin may be a mechanism by which the suprachiasmatic nuclei communicate, indirectly, with the OB. PMID:23727009

  15. Odor Memory Stability after Reinnervation of the Olfactory Bulb

    PubMed Central

    Blanco-Hernández, Eduardo; Valle-Leija, Pablo; Zomosa-Signoret, Viviana; Drucker-Colín, René; Vidaltamayo, Román

    2012-01-01

    The olfactory system, particularly the olfactory epithelium, presents a unique opportunity to study the regenerative capabilities of the brain, because of its ability to recover after damage. In this study, we ablated olfactory sensory neurons with methimazole and followed the anatomical and functional recovery of circuits expressing genetic markers for I7 and M72 receptors (M72-IRES-tau-LacZ and I7-IRES-tau-GFP). Our results show that 45 days after methimazole-induced lesion, axonal projections to the bulb of M72 and I7 populations are largely reestablished. Furthermore, regenerated glomeruli are re-formed within the same areas as those of control, unexposed mice. This anatomical regeneration correlates with functional recovery of a previously learned odorant-discrimination task, dependent on the cognate ligands for M72 and I7. Following regeneration, mice also recover innate responsiveness to TMT and urine. Our findings show that regeneration of neuronal circuits in the olfactory system can be achieved with remarkable precision and underscore the importance of glomerular organization to evoke memory traces stored in the brain. PMID:23071557

  16. A TAP1 null mutation leads to an enlarged olfactory bulb and supernumerary, ectopic olfactory glomeruli

    PubMed Central

    Salcedo, Ernesto; Cruz, Nicole M.; Ly, Xuan; Welander, Beth A.; Hanson, Kyle; Kronberg, Eugene; Restrepo, Diego

    2013-01-01

    Major histocompatibility class I (MHCI) molecules are well known for their immunological role in mediating tissue graft rejection. Recently, these molecules were discovered to be expressed in distinct neuronal subclasses, dispelling the long-held tenet that the uninjured brain is immune-privileged. Here, we show that MHCI molecules are expressed in the main olfactory bulb (MOB) of adult animals. Furthermore, we find that mice with diminished levels of MHCI expression have enlarged MOBs containing an increased number of small, morphologically abnormal and ectopically located P2 glomeruli. These findings suggest that MHCI molecules may play an important role in the proper formation of glomeruli in the bulb. PMID:23697805

  17. Electrical recordings from the accessory olfactory bulb in VNO-AOB ex vivo preparations.

    PubMed

    Meeks, Julian P; Holy, Timothy E

    2013-01-01

    Electrical recordings from individual accessory olfactory bulb neurons allow exploration of the functional properties of this important pheromonal processing circuit. Several approaches to performing such recordings have been used. Here, we describe ex vivo methods that we have found useful for recording from accessory olfactory bulb neurons using simple extracellular glass electrodes. PMID:24014366

  18. 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

  19. 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

  20. Processing of odor mixtures in the zebrafish olfactory bulb.

    PubMed

    Tabor, Rico; Yaksi, Emre; Weislogel, Jan-Marek; Friedrich, Rainer W

    2004-07-21

    Components of odor mixtures often are not perceived individually, suggesting that neural representations of mixtures are not simple combinations of the representations of the components. We studied odor responses to binary mixtures of amino acids and food extracts at different processing stages in the olfactory bulb (OB) of zebrafish. Odor-evoked input to the OB was measured by imaging Ca2+ signals in afferents to olfactory glomeruli. Activity patterns evoked by mixtures were predictable within narrow limits from the component patterns, indicating that mixture interactions in the peripheral olfactory system are weak. OB output neurons, the mitral cells (MCs), were recorded extra- and intracellularly and responded to odors with stimulus-dependent temporal firing rate modulations. Responses to mixtures of amino acids often were dominated by one of the component responses. Responses to mixtures of food extracts, in contrast, were more distinct from both component responses. These results show that mixture interactions can result from processing in the OB. Moreover, our data indicate that mixture interactions in the OB become more pronounced with increasing overlap of input activity patterns evoked by the components. Emerging from these results are rules of mixture interactions that may explain behavioral data and provide a basis for understanding the processing of natural odor stimuli in the OB. PMID:15269273

  1. Olfactory bulb volume predicts therapeutic outcome in major depression disorder.

    PubMed

    Negoias, Simona; Hummel, Thomas; Symmank, Anja; Schellong, Julia; Joraschky, Peter; Croy, Ilona

    2016-06-01

    The volume of the olfactory bulb (OB) is strongly reduced in patients with major depressive disorder (MDD) and this group exhibits markedly decreased olfactory function. It has been suggested that olfactory input is important for maintaining balance in limbic neurocircuits. The aim of our study was to investigate whether reduced OB volume is associated with response to therapy in MDD. Twenty-four inpatients (all women, age 21-49 years, mean 38 ± 10 years SD) with MDD and 36 healthy controls (all women, age 20-52 years, mean 36 ± 10 years SD) underwent structural MRI. OB volume was compared between responders (N = 13) and non-responders (N = 11) to psychotherapy. Retest of OB volume was performed about 6 months after the end of therapy in nine of the patients. Therapy responders exhibited no significant difference in OB volume compared to healthy controls. However, average OB volume of non-responders was 23 % smaller compared to responders (p = .0011). Furthermore, OB volume was correlated with the change of depression severity (r = .46, p = .024). Volume of the OB did not change in the course of therapy. OB volume may be a biological vulnerability factor for the occurrence and/or maintenance of depression, at least in women. PMID:25977168

  2. Biophysical constraints on lateral inhibition in the olfactory bulb.

    PubMed

    McIntyre, Alexa B R; Cleland, Thomas A

    2016-06-01

    The mitral cells (MCs) of the mammalian olfactory bulb (OB) constitute one of two populations of principal neurons (along with middle/deep tufted cells) that integrate afferent olfactory information with top-down inputs and intrinsic learning and deliver output to downstream olfactory areas. MC activity is regulated in part by inhibition from granule cells, which form reciprocal synapses with MCs along the extents of their lateral dendrites. However, with MC lateral dendrites reaching over 1.5 mm in length in rats, the roles of distal inhibitory synapses pose a quandary. Here, we systematically vary the properties of a MC model to assess the capacity of inhibitory synaptic inputs on lateral dendrites to influence afferent information flow through MCs. Simulations using passivized models with varying dendritic morphologies and synaptic properties demonstrated that, even with unrealistically favorable parameters, passive propagation fails to convey effective inhibitory signals to the soma from distal sources. Additional simulations using an active model exhibiting action potentials, subthreshold oscillations, and a dendritic morphology closely matched to experimental values further confirmed that distal synaptic inputs along the lateral dendrite could not exert physiologically relevant effects on MC spike timing at the soma. Larger synaptic conductances representative of multiple simultaneous inputs were not sufficient to compensate for the decline in signal with distance. Reciprocal synapses on distal MC lateral dendrites may instead serve to maintain a common fast oscillatory clock across the OB by delaying spike propagation within the lateral dendrites themselves. PMID:27009162

  3. Retronasal odor representations in the dorsal olfactory bulb of rats

    PubMed Central

    Gautam, Shree Hari; Verhagen, Justus V.

    2012-01-01

    Animals perceive their olfactory environment not only from odors originating in the external world (orthonasal route) but also from odors released in the oral cavity while eating food (retronasal route). Retronasal olfaction is crucial for the perception of food flavor in humans. However, little is known about the retronasal stimulus coding in the brain. The most basic question is if and how route affects the odor representations at the level of the olfactory bulb (OB), where odor quality codes originate. We used optical calcium imaging of presynaptic dorsal OB responses to odorants in anesthetized rats to ask whether the rat OB could be activated retronasally, and how these responses compare to orthonasal responses under similar conditions. We further investigated the effects of specific odorant properties on orthoversus retronasal response patterns. We found that at a physiologically relevant flow rate retronasal odorants can effectively reach the olfactory receptor neurons, eliciting glomerular response patterns that grossly overlap with those of orthonasal responses, but differ from the orthonasal patterns in the response amplitude and temporal dynamics. Interestingly, such differences correlated well with specific odorant properties. Less volatile odorants yielded relatively smaller responses retronasally, but volatility did not affect relative temporal profiles. More polar odorants responded with relatively longer onset latency and time to peak retronasally, but polarity did not affect relative response magnitudes. These data provide insight into the early stages of retronasal stimulus coding and establish relationships between ortho- and retronasal odor representations in the rat OB. PMID:22674270

  4. RNA-seq analysis of developing olfactory bulb projection neurons.

    PubMed

    Kawasawa, Yuka Imamura; Salzberg, Anna C; Li, Mingfeng; Šestan, Nenad; Greer, Charles A; Imamura, Fumiaki

    2016-07-01

    Transmission of olfactory information to higher brain regions is mediated by olfactory bulb (OB) projection neurons, the mitral and tufted cells. Although mitral/tufted cells are often characterized as the OB counterpart of cortical projection neurons (also known as pyramidal neurons), they possess several unique morphological characteristics and project specifically to the olfactory cortices. Moreover, the molecular networks contributing to the generation of mitral/tufted cells during development are largely unknown. To understand the developmental patterns of gene expression in mitral/tufted cells in the OB, we performed transcriptome analyses targeting purified OB projection neurons at different developmental time points with next-generation RNA sequencing (RNA-seq). Through these analyses, we found 1202 protein-coding genes that are temporally differentially-regulated in developing projection neurons. Among them, 388 genes temporally changed their expression level only in projection neurons. The data provide useful resource to study the molecular mechanisms regulating development of mitral/tufted cells. We further compared the gene expression profiles of developing mitral/tufted cells with those of three cortical projection neuron subtypes, subcerebral projection neurons, corticothalamic projection neurons, and callosal projection neurons, and found that the molecular signature of developing olfactory projection neuron bears resemblance to that of subcerebral neurons. We also identified 3422 events that change the ratio of splicing isoforms in mitral/tufted cells during maturation. Interestingly, several genes expressed a novel isoform not previously reported. These results provide us with a broad perspective of the molecular networks underlying the development of OB projection neurons. PMID:27073125

  5. Histological and lectin histochemical studies on the main and accessory olfactory bulbs in the Japanese striped snake, Elaphe quadrivirgata.

    PubMed

    Kondoh, Daisuke; Wada, Akimi; Endo, Daisuke; Nakamuta, Nobuaki; Taniguchi, Kazuyuki

    2013-01-01

    The main and accessory olfactory bulbs were examined by histological methods and lectin histochemistry in the Japanese striped snake. As the results, the histological properties are similar between the main olfactory bulb and the accessory olfactory bulb. In lectin histochemistry, 21 lectins used in this study showed similar binding patterns in the main olfactory bulb and the accessory olfactory bulb. In detail, 15 lectins stained these olfactory bulbs with similar manner, and 6 lectins did not stain them at all. Two lectins, Lycopersicon esculentum lectin (LEL) and Solanum tuberosum lectin (STL), stained the nerve and glomerular layers and did not stain any other layers in both olfactory bulbs. Four lectins, Soybean agglutinin (SBA), Vicia villosa agglutinin (VVA), Peanut agglutinin (PNA) and Phaseolus vulgaris agglutinin-L (PHA-L) stained the nerve and glomerular layers more intensely than other layers in both olfactory bulbs. In addition, VVA showed the dot-like stainings in the glomeruli of both olfactory bulbs. These findings suggest that the degree of development and the properties of glycoconjugates are similar between the main olfactory bulb and the accessory olfactory bulb in the Japanese striped snake. PMID:23257605

  6. 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. PMID:25619656

  7. Neuropeptide Y-like immunoreactive neurons in the human olfactory bulb.

    PubMed

    Ohm, T G; Braak, E; Probst, A; Weindl, A

    1988-06-01

    Neuropeptide Y-like (NPY) immunoreactivity was localized in the adult human olfactory bulb by the unlabeled antibody enzyme (peroxidase anti-peroxidase; PAP) technique in vibratome sections. The majority of NPY-immunoreactive somata was localized in the white matter surrounding the anterior olfactory nucleus. Immunoreactive neurons were less numerous within the anterior olfactory nucleus and within the olfactory bulb layers. NPY-immunoreactive fibres were present in the white matter, the anterior olfactory nucleus, and in the olfactory bulb layers. Fibres within the white matter were generally aligned in a straight path parallel to the long axis of the olfactory bulb and tract. Fibres within the anterior olfactory nucleus showed no clear orientation and displayed numerous branching points. Coiled plexus of NPY-immunoreactive fibres were present in the glomerular layer of the olfactory bulb. Additional characteristics of the NPY-immunoreactive neurons were studied after decolouring the chromogen and restaining the sections with aldehydefuchsin to demonstrate the presence of lipofuscin granules and also with gallocyanin chrome alum to stain the Nissl substance. This analysis showed that the neurons belong to the class of non-pigmented nerve cells. PMID:3251589

  8. 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

  9. 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. PMID:16165240

  10. Ultrastructural analysis of olfactory ensheathing cells derived from olfactory bulb and nerve of neonatal and juvenile rats.

    PubMed

    Gómez, Rosa M; Ghotme, Kemel; Botero, Lucía; Bernal, Jaime E; Pérez, Rosalía; Barreto, George E; Bustos, Rosa Helena

    2016-02-01

    Olfactory nerve derived and olfactory bulb derived olfactory ensheathing cells (OECs) have the ability to promote axonal regeneration and remyelination, both of which are essential in a successful cell transplant. Thus, morphological identification of OECs is a key aspect to develop an applicable cell therapy for injuries to the nervous system. However, there is no clear definition regarding which developmental stage or anatomical origin of OECs is more adequate for neural repair. In the present study, an ultrastructural comparison was made between OECs recovered from primary cultures of olfactory nerve and bulb in two developmental stages. The most notorious difference between cells obtained from olfactory nerve and bulb was the presence of indented nuclei in bulb derived OECs, suggesting a greater ability for possible chemotaxis. In neonatal OECs abundant mitochondria, lipid vacuoles, and smooth endoplasmic reticulum were detected, suggesting an active lipid metabolism, probably involved in synthesis of myelin. Our results suggest that neonatal OECs obtained from olfactory bulb have microscopic properties that could make them more suitable for neural repair. PMID:26254553

  11. 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

  12. 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. PMID:26844880

  13. Osterix is dispensable for the development of the mouse olfactory bulb.

    PubMed

    Park, Ji-Soo; Park, Geon-Il; Kim, Jung-Eun

    2016-09-01

    Osterix (Osx) has been shown to be an osteoblast-specific transcription factor for bone formation. Recently, it has been reported that Osx is significantly expressed in the mouse olfactory bulb, proving that Osx may play a role in olfactory bulb development, as well as bone development. Here, we studied morphological differences and neuronal cell alterations in the olfactory bulb using an Osx gene-modified mouse model. Although Osx expression was reduced, morphological differences were not observed in the olfactory bulb of Osx heterozygous mice compared with that of wild-type mice. Immunofluorescence using the neuronal marker genes DCX, MAP2, NeuN, and GFAP showed neuronal cell alterations caused by Osx deficiency in the mitral cell layer (MCL) and granule cell layer (GCL) of the olfactory bulb at postnatal stage. The number, morphology, and expression patterns of immature neurons, mature neurons, and astrocytes were identical in both wild-type and Osx heterozygous mice. At the post-embryonic stage, the expression of neuronal markers DCX, Nestin, MAP2, and NeuN were examined in the MCL and GCL of the olfactory bulb in wild-type, Osx heterozygous, and Osx knockout embryos. Both DCX- and Nestin-positive immature neurons, and MAP2- and NeuN-positive mature neurons, revealed a similar expression pattern in all mouse types. These results indicated that olfactory bulb development was not significantly impaired in the absence of Osx. Further study may be necessary to explain the functional properties of the olfactory bulb caused by Osx deficiency. PMID:27449610

  14. Nisoxetine infusion into the olfactory bulb enhances the capacity for male rats to identify conspecifics.

    PubMed

    Shang, Y; Dluzen, D E

    2001-01-01

    In the present report, the norepinephrine uptake inhibitor nisoxetine as well as a cocktail of nisoxetine and the alpha-adrenergic receptor antagonist phentolamine were infused unilaterally into the olfactory bulb during microdialysis to assess their effects upon the capacity of male rats to identify conspecifics. A social discrimination test was conducted while simultaneously measuring olfactory bulb norepinephrine output in the dialysate before, during, and after behavioral testing. Nisoxetine significantly increased norepinephrine levels in the olfactory bulb compared with the Ringer's solution control group. Following such increases in olfactory bulb norepinephrine, identification responses were enhanced compared with that observed in the Ringer's control. In the presence of phentolamine, nisoxetine elevated olfactory bulb norepinephrine to levels similar to that obtained in the nisoxetine alone group, however, investigatory responses directed to the conspecifics indicated an absence of identification capacity similar to that observed in the Ringer's control group. These results reveal a direct link between norepinephrine transmission in the olfactory bulb and enhanced identification via its activation of postsynaptic alpha-adrenergic receptors. These results also show that inhibition of norepinephrine uptake may represent an important mechanism involved with the enhancement of social identification and suggest a possible novel effect for the antidepressant nisoxetine. PMID:11457583

  15. Dlx-Dependent and -Independent Regulation of Olfactory Bulb Interneuron Differentiation

    PubMed Central

    Long, Jason E.; Garel, Sonia; Alvarez-Dolado, Manuel; Yoshikawa, Kazuaki; Osumi, Noriko; Alvarez-Buylla, Arturo; Rubenstein, John L. R.

    2016-01-01

    Olfactory bulb interneuron development is a complex multistep process that involves cell specification in the ventral telencephalon, tangential migration into the olfactory bulb, and local neuronal maturation. Although several transcription factors have been implicated in this process, how or when they act remains to be elucidated. Here we explore the mechanisms that result in olfactory bulb interneuron defects in Dlx1&2−/− (distal-less homeobox 1 and 2) and Mash1−/− (mammalian achaete-schute homolog 1) mutants. We provide evidence that Dlx1&2 and Mash1 regulate parallel molecular pathways that are required for the generation of these cells, thereby providing new insights into the mechanisms underlying olfactory bulb development. The analysis also defined distinct anatomical zones related to olfactory bulb development. Finally we show that Dlx1&2 are required for promoting tangential migration to the olfactory bulb, potentially via regulating the expression of ErbB4 (v-erb-a erythroblastic leukemia viral oncogene homolog 4), Robo2 (roundabout homolog 2), Slit1 (slit homolog 1), and PK2 (prokineticin 2), which have all been shown to play essential roles in this migration. PMID:17376983

  16. Discharge patterning in rat olfactory bulb mitral cells in vivo

    PubMed Central

    Leng, Gareth; Hashimoto, Hirofumi; Tsuji, Chiharu; Sabatier, Nancy; Ludwig, Mike

    2014-01-01

    Abstract Here we present a detailed statistical analysis of the discharge characteristics of mitral cells of the main olfactory bulb of urethane‐anesthetized rats. Neurons were recorded from the mitral cell layer, and antidromically identified by stimuli applied to the lateral olfactory tract. All mitral cells displayed repeated, prolonged bursts of action potentials typically lasting >100 sec and separated by similarly long intervals; about half were completely silent between bursts. No such bursting was observed in nonmitral cells recorded in close proximity to mitral cells. Bursts were asynchronous among even adjacent mitral cells. The intraburst activity of most mitral cells showed strong entrainment to the spontaneous respiratory rhythm; similar entrainment was seen in some, but not all nonmitral cells. All mitral cells displayed a peak of excitability at ~25 msec after spikes, as reflected by a peak in the interspike interval distribution and in the corresponding hazard function. About half also showed a peak at about 6 msec, reflecting the common occurrence of doublet spikes. Nonmitral cells showed no such doublet spikes. Bursts typically increased in intensity over the first 20–30 sec of a burst, during which time doublets were rare or absent. After 20–30 sec (in cells that exhibited doublets), doublets occurred frequently for as long as the burst persisted, in trains of up to 10 doublets. The last doublet was followed by an extended relative refractory period the duration of which was independent of train length. In cells that were excited by application of a particular odor, responsiveness was apparently greater during silent periods between bursts than during bursts. Conversely in cells that were inhibited by a particular odor, responsiveness was only apparent when cells were active. Extensive raw (event timing) data from the cells, together with details of those analyses, are provided as supplementary material, freely available for secondary use

  17. Discharge patterning in rat olfactory bulb mitral cells in vivo.

    PubMed

    Leng, Gareth; Hashimoto, Hirofumi; Tsuji, Chiharu; Sabatier, Nancy; Ludwig, Mike

    2014-10-01

    Here we present a detailed statistical analysis of the discharge characteristics of mitral cells of the main olfactory bulb of urethane-anesthetized rats. Neurons were recorded from the mitral cell layer, and antidromically identified by stimuli applied to the lateral olfactory tract. All mitral cells displayed repeated, prolonged bursts of action potentials typically lasting >100 sec and separated by similarly long intervals; about half were completely silent between bursts. No such bursting was observed in nonmitral cells recorded in close proximity to mitral cells. Bursts were asynchronous among even adjacent mitral cells. The intraburst activity of most mitral cells showed strong entrainment to the spontaneous respiratory rhythm; similar entrainment was seen in some, but not all nonmitral cells. All mitral cells displayed a peak of excitability at ~25 msec after spikes, as reflected by a peak in the interspike interval distribution and in the corresponding hazard function. About half also showed a peak at about 6 msec, reflecting the common occurrence of doublet spikes. Nonmitral cells showed no such doublet spikes. Bursts typically increased in intensity over the first 20-30 sec of a burst, during which time doublets were rare or absent. After 20-30 sec (in cells that exhibited doublets), doublets occurred frequently for as long as the burst persisted, in trains of up to 10 doublets. The last doublet was followed by an extended relative refractory period the duration of which was independent of train length. In cells that were excited by application of a particular odor, responsiveness was apparently greater during silent periods between bursts than during bursts. Conversely in cells that were inhibited by a particular odor, responsiveness was only apparent when cells were active. Extensive raw (event timing) data from the cells, together with details of those analyses, are provided as supplementary material, freely available for secondary use by others. PMID

  18. A Circadian Clock in the Olfactory Bulb Anticipates Feeding during Food Anticipatory Activity

    PubMed Central

    Nolasco, Nahum; Juárez, Claudia; Morgado, Elvira; Meza, Enrique; Caba, Mario

    2012-01-01

    Rabbit pups ingest food, in this case milk, once a day with circadian periodicity and are a natural model of food anticipatory activity. During nursing, several sensory systems receive information about properties of the food, one of them being the olfactory system, which has received little attention in relation to synchronization by food. In addition, the olfactory bulb has a circadian pacemaker that exhibits rhythms independently of the suprachiasmatic nucleus, but the biological functions of these rhythms are largely unknown. In the present contribution, we hypothesized that circadian suckling of milk synchronizes rhythms in the olfactory bulb. To this aim we explored by immunohistochemistry, rhythms of FOS and PER1 proteins, as indicators of activation and reporter of oscillations, respectively, through a complete 24-h cycle in periglomerular, mitral and granular cell layers of both the main and the accessory olfactory bulb. Subjects were 7-day-old rabbit pups scheduled to nurse during the night (02∶00 h) or day (10∶00 h), and also fasted subjects, to explore the possible persistence of oscillations. In the three layers of the main olfactory bulb, FOS was high at time of nursing, then further increased 1.5 h afterward, and then decreased to increase again in advance of the next nursing bout. This pattern persisted, without the postprandial increase, in fasted subjects with a shift in subjects nursed at 02∶00. PER1 was increased 2–8 h after nursing and this increase persisted in most cell layers, with a shift, in fasted subjects. In the accessory olfactory bulb we only observed a consistent pattern of FOS expression in the mitral cell layer of nursed subjects, similar to that of the main olfactory bulb. We conclude that the main olfactory bulb is synchronized during milk ingestion, but during fasting its oscillations perhaps are modulated by the suprachiasmatic nucleus, as proposed for rodents. PMID:23094084

  19. 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

  20. 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

  1. 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

  2. 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

  3. Secretagogin-containing neurons in the mouse main olfactory bulb.

    PubMed

    Kosaka, Katsuko; Kosaka, Toshio

    2013-01-01

    Secretagogin (SCGN) is a recently discovered calcium binding protein of the EF hand family. We studied the structural features of SCGN-positive neurons in the mouse main olfactory bulb (MOB). SCGN-positive neurons were localized throughout layers but clustered in the glomerular layer (GL), mitral cell layer (MCL) and granule cell layer (GCL). They were heterogeneous, including numerous juxtaglomerular neurons, granule cells, small to medium-sized neurons in the external plexiform layer (EPL), and a few small cells in the ependymal/subependymal layer. Calretinin and/or tyrosine hydroxylase occasionally colocalized in SCGN-positive juxtaglomerular neurons. Calretinin also frequently colocalized in SCGN-positive EPL and GCL neurons. Morphologically some of juxtaglomerular SCGN-positive neurons were classical periglomerular cells, whereas others were apparently different from those periglomerular cells, although they were further heterogeneous. Some extended one slender process into a glomerulus which passed the glomerulus and further penetrated into another nearby glomeruli, and thus their dendritic processes spanned two or three or more glomeruli. We named this type of juxtaglomerular neurons "transglomerular cells." With the stereological analysis we estimated total number of juxtaglomerular SCGN-positive neurons at about 80,000/single MOB. The present study revealed the diversity of SCGN-positive neurons in the mouse MOB and their particular structural properties hitherto unknown. PMID:24008127

  4. Existence of Gαi2-expressing axon terminals in the goat main olfactory bulb.

    PubMed

    Ohara, Hiromi; Okamura, Hiroaki; Ichikawa, Masumi; Mori, Yuji; Hagino-Yamagishi, Kimiko

    2013-01-31

    In rodents, Gα(i2)-expressing sensory neurons (SNs) that co-express vomeronasal receptor type 1 (V1R) are specifically found in the vomeronasal organ (VNO) and project their axons to the accessory olfactory bulb (AOB). In goats, however, Gα(i2)/V1R-expressing SNs exist in both the VNO and the olfactory epithelium. Thus, we examined whether the Gα(i2)-expressing axons functionally project to the main olfactory bulb (MOB). We analyzed the expression of Gα(i2) in the olfactory bulb and found small Gα(i2)-immunoreactive clusters in the MOB. The Gα(i2)-immunoreactive axons in these clusters made synaptic contacts with second-order neurons in the MOB. These results suggest that some Gα(i2)-expressing SNs functionally project their axons to the MOB in goats. PMID:22878538

  5. Microdialysis pharmacokinetic study of scopolamine in plasma, olfactory bulb and vestibule after intranasal administration.

    PubMed

    Wei, Yan; Ying, Mingzhen; Xu, Shuai; Wang, Feng; Zou, Aifeng; Cao, Shilei; Jiang, Xinguo; Wang, Yajie

    2016-01-01

    The purpose of this study was to investigate the microdialysis pharmacokinetic of scopolamine in plasma, olfactory bulb and vestibule after intranasal administration. The pharmacokinetic study of subcutaneous and oral administration was also performed in rats. From the in vivo results, scopolamine intranasal administration can avoid hepatic first-pass effect. Tmax plasma samples after intranasal administration were significantly faster than oral administration and subcutaneous injection. The relative bioavailability of intranasal administrations was 51.8-70% when compared with subcutaneous injection. Moreover, one can see that in comparison with scopolamine subcutaneous administration, scopolamine intranasal gel and solutions can increased drug target index (DTI) with olfactory bulb 1.69 and 2.05, vestibule 1.80 and 2.15, respectively. The results indicated that scopolamine can be absorbed directly through the olfactory mucosa into the olfactory bulb, and then transported to various brain tissue after intranasal administration, with the characteristics of brain drug delivery. PMID:24865285

  6. 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. PMID:10880997

  7. Age-related changes in p2 odorant receptor mapping in the olfactory bulb.

    PubMed

    Costanzo, Richard M; Kobayashi, Masayoshi

    2010-06-01

    The ability to identify odors is dependent on the spatial mapping of odorant receptors onto fixed positions within the olfactory bulb. In elderly adults, odor identification and discrimination is often impaired. The objective of this study was to determine if there are age-related changes in odorant receptor mapping. We studied 8 groups of mice ranging in age from 2 weeks to 2.5 years and mapped the projection of P2 odorant receptors onto targeted glomeruli within medial and lateral domains of the olfactory bulb. A total of 60 mice were used to measure the number of P2 glomeruli, bulb length, the position of each glomerulus, and the amount of P2 axons targeting each glomerulus. We found that over 70% of olfactory bulbs contained multiple P2 glomeruli, bulb length increased 42% between the ages of 2 and 13 weeks, and the position of P2 glomeruli shifted with bulb growth. In most cases, targeted glomeruli were either completely or partially filled with P2 axons. In some cases, targeting was diffuse, with glomeruli receiving only a few stray P2-labeled axons. The frequency of diffuse targeting was rare (<4%) in adult mice 3-6 months in age. However, significant increases in diffuse targeting were observed in older mice, reaching 10% at 1 year and 22% at 2 years of age. These findings suggest that odorant receptor mapping becomes more disrupted in old age and could account for impaired olfactory function in elderly adults. PMID:20231263

  8. Dendrodendritic synapses in the mouse olfactory bulb external plexiform layer.

    PubMed

    Bartel, Dianna L; Rela, Lorena; Hsieh, Lawrence; Greer, Charles A

    2015-06-01

    Odor information relayed by olfactory bulb projection neurons, mitral and tufted cells (M/T), is modulated by pairs of reciprocal dendrodendritic synaptic circuits in the external plexiform layer (EPL). Interneurons, which are accounted for largely by granule cells, receive depolarizing input from M/T dendrites and in turn inhibit current spread in M/T dendrites via hyperpolarizing reciprocal dendrodendritic synapses. Because the location of dendrodendritic synapses may significantly affect the cascade of odor information, we assessed synaptic properties and density within sublaminae of the EPL and along the length of M/T secondary dendrites. In electron micrographs the M/T to granule cell synapse appeared to predominate and was equivalent in both the outer and inner EPL. However, the dendrodendritic synapses from granule cell spines onto M/T dendrites were more prevalent in the outer EPL. In contrast, individual gephyrin-immunoreactive (IR) puncta, a postsynaptic scaffolding protein at inhibitory synapses used here as a proxy for the granule to M/T dendritic synapse was equally distributed throughout the EPL. Of significance to the organization of intrabulbar circuits, gephyrin-IR synapses are not uniformly distributed along M/T secondary dendrites. Synaptic density, expressed as a function of surface area, increases distal to the cell body. Furthermore, the distributions of gephyrin-IR puncta are heterogeneous and appear as clusters along the length of the M/T dendrites. Consistent with computational models, our data suggest that temporal coding in M/T cells is achieved by precisely located inhibitory input and that distance from the soma is compensated for by an increase in synaptic density. PMID:25420934

  9. Dendrodendritic Synapses in the Mouse Olfactory Bulb External Plexiform Layer

    PubMed Central

    Bartel, Dianna L.; Rela, Lorena; Hsieh, Lawrence; Greer, Charles A.

    2014-01-01

    Odor information relayed by olfactory bulb projection neurons, mitral and tufted cells (M/T), is modulated by pairs of reciprocal dendrodendritic synaptic circuits in the external plexiform layer (EPL). Interneurons, which are accounted for largely by granule cells, receive depolarizing input from M/T dendrites and in turn inhibit current spread in M/T dendrites via hyperpolarizing reciprocal dendrodendritic synapses. Because the location of dendrodendritic synapses may significantly affect the cascade of odor information, we assessed synaptic properties and density within sublaminae of the EPL and along the length of M/T secondary dendrites. In electron micrographs the M/T to granule cell synapse appeared to predominate and were equivalent in both the outer and inner EPL. However, the dendrodendritic synapses from granule cell spines onto M/T dendrites, were more prevalent in the outer EPL. In contrast, individual gephyrin-IR puncta, a postsynaptic scaffolding protein at inhibitory synapses used here as a proxy for the granule to M/T dendritic synapse was equally distributed throughout the EPL. Of significance to the organization of intrabulbar circuits, gephyrin-IR synapses are not uniformly distributed along M/T secondary dendrites. Synaptic density, expressed as a function of surface area, increases distal to the cell body. Furthermore, the distributions of gephyrin-IR puncta are heterogeneous and appear as clusters along the length of the M/T dendrites. Consistent with computational models, our data suggest that temporal coding in M/T cells is achieved by precisely located inhibitory input and that distance from the soma is compensated with an increase in synaptic density. PMID:25420934

  10. Olfactory aversive conditioning alters olfactory bulb mitral/tufted cell glomerular odor responses

    PubMed Central

    Fletcher, Max L.

    2012-01-01

    The anatomical organization of receptor neuron input into the olfactory bulb (OB) allows odor information to be transformed into an odorant-specific spatial map of mitral/tufted (M/T) cell glomerular activity at the upper level of the OB. In other sensory systems, neuronal representations of stimuli can be reorganized or enhanced following learning. While the mammalian OB has been shown to undergo experience-dependent plasticity at the glomerular level, it is still unclear if similar representational change occurs within (M/T) cell glomerular odor representations following learning. To address this, odorant-evoked glomerular activity patterns were imaged in mice expressing a GFP-based calcium indicator (GCaMP2) in OB (M/T) cells. Glomerular odor responses were imaged before and after olfactory associative conditioning to aversive foot shock. Following conditioning, we found no overall reorganization of the glomerular representation. Training, however, did significantly alter the amplitudes of individual glomeruli within the representation in mice in which the odor was presented together with foot shock. Further, the specific pairing of foot shock with odor presentations lead to increased responses primarily in initially weakly activated glomeruli. Overall, these results suggest that associative conditioning can enhance the initial representation of odors within the OB by enhancing responses to the learned odor in some glomeruli. PMID:22461771

  11. Somatostatin-14-like immunoreactive neurons and fibres in the human olfactory bulb.

    PubMed

    Ohm, T G; Braak, E; Probst, A

    1988-01-01

    This study describes the morphological features and the distribution pattern of neurons in the human olfactory bulb which are immunoreactive for an antiserum against the neuropeptide somatostatin-14. Immunoreactive nerve cell bodies were mainly found in the white matter surrounding the cell clusters of the anterior olfactory nucleus. Some immunoreactive neurons were also found scattered throughout the anterior olfactory nucleus and the deeper parts of the inner granule cell layer. Only a few immunoreactive neurons were localized in the glomerular layer and the outer granule cell layer. Immunoreactive fibres were found in all layers of the olfactory bulb. In addition, an impressive number of coiled and kinked immunoreactive fibres were localized within the anterior olfactory nucleus forming a dense plexus. Accumulations of twisted and coiled branches of immunoreactive fibres were rarely found either surrounding or within the olfactory glomerula. The characteristics of somatostatin-14 immunoreactive neurons as seen in the combined pigment-Nissl preparation were studied after decolourizing the chromogen and restaining the preparations with aldehydefuchsin in order to demonstrate the lipofuscin pigment and gallocyanin chrome alum for Nissl material. About 90% of the immunoreactive neurons studied in this manner turned out to be devoid of lipofuscin granules. The remaining 10% displayed different patterns of pigmentation. These findings suggest the presence of different types of somatostatin-14-like immunoreactive neurons in the olfactory bulb of the human adult. PMID:2906788

  12. Dense EM-based reconstruction of the interglomerular projectome in the zebrafish olfactory bulb.

    PubMed

    Wanner, Adrian A; Genoud, Christel; Masudi, Tafheem; Siksou, Léa; Friedrich, Rainer W

    2016-06-01

    The dense reconstruction of neuronal circuits from volumetric electron microscopy (EM) data has the potential to uncover fundamental structure-function relationships in the brain. To address bottlenecks in the workflow of this emerging methodology, we developed a procedure for conductive sample embedding and a pipeline for neuron reconstruction. We reconstructed ∼98% of all neurons (>1,000) in the olfactory bulb of a zebrafish larva with high accuracy and annotated all synapses on subsets of neurons representing different types. The organization of the larval olfactory bulb showed marked differences from that of the adult but similarities to that of the insect antennal lobe. Interneurons comprised multiple types but granule cells were rare. Interglomerular projections of interneurons were complex and bidirectional. Projections were not random but biased toward glomerular groups receiving input from common types of sensory neurons. Hence, the interneuron network in the olfactory bulb exhibits a specific topological organization that is governed by glomerular identity. PMID:27089019

  13. 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. PMID:26161908

  14. A population of glomerular glutamatergic neurons controls sensory information transfer in the mouse olfactory bulb

    PubMed Central

    Tatti, Roberta; Seal, Rebecca P.; Edwards, Robert H.; Rodriguez, Ivan; Carleton, Alan

    2014-01-01

    In sensory systems, peripheral organs convey sensory inputs to relay networks where information is shaped by local microcircuits before being transmitted to cortical areas. In the olfactory system, odorants evoke specific patterns of sensory neuron activity which are transmitted to output neurons in olfactory bulb glomeruli. How sensory information is transferred and shaped at this level remains still unclear. Here we employ mouse genetics, 2-photon microscopy, electrophysiology and optogenetics, to identify a novel population of glutamatergic neurons (VGLUT3+) in the glomerular layer of the adult mouse olfactory bulb as well as several of their synaptic targets. Both peripheral and serotoninergic inputs control VGLUT3+ neurons firing. Furthermore, we show that VGLUT3+ neurons photostimulation in vivo strongly suppresses both spontaneous and odor-evoked firing of bulbar output neurons. In conclusion, we identify and characterize here a microcircuit controlling the transfer of sensory information at an early stage of the olfactory pathway. PMID:24804702

  15. Activity-Induced Remodeling of Olfactory Bulb Microcircuits Revealed by Monosynaptic Tracing

    PubMed Central

    Arenkiel, Benjamin R.; Hasegawa, Hiroshi; Yi, Jason J.; Larsen, Rylan S.; Wallace, Michael L.; Philpot, Benjamin D.; Wang, Fan; Ehlers, Michael D.

    2011-01-01

    The continued addition of new neurons to mature olfactory circuits represents a remarkable mode of cellular and structural brain plasticity. However, the anatomical configuration of newly established circuits, the types and numbers of neurons that form new synaptic connections, and the effect of sensory experience on synaptic connectivity in the olfactory bulb remain poorly understood. Using in vivo electroporation and monosynaptic tracing, we show that postnatal-born granule cells form synaptic connections with centrifugal inputs and mitral/tufted cells in the mouse olfactory bulb. In addition, newly born granule cells receive extensive input from local inhibitory short axon cells, a poorly understood cell population. The connectivity of short axon cells shows clustered organization, and their synaptic input onto newborn granule cells dramatically and selectively expands with odor stimulation. Our findings suggest that sensory experience promotes the synaptic integration of new neurons into cell type-specific olfactory circuits. PMID:22216277

  16. 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

  17. 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…

  18. The Olfactory Bulb: An Immunosensory Effector Organ during Neurotropic Viral Infections.

    PubMed

    Durrant, Douglas M; Ghosh, Soumitra; Klein, Robyn S

    2016-04-20

    In 1935, the olfactory route was hypothesized to be a portal for virus entry into the central nervous system (CNS). This hypothesis was based on experiments in which nasophayngeal infection with poliovirus in monkeys was prevented from spreading to their CNS via transection of olfactory tracts between the olfactory neuroepithelium (ONE) of the nasal cavity and the olfactory bulb (OB). Since then, numerous neurotropic viruses have been observed to enter the CNS via retrograde transport along axons of olfactory sensory neurons whose cell bodies reside in the ONE. Importantly, this route of infection can occur even after subcutaneous inoculation of arboviruses that can cause encephalitis in humans. While the olfactory route is now accepted as an important pathway for viral entry into the CNS, it is unclear whether it provides a way for infection to spread to other brain regions. More recently, studies of antiviral innate and adaptive immune responses within the olfactory bulb suggest it provides early virologic control. Here we will review the data demonstrating that neurotropic viruses gain access to the CNS initially via the olfactory route with emphasis on findings that suggest the OB is a critical immunosensory effector organ that effectively clears virus. PMID:27058872

  19. Olfactory bulb ablation in the rat: behavioural changes and their reversal by antidepressant drugs.

    PubMed Central

    van Riezen, H; Schnieden, H; Wren, A F

    1977-01-01

    1. The effects of bilateral olfactory bulbectomy, sham-operation and inducement of peripheral anosmia were studied on locomotor activity, passive avoidance acquisition and irritability. 2. Bulbectomized rats were hyperactive, deficient at learning a step-down passive avoidance response and hyperirritable. Peripheral anosmia, induced by intranasal infusion of ZnSO4 solution resulted in no behavioural changes. 3. Chronic pretreatment with amitriptyline (3 and 10 mg/kg) and a tetracyclic antidepressant mianserin (Org GB 94, 5 and 15 mg/kg) reversed the hyperactivity and reduced the learning deficit of bulbectomized rats. These drugs had no significant effects on sham-operated animals. 4. Neither amitriptyline nor mianserin reduced the exaggerated responses of bulbectomized rats to external stimuli. 5. (+)-Amphetamine (1 and 3 mg/kg) accelerated the acquisition of the passive avoidance response, greatly enhanced the locomotor activity and slightly increased the irritability score of both sham-operated and bulbectomized rats. 6. Chlorpromazine (1 and 3 mg/kg) and chlordiazepoxide (10 mg/kg) significantly reduced the acquisition, locomotor activity and irritability of experimental and control rats. 7. Lithium sulphate (1 and 3 mg/kg) had no effect on activity or irritability but produced a small impairment in acquistion of bulbectomized rats. 8. It is concluded that the reversal by antidepressant drugs of the behavioural syndrome seen after olfactory bulb ablation could constitute a new model for the detection of this group of centrally acting compounds. PMID:907867

  20. 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.

  1. Investigating the roles of odor-evoked oscillations in information processing in the turtle olfactory bulb

    NASA Astrophysics Data System (ADS)

    Kim, Soyoun

    It has been earlier established that presentation of an odorant stimulus to the turtle evokes specific spatio-temporal responses in the olfactory bulb. This response includes three distinct oscillatory patterns (rostral, middle and caudal) that have different spatial (locations and scopes) and temporal (frequencies and delay from the odorant onset) properties. In this thesis we investigate, using modeling and experimental approaches; the mechanisms of formation and the role of the oscillatory patterning in the turtle olfactory bulb. We have built a computational model that incorporates the basic anatomy and neurophysiology of the olfactory bulb to investigate how the observed patterns relate to activity of individual neurons and what roles they could play in olfactory information processing. We show that three basic anatomical/physiological properties of the olfactory network underlie formation of a temporal sequence of simultaneous activations of glomerular modules: fast synaptic inhibition between populations of excitatory and inhibitory cells, slow self-inhibition observed on excitatory cells; and input strength. The model suggests that the role of oscillations is to organize the neural activity in a temporal sequence which groups the activation of glomerular modules based on the input strength similarity. We show that this type of code explains particularly well the experimental findings reported also by other groups, showing that temporal patterning may mediate discrimination of similar odorants. Furthermore, we showed that within our model, feedback from cortical regions of the brain could modulate oscillatory patterning and provide mechanisms to generate experimentally observed period doubling in one of the oscillations. This requires the cortical processing to act as a type of coincidence modulator and provide functional coupling between excitatory modules that is absent in the bulbar network. This hypothesis is partially supported by our experiments that

  2. In goldfish the discriminative ability for odours persists after reduction of the olfactory epithelium, and rapidly returns after olfactory nerve axotomy and crossing bulbs.

    PubMed

    Zippel, H P

    2000-09-29

    Goldfish are ideal vertebrates for the study of regeneration within the peripheral and the central olfactory system. The present behavioural investigations studied the effects of bilateral lesions on the animals' ability to qualitatively discriminate two amino acids (10(-6) M) and their performance in two more difficult tasks: (i) rewarded amino acid applied in a lower concentration, and (ii) rewarded stimulus contaminated. A 50 and 85% reduction of the olfactory epithelium resulted in no recordable behavioural deficit. After axotomy of olfactory nerves and lateral olfactory tractotomy, fishes were anosmic for seven to ten days. Following replacement of sensory cells in the epithelium, and after regeneration of olfactory tract fibres a full functional recovery i.e. a highly specific regeneration, was recorded. After three surgical modifications of the olfactory bulbs' position, (i) crossing olfactory tracts and bulbs, (ii) crossing tracts and turning bulbs, and (iii) turning bulbs upside down, a full functional recovery was recorded for amino-acid discrimination in a similar concentration. A permanent, and similar slight deficit was, however, found during application of different concentrations, and of contaminated stimuli when medial lateral halves of the bulb were in 'incorrect' position (i) and (ii), or olfactory bulbs were positioned in the vicinity of the contralateral epithelium (i) and (ii). PMID:11079402

  3. 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

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

    PubMed

    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

  5. α-Synuclein aggregation in the olfactory bulb of middle-aged common marmoset.

    PubMed

    Kobayashi, Reona; Takahashi-Fujigasaki, Junko; Shiozawa, Seiji; Hara-Miyauchi, Chikako; Inoue, Takashi; Okano, Hirotaka James; Sasaki, Erika; Okano, Hideyuki

    2016-05-01

    The synaptic protein α-synuclein has been identified as a major component of Lewy bodies, a pathological hallmark of Parkinson's disease (PD). Prior to the formation of Lewy bodies, mislocalization and aggregation of the α-synuclein in brain tissue is frequently observed in various neurodegenerative diseases. Aberrant accumulation and localization of α-synuclein are also observed in the aging human brain, for which reason aging is regarded as a risk factor for neurodegenerative disease. To investigate changes in α-synuclein properties in the aging brain, we compared α-synuclein immunoreactivity in brain tissue of young (2-years-old) and middle-aged (6-years-old) common marmoset (Callithrix jacchus). Our analyses revealed marked changes in α-synuclein immunoreactivity in the olfactory bulb of common marmosets of these age cohorts. Perikaryal α-synuclein aggregations were formed in the olfactory bulb in middle-aged animals. We also observed signals of α-synuclein accumulation in hippocampus in this cohort; however, unlike in the olfactory bulb, hippocampal α-synuclein signals were localized in the synaptic terminals. We did not observe either of these features in younger marmosets, which suggest that aging may play a role in these phenomena. Our results using common marmoset brain corresponded with the observation that the α-synuclein aggregations were first occurred from olfactory bulb in human normal aged and PD brain. Therefore, common marmoset is expected as useful model for α-synuclein pathology. PMID:26643383

  6. 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

  7. 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. PMID:26586152

  8. Implementation of Olfactory Bulb Glomerular-Layer Computations in a Digital Neurosynaptic Core

    PubMed Central

    Imam, Nabil; Cleland, Thomas A.; Manohar, Rajit; Merolla, Paul A.; Arthur, John V.; Akopyan, Filipp; Modha, Dharmendra S.

    2012-01-01

    We present a biomimetic system that captures essential functional properties of the glomerular layer of the mammalian olfactory bulb, specifically including its capacity to decorrelate similar odor representations without foreknowledge of the statistical distributions of analyte features. Our system is based on a digital neuromorphic chip consisting of 256 leaky-integrate-and-fire neurons, 1024 × 256 crossbar synapses, and address-event representation communication circuits. The neural circuits configured in the chip reflect established connections among mitral cells, periglomerular cells, external tufted cells, and superficial short-axon cells within the olfactory bulb, and accept input from convergent sets of sensors configured as olfactory sensory neurons. This configuration generates functional transformations comparable to those observed in the glomerular layer of the mammalian olfactory bulb. Our circuits, consuming only 45 pJ of active power per spike with a power supply of 0.85 V, can be used as the first stage of processing in low-power artificial chemical sensing devices inspired by natural olfactory systems. PMID:22685425

  9. A two-layer biophysical model of cholinergic neuromodulation in olfactory bulb

    PubMed Central

    Li, Guoshi; Cleland, Thomas A.

    2013-01-01

    Cholinergic inputs from the basal forebrain regulate multiple olfactory bulb (OB) functions including odor discrimination, perceptual learning, and short term memory. Previous studies have shown that nicotinic cholinergic receptor activation sharpens mitral cell chemoreceptive fields, likely via intraglomerular circuitry. Muscarinic cholinergic activation is less well understood, though muscarinic receptors are implicated in olfactory learning and in the regulation of synchronized oscillatory dynamics in hippocampus and cortex. To understand the mechanisms underlying cholinergic neuromodulation in OB, we developed a biophysical model of the OB neuronal network including both glomerular layer and external plexiform layer (EPL) computations and incorporating both nicotinic and muscarinic neuromodulatory effects. Our simulations show how nicotinic activation within glomerular circuits sharpens mitral cell chemoreceptive fields, even in the absence of EPL circuitry, but does not facilitate intrinsic oscillations or spike synchronization. In contrast, muscarinic receptor activation increases mitral cell spike synchronization and field oscillatory power by potentiating granule cell excitability and lateral inhibitory interactions within the EPL, but has little effect on mitral cell firing rates and hence will not sharpen olfactory representations under a rate metric. These results are consistent with the theory that EPL interactions regulate the timing, rather than the existence, of mitral cell action potentials, and perform their computations with respect to a spike timing-based metric. This general model suggests that the roles of nicotinic and muscarinic receptors in olfactory bulb are both distinct and complementary to one another, together regulating the effects of ascending cholinergic inputs on olfactory bulb transformations. PMID:23407960

  10. 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

  11. 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.

  12. Transneuronal regulation of neuronal specific gene expression in the mouse olfactory bulb.

    PubMed

    Ehrlich, M E; Grillo, M; Joh, T H; Margolis, F L; Baker, H

    1990-02-01

    Peripheral afferent denervation (deafferentation) of the rodent main olfactory bulb produces a marked decrease in tyrosine hydroxylase (TH) activity and immunoreactivity in a population of juxtaglomerular dopaminergic neurons. Preservation of activity and immunostaining for aromatic L-amino acid decarboxylase implies that these cells do not die, but change phenotype. We now report that the steady-state level of TH mRNA markedly decreases in the adult mouse olfactory bulb in response to deafferentation. This reduction is permanent following intranasal irrigation with 0.17 M zinc sulphate (ZnSO4) but reversible following deafferentation produced by intranasal irrigation with 0.7% Triton X-100. The initial declines in TH activity, protein and mRNA of dopaminergic juxtaglomerular neurons observed after Triton X-100 treatment are all reversible as the steady-state level of TH mRNA gradually returns to control levels. Steady-state levels of mRNA for olfactory marker protein (OMP), a protein found in high concentrations in olfactory receptor neurons and their processes which innervate the olfactory bulb, were also monitored following deafferentation. Following treatment with either ZnSO4 or Triton X-100, the pattern of changes in steady-state levels of OMP mRNA was similar to that observed for TH. The steady-state level of PEP19 mRNA, a peptide previously localized to granule cells in the olfactory bulb, was not altered by deafferentation. These data indicate selective and parallel regulation of TH and OMP message and protein levels following deafferentation. PMID:1971084

  13. Reduced olfactory bulb volume in adults with a history of childhood maltreatment.

    PubMed

    Croy, Ilona; Negoias, Simona; Symmank, Anja; Schellong, Julia; Joraschky, Peter; Hummel, Thomas

    2013-10-01

    The human olfactory bulb (OB) is the first relay station of the olfactory pathway and may have the potential for postnatal neurogenesis in early childhood. In animals, chronic stress affects the OB and olfactory functioning. For humans, it has been shown that major depressive disorder is accompanied by reduced OB volume and reduced olfactory function. However, it is not clear if major stress in childhood development also affects olfactory functioning and OB volume in humans. OB volume was measured and olfactory function was tested in 17 depressive patients with and 10 without a history of severe childhood maltreatment (CM). CM patients exhibited a significantly reduced olfactory threshold and identification ability. The OB volume of the CM patients was significantly reduced to 80% of the non-CM patients. In conclusion, postnatal neurogenesis might be by reduced in CM, which may affect olfactory function of the brain in later life. Alternatively, a reduced OB volume may enhance psychological vulnerability in the presence of adverse childhood conditions although other areas not analyzed in this study may also be involved. PMID:24051351

  14. 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

  15. 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

  16. 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

  17. Brain-state–independent neural representation of peripheral stimulation in rat olfactory bulb

    PubMed Central

    Gong, Ling; Xu, Fuqiang

    2011-01-01

    It is critical for normal brains to perceive the external world precisely and accurately under ever-changing operational conditions, yet the mechanisms underlying this fundamental brain function in the sensory systems are poorly understood. To address this issue in the olfactory system, we investigated the responses of olfactory bulbs to odor stimulations under different brain states manipulated by anesthesia levels. Our results revealed that in two brain states, where the spontaneous baseline activities differed about twofold based on the local field potential (LFP) signals, the levels of neural activities reached after the same odor stimulation had no significant difference. This phenomenon was independent of anesthetics (pentobarbital or chloral hydrate), stimulating odorants (ethyl propionate, ethyl butyrate, ethyl valerate, amyl acetate, n-heptanal, or 2-heptanone), odor concentrations, and recording sites (the mitral or granular cell layers) for LFPs in three frequency bands (12–32 Hz, 33–64 Hz, and 65–90 Hz) and for multiunit activities. Furthermore, the activity patterns of the same stimulation under these two brain states were highly similar at both LFP and multiunit levels. These converging results argue the existence of mechanisms in the olfactory bulbs that ensure the delivery of peripheral olfactory information to higher olfactory centers with high fidelity under different brain states. PMID:21321196

  18. 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

  19. 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

  20. GABA-mediated regulation of the activity-dependent olfactory bulb dopaminergic phenotype

    PubMed Central

    Akiba, Yosuke; Sasaki, Hayato; Huerta, Patricio T.; Estevez, Alvaro G.; Baker, Harriet; Cave, John W.

    2009-01-01

    Gamma-amino-butyric acid (GABA) regulates the proliferation and migration of olfactory bulb (OB) interneuron progenitors derived from the subventricular zone (SVZ), but the role of GABA in the differentiation of these progenitors has been largely unexplored. This study examined the role of GABA in the differentiation of OB dopaminergic interneurons using neonatal forebrain organotypic slice cultures prepared from transgenic mice expressing GFP under the control of the tyrosine hydroxylase (Th) gene promoter (ThGFP). KCl-mediated depolarization of the slices induced ThGFP expression. The addition of GABA to the depolarized slices further increased GFP fluorescence by inducing ThGFP expression in an additional set of periglomerular cells. These findings showed that GABA promoted differentiation of SVZ-derived OB dopaminergic interneurons and suggested that GABA indirectly regulated Th expression and OB dopaminergic neuron differentiation through an acceleration of the maturation rate for the dopaminergic progenitors. Additional studies revealed that the effect of GABA on ThGFP expression required activation of L- and P/Q-type Ca+2 channels as well as GABAA and GABAB receptors. These voltage-gated Ca+2 channels and GABA receptors have previously been shown to be required for the co-expressed GABAergic phenotype in the OB interneurons. Together, these findings suggest that Th expression and the differentiation of OB dopaminergic interneurons are coupled to the co-expressed GABAergic phenotype, and demonstrate a novel role for GABA in neurogenesis. PMID:19301430

  1. The impact of adult neurogenesis on olfactory bulb circuits and computations.

    PubMed

    Lepousez, Gabriel; Valley, Matthew T; Lledo, Pierre-Marie

    2013-01-01

    Modern neuroscience has demonstrated how the adult brain has the ability to profoundly remodel its neurons in response to changes in external stimuli or internal states. However, adult brain plasticity, although possible throughout life, remains restricted mostly to subcellular levels rather than affecting the entire cell. New neurons are continuously generated in only a few areas of the adult brain-the olfactory bulb and the dentate gyrus-where they integrate into already functioning circuitry. In these regions, adult neurogenesis adds another dimension of plasticity that either complements or is redundant to the classical molecular and cellular mechanisms of plasticity. This review extracts clues regarding the contribution of adult-born neurons to the different circuits of the olfactory bulb and specifically how new neurons participate in existing computations and enable new computational functions. PMID:23190074

  2. 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

  3. 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.

  4. 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

  5. Convergence of FPR-rs3-expressing neurons in the mouse accessory olfactory bulb.

    PubMed

    Dietschi, Quentin; Assens, Alexis; Challet, Ludivine; Carleton, Alan; Rodriguez, Ivan

    2013-09-01

    In the mouse, most members of the FPR receptor family are expressed by vomeronasal sensory neurons. The neural circuitry corresponding to this class of chemical sensors is unknown. Taking advantage of the presence of FPR-rs3 on both vomeronasal dendrites and axonal fibers, we visualized the distribution of sensory cells expressing this member of the FPR family, and their corresponding axonal projections in the olfactory bulb. We found a rostrocaudal gradient of receptor choice frequency in the vomeronasal sensory neuroepithelium, and observed a convergence of FPR-rs3 axons into multiple, linked and deeply located glomeruli. These were homogenously innervated, and spatially restricted to the basal portion of the rostral accessory olfactory bulb. This organization, reminiscent of the one that characterizes axonal projections of V1R-expressing neurons, supports a role played by these receptors in the perception of semiochemicals. PMID:23664818

  6. 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

  7. Reproductive Status Regulates Expression of Sex Steroid and GnRH Receptors in the Olfactory Bulb

    PubMed Central

    Fernald, Russell D.

    2010-01-01

    Neuromodulators including gonadotropin-releasing hormone (GnRH) and sex steroids help integrate an animal's internal physiological state with incoming external cues, and can have profound effects on the processing of behaviorally-relevant information, particularly from the olfactory system. While GnRH and steroid receptors are present in olfactory processing regions across vertebrates, little is known about whether their expression levels change with internal physiological state or external social cues. We used qRT-PCR to measure mRNA levels of two GnRH receptors (GnRH-R1, GnRH-R2), five sex steroid receptors (estrogen receptors: ERα, ERβa, ERβb; androgen receptors: ARα, ARβ), and aromatase in the olfactory bulb of the highly social African cichlid fish Astatotilapia burtoni. We asked whether these receptor levels changed with reproductive condition in females, or with social status, which regulates reproductive capacity in males. Our results reveal that mRNA levels of multiple sex steroid, GnRH receptor subtypes, and aromatase in the olfactory bulb vary with sex, social status in males, and reproductive condition in females, which highlights the potential importance of changing receptor levels in fine-tuning the olfactory system during the reproductive cycle. Further, steroid receptor mRNA levels were positively correlated with circulating steroid levels in males, but negatively correlated in females, suggesting different regulatory control between sexes. These results provide support for the hypothesis that the first-order olfactory relay station is a substrate for both GnRH and sex steroid modulation, and suggest that changes in receptor levels could be an important mechanism for regulating reproductive, social, and seasonal plasticity in olfactory perception observed across vertebrates. PMID:20466023

  8. 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

  9. Sexual dimorphism in the human olfactory bulb: females have more neurons and glial cells than males.

    PubMed

    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

  10. 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

  11. 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

  12. Pattern of olfactory bulb innervation returns after recovery from reversible peripheral deafferentation.

    PubMed

    Cummings, D M; Emge, D K; Small, S L; Margolis, F L

    2000-06-01

    The olfactory epithelium (OE) is unusual in its ability to regenerate and reinnervate its target, the olfactory bulb (OB), after deafferentation. To address the question of whether olfactory receptor neuron (ORN) axons preserve their topographic organization when they reestablish synaptic contact with the OB, the authors examined the pattern of ORN axon reinnervation into the bulb of adult H-OMP-lacZ-6 transgenic mice during and after recovery from chemical deafferentation. In the H-OMP-lacZ-6 mouse strain, lacZ expression is limited to a subset of ORNs that are distributed bilaterally in the OE and project primarily to a few glomeruli in the ventromedial region of the OB. The OE was lesioned by intranasal irrigation with Triton X-100, and the distribution of 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-gal)-stained cells was examined in the OE along with beta-galactosidase-immunoreactive (beta-gal-ir) axonal processes in the OB after short (1 week), intermediate (3 week), and long (6-7 weeks) recovery times. One week after the lesion, immunostaining for beta-gal and olfactory marker protein was virtually eliminated in the bulb. After 3 weeks of recovery, beta-gal-containing axons appeared to target many of the same locations innervated in bulbs of unlesioned mice. The region that received the highest density of axonal innervation in controls, however, contained only a few processes at that time. After 6-7 week recovery periods, the pattern of X-gal staining in the OE and beta-gal-ir axons in the OB closely resembled that of unlesioned mice. These results demonstrate that the topographic distribution of ORNs in the OE and the pattern of axon innervation in the OB can be reconstituted after chemical deafferentation. PMID:10813792

  13. Postmitotic, postmigrational expression of tyrosine hydroxylase in olfactory bulb dopaminergic neurons.

    PubMed

    McLean, J H; Shipley, M T

    1988-10-01

    The developmental expression of tyrosine hydroxylase (TOH) was studied in a large, specific population of dopaminergic (DA) neurons in the main olfactory bulb (MOB) of the rat. These DA neurons comprise an anatomically distinctive population that has been well characterized in the adult hamster (Davis and Macrides, 1983) and rat (Halasz et al., 1981; Baker et al., 1983, 1984). We addressed a basic question in developmental neurobiology: What factors regulate the expression of neuronal transmitter phenotype during development? Olfactory bulb DA neurons are born in the ventricular and subependymal zones and migrate through all intervening layers to the most superficial layer in the bulb (Altman, 1969; Bayer, 1983). The time of TOH expression in these neurons was determined using immunohistochemistry and light microscopic image-analysis techniques. The results indicate that TOH phenotype is not expressed when the cells are born in the subependymal zone nor during their migration to the periglomerular region but only after they reached their final destination, the glomerular layer. This suggests that epigenetic factors associated with the glomeruli initiate the expression of the key transmitter synthesizing enzyme in these neurons. Primary olfactory neurons in the nasal epithelium project exclusively to glomeruli of the MOB; removal of this input in adult rats (Kawano and Margolis, 1982; Baker et al., 1983, 1984), mice (Nadi et al., 1981; Baker et al., 1983), dogs (Nadi et al., 1981), and hamsters (Kream et al., 1984) appears to down-regulate the expression of the TOH in periglomerular cells. The present results suggested that the input from the primary olfactory nerve is also necessary for the initial expression of the TOH phenotype. In support of this notion, we found that lesions of the olfactory nerve during the first postnatal week caused a significant reduction in the number of TOH-positive juxtaglomerular neurons in the following weeks. Thus, the olfactory nerve

  14. 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

  15. Spontaneous and neurally evoked release of labelled noradrenaline from rabbit olfactory bulbs in vivo

    PubMed Central

    Brenells, Ann B.

    1974-01-01

    1. Rabbit olfactory bulbs were labelled with either [3H]noradrenaline (NA) and [14C]urea, or [14C]NA and [3H]inulin. The labelled substances released were collected by a modified cortical cup technique and estimated by liquid scintillation spectrometry. 2. In many experiments only total radioactivity originating from labelled NA was measured. In such cases the term NA radioactivity is used. 3. The spontaneous release of both NA radioactivity and marker radioactivity followed a multiphasic course. After 140 min the rate of efflux of NA radioactivity was significantly slower than that of the labelled marker. 4. Stimulation of one medial olfactory tract, one lateral olfactory tract or the surface of one bulb resulted in a selective increase in release of NA radioactivity. The size of the increase was dependent on the intensity, frequency and duration of stimulation. 5. There was a characteristic delay in the increased release of NA radioactivity following electrical stimulation. Acute lesioning of the olfactory tracts caudal to the stimulating electrode not only abolished this delay, but also resulted in a larger increase in release following stimulation. 6. The radioactivity attributable to unchanged NA was initially 91%, but decreased to 66% after 4½ hr of sample collection. Stimulation did not affect significantly the relative amounts of NA and metabolites released. 7. Replacement of calcium in the Krebs solution by magnesium did not affect measurably the spontaneous release of NA radioactivity. However, after 1 hr; stimulation failed to increase the efflux of NA radioactivity. 8. It is suggested that the results provide further evidence for a role for NA in synaptic transmission in the olfactory bulbs. PMID:4424430

  16. 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

  17. Cholecystokinin: An Excitatory Modulator of Mitral/Tufted Cells in the Mouse Olfactory Bulb

    PubMed Central

    Ma, Jie; Dankulich-Nagrudny, Luba; Lowe, Graeme

    2013-01-01

    Cholecystokinin (CCK) is widely distributed in the brain as a sulfated octapeptide (CCK-8S). In the olfactory bulb, CCK-8S is concentrated in two laminae: an infraglomerular band in the external plexiform layer, and an inframitral band in the internal plexiform layer (IPL), corresponding to somata and terminals of superficial tufted cells with intrabulbar projections linking duplicate glomerular maps of olfactory receptors. The physiological role of CCK in this circuit is unknown. We made patch clamp recordings of CCK effects on mitral cell spike activity in mouse olfactory bulb slices, and applied immunohistochemistry to localize CCKB receptors. In cell-attached recordings, mitral cells responded to 300 nM –1 µM CCK-8S by spike excitation, suppression, or mixed excitation-suppression. Antagonists of GABAA and ionotropic glutamate receptors blocked suppression, but excitation persisted. Whole-cell recordings revealed that excitation was mediated by a slow inward current, and suppression by spike inactivation or inhibitory synaptic input. Similar responses were elicited by the CCKB receptor-selective agonist CCK-4 (1 µM). Excitation was less frequent but still occurred when CCKB receptors were blocked by LY225910, or disrupted in CCKB knockout mice, and was also observed in CCKA knockouts. CCKB receptor immunoreactivity was detected on mitral and superficial tufted cells, colocalized with Tbx21, and was absent from granule cells and the IPL. Our data indicate that CCK excites mitral cells postsynaptically, via both CCKA and CCKB receptors. We hypothesize that extrasynaptic CCK released from tufted cell terminals in the IPL may diffuse to and directly excite mitral cell bodies, creating a positive feedback loop that can amplify output from pairs of glomeruli receiving sensory inputs encoded by the same olfactory receptor. Dynamic plasticity of intrabulbar projections suggests that this could be an experience-dependent amplification mechanism for tuning and

  18. 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

  19. Newborn Interneurons in the Accessory Olfactory Bulb Promote Mate Recognition in Female Mice

    PubMed Central

    Oboti, Livio; Schellino, Roberta; Giachino, Claudio; Chamero, Pablo; Pyrski, Martina; Leinders-Zufall, Trese; Zufall, Frank; Fasolo, Aldo; Peretto, Paolo

    2011-01-01

    In the olfactory bulb of adult rodents, local interneurons are constantly replaced by immature precursors derived from the subventricular zone. Whether any olfactory sensory process specifically relies on this cell renewal remains largely unclear. By using the well known model of mating-induced imprinting to avoid pregnancy block, which requires accessory olfactory bulb (AOB) function, we demonstrate that this olfactory memory formation critically depends on the presence of newborn granule neurons in this brain region. We show that, in adult female mice, exposure to the male urine compounds involved in mate recognition increases the number of new granule cells surviving in the AOB. This process is modulated by male signals sensed through the vomeronasal organ and, in turn, changes the activity of the downstream amygdaloid and hypothalamic nuclei involved in the pregnancy block response. Chemical depletion of newly generated bulbar interneurons causes strong impairment in mate recognition, thus resulting in a high pregnancy failure rate to familiar mating male odors. Taken together, our results indicate that adult neurogenesis is essential for specific brain functions such as persistent odor learning and mate recognition. PMID:21994486

  20. Similar rate of information transfer on stimulus intensity in accessory and main olfactory bulb output neurons.

    PubMed

    Noguchi, Tomohiro; Sasajima, Hitoshi; Miyazono, Sadaharu; Kashiwayanagi, Makoto

    2014-07-25

    Recently, evidence has accumulated that the vomeronasal system cooperates with the main olfactory system to process volatile cues that regulate the animal's behavior. This is contradictory to the traditional view that the vomeronasal system is quite different from the main olfactory system in the time scale of information processing. Particularly, the firing rate of mitral/tufted cells in the accessory olfactory bulb (MTAOB) is known to be significantly lower than that of mitral cells in the main olfactory bulb (MCMOB). To address this question of whether the low-frequency firing in MTAOB carries less information than the high-frequency firing in MCMOB in the early stages of stimulation, we compared MTAOB and MCMOB for their firing mechanisms and information transfer characteristics. A model computation demonstrated that the inherent channel kinetics of MTAOB was responsible for their firing at a lower frequency than MCMOB. Nevertheless, our analysis suggested that MTAOB were comparable to MCMOB in both the amount and speed of information transfer about depolarizing current intensity immediately after current injection onset (<200ms). Our results support a hypothesis of simultaneous processing of common cues in both systems. PMID:24909616

  1. Habituation of glomerular responses in the olfactory bulb following prolonged odor stimulation reflects reduced peripheral input

    PubMed Central

    Ogg, M. Cameron; Bendahamane, Mounir; Fletcher, Max L.

    2015-01-01

    Following prolonged odor stimulation, output from olfactory bulb (OB) mitral/tufted (M/T) cells is decreased in response to subsequent olfactory stimulation. Currently, it is unclear if this decrease is a function of adaptation of peripheral olfactory sensory neuron (OSN) responses or reflects depression of bulb circuits. We used wide-field calcium imaging in anesthetized transgenic GCaMP2 mice to compare excitatory glomerular layer odor responses before and after a 30-s odor stimulation. Significant habituation of subsequent glomerular odor responses to both the same and structurally similar odorants was detected with our protocol. To test whether depression of OSN terminals contributed to this habituation, olfactory nerve layer (ON) stimulation was used to drive glomerular layer responses in the absence of peripheral odor activation of the OSNs. Following odor habituation, in contrast to odor-evoked glomerular responses, ON stimulation-evoked glomerular responses were not habituated. The difference in response between odor and electrical stimulation following odor habituation provides evidence that odor response reductions measured in the glomerular layer of the OB are most likely the result of OSN adaptation processes taking place in the periphery. PMID:26441516

  2. BDNF over-expression increases olfactory bulb granule cell dendritic spine density in vivo.

    PubMed

    McDole, B; Isgor, C; Pare, C; Guthrie, K

    2015-09-24

    Olfactory bulb granule cells (GCs) are axon-less, inhibitory interneurons that regulate the activity of the excitatory output neurons, the mitral and tufted cells, through reciprocal dendrodendritic synapses located on GC spines. These contacts are established in the distal apical dendritic compartment, while GC basal dendrites and more proximal apical segments bear spines that receive glutamatergic inputs from the olfactory cortices. This synaptic connectivity is vital to olfactory circuit function and is remodeled during development, and in response to changes in sensory activity and lifelong GC neurogenesis. Manipulations that alter levels of the neurotrophin brain-derived neurotrophic factor (BDNF) in vivo have significant effects on dendritic spine morphology, maintenance and activity-dependent plasticity for a variety of CNS neurons, yet little is known regarding BDNF effects on bulb GC spine maturation or maintenance. Here we show that, in vivo, sustained bulbar over-expression of BDNF in transgenic mice produces a marked increase in GC spine density that includes an increase in mature spines on their apical dendrites. Morphometric analysis demonstrated that changes in spine density were most notable in the distal and proximal apical domains, indicating that multiple excitatory inputs are potentially modified by BDNF. Our results indicate that increased levels of endogenous BDNF can promote the maturation and/or maintenance of dendritic spines on GCs, suggesting a role for this factor in modulating GC functional connectivity within adult olfactory circuitry. PMID:26211445

  3. 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

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

    PubMed

    Gschwend, Olivier; Abraham, Nixon M; Lagier, Samuel; Begnaud, Frédéric; Rodriguez, Ivan; Carleton, Alan

    2015-10-01

    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. We found that overlapping odor-evoked input patterns to the mouse olfactory bulb (OB) were dynamically reformatted in the network on the timescale of a single breath, giving rise to separated patterns of activity in an ensemble of output neurons, mitral/tufted (M/T) cells. Notably, the extent of pattern separation in M/T assemblies predicted 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 stimulus distinction, a process that is sculpted by synaptic inhibition. PMID:26301325

  5. Olfactory Bulb Glomerular NMDA Receptors Mediate Olfactory Nerve Potentiation and Odor Preference Learning in the Neonate Rat

    PubMed Central

    Harley, Carolyn W.; Yuan, Qi

    2012-01-01

    Rat pup odor preference learning follows pairing of bulbar beta-adrenoceptor activation with olfactory input. We hypothesize that NMDA receptor (NMDAR)-mediated olfactory input to mitral cells is enhanced during training, such that increased calcium facilitates and shapes the critical cAMP pattern. Here, we demonstrate, in vitro, that olfactory nerve stimulation, at sniffing frequencies, paired with beta-adrenoceptor activation, potentiates olfactory nerve-evoked mitral cell firing. This potentiation is blocked by a NMDAR antagonist and by increased inhibition. Glomerular dishinhibtion also induces NMDAR-sensitive potentiation. In vivo, in parallel, behavioral learning is prevented by glomerular infusion of an NMDAR antagonist or a GABAA receptor agonist. A glomerular GABAA receptor antagonist paired with odor can induce NMDAR-dependent learning. The NMDA GluN1 subunit is phosphorylated in odor-specific glomeruli within 5 min of training suggesting early activation, and enhanced calcium entry, during acquisition. The GluN1 subunit is down-regulated 3 h after learning; and at 24 h post-training the GluN2B subunit is down-regulated. These events may assist memory stability. Ex vivo experiments using bulbs from trained rat pups reveal an increase in the AMPA/NMDA EPSC ratio post-training, consistent with an increase in AMPA receptor insertion and/or the decrease in NMDAR subunits. These results support a model of a cAMP/NMDA interaction in generating rat pup odor preference learning. PMID:22496886

  6. Intraglomerular lateral inhibition promotes spike timing variability in principal neurons of the olfactory bulb.

    PubMed

    Najac, Marion; Sanz Diez, Alvaro; Kumar, Arvind; Benito, Nuria; Charpak, Serge; De Saint Jan, Didier

    2015-03-11

    The activity of mitral and tufted cells, the principal neurons of the olfactory bulb, is modulated by several classes of interneurons. Among them, diverse periglomerular (PG) cell types interact with the apical dendrites of mitral and tufted cells inside glomeruli at the first stage of olfactory processing. We used paired recording in olfactory bulb slices and two-photon targeted patch-clamp recording in vivo to characterize the properties and connections of a genetically identified population of PG cells expressing enhanced yellow fluorescent protein (EYFP) under the control of the Kv3.1 potassium channel promoter. Kv3.1-EYFP(+) PG cells are axonless and monoglomerular neurons that constitute ∼30% of all PG cells and include calbindin-expressing neurons. They respond to an olfactory nerve stimulation with a short barrage of excitatory inputs mediated by mitral, tufted, and external tufted cells, and, in turn, they indiscriminately release GABA onto principal neurons. They are activated by even the weakest olfactory nerve input or by the discharge of a single principal neuron in slices and at each respiration cycle in anesthetized mice. They participate in a fast-onset intraglomerular lateral inhibition between principal neurons from the same glomerulus, a circuit that reduces the firing rate and promotes spike timing variability in mitral cells. Recordings in other PG cell subtypes suggest that this pathway predominates in generating glomerular inhibition. Intraglomerular lateral inhibition may play a key role in olfactory processing by reducing the similarity of principal cells discharge in response to the same incoming input. PMID:25762678

  7. 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

  8. Extracellular glutamate level and NMDA receptor subunit expression in mouse olfactory bulb following nanoparticle-rich diesel exhaust exposure.

    PubMed

    Win-Shwe, Tin-Tin; Mitsushima, Dai; Yamamoto, Shoji; Fujitani, Yuji; Funabashi, Toshiya; Hirano, Seishiro; Fujimaki, Hidekazu

    2009-08-01

    In this present study, we aimed to investigate the extracellular glutamate level and memory function-related gene expression in the mouse olfactory bulb after exposure of the animals to nanoparticle-rich diesel exhaust (NRDE) with or without bacterial cell wall component. Lipoteichoic acid (LTA), a cell wall component derived from Staphylococcus aureus, was used to induce systemic inflammation. Male BALB/c mice were exposed to clean air (particle concentration, 4.58 microg/m(3)) or NRDE (148.86 microg/m(3)) 5 h per day on 5 consecutive days of the week for 4 wk with or without weekly intraperitoneal injection of LTA. We examined the extracellular glutamate levels in the olfactory bulb using in vivo microdialysis and high-performance liquid chromatography assay. Then, we collected the olfactory bulb to examine the expression of N-methyl-D-aspartate (NMDA) receptor subunits (NR1, NR2A, and NR2B) and calcium/calmodulin-dependent protein kinase (CaMK) IV and cyclic AMP response element binding protein (CREB)-1 using real-time reverse-transcription polymerase chain reaction (RT-PCR). NRDE and/or LTA caused significantly increased extracellular glutamate levels in the olfactory bulb of mice. Moreover, the exposure of mice to NRDE upregulates NR1, NR2A, NR2B, and CaMKIV mRNAs in the olfactory bulb, while LTA upregulates only NR2B and CREB1 mRNAs. These findings suggest that NRDE and LTA cause glutamate-induced neurotoxicity separately and accompanied by changes in the expression of NMDA receptor subunits and related kinase and transcription factor in the mouse olfactory bulb. This is the first study to show the correlation between glutamate toxicity and memory function-related gene expressions in the mouse olfactory bulb following exposure to NRDE. PMID:19653804

  9. Slow potentials of the turtle olfactory bulb in response to odor stimulation of the nose.

    PubMed

    Beuerman, R W

    1975-10-24

    Odor stimulation of the nose in the box turtle and the gopher tortoise produced a characteristic series of slow potentials in the olfactory bulb which were referred to as the odor evoked response. When recorded with direct coupling, the odor evoked response had 3 components: wave I, a short duration monophasic event; wave II, a long duration variation in the DC potential; and wave III, an oscillatory potential superimposed on wave II. Waves I and II were negative at bulbar surfaces receiving olfactory input and positive deep within the bulb. This series of potentials could be evoked by 3 methods of odor stimulation: (1) large puffs delivered from odorant test bottles, (2) small puffs delivered from a syringe and (3) continuous flow with concentration and nasal flow rate parameters controlled by an olfactometer. When the odor evoked response was recorded at a bulbar locus, these potentials were seen in response to each stimulation and the amplitudes of each wave were reproducible with the same stimulus. The amplitudes of the 3 waves were compared in the gopher tortoise and differed with the 3 odorants tested--high purity geraniol, technical grade geraniol and amyl acetate. Odorant concentration also directly affected the response amplitudes of all 3 wave components. The amplitudes of waves I and III markedly decreased with closely spaced stimulations recovering to near the initial values when the interstimulus interval was increased severalfold. This series of sensory evoked potentials is considered to reflect the processing of odor information from the olfactory receptors by the olfactory bulb. PMID:1175040

  10. Mitral cells in the olfactory bulb of adult zebrafish (Danio rerio): morphology and distribution.

    PubMed

    Fuller, Cynthia L; Yettaw, Holly K; Byrd, Christine A

    2006-11-10

    The mitral cell is the primary output neuron and central relay in the olfactory bulb of vertebrates. The morphology of these cells has been studied extensively in mammalian systems and to a lesser degree in teleosts. This study uses retrograde tract tracing and other techniques to characterize the morphology and distribution of mitral cells in the olfactory bulb of adult zebrafish, Danio rerio. These output neurons, located primarily in the glomerular layer and superficial internal cell layer, had variable-shaped somata that ranged in size from 4-18 microm in diameter and 31-96 microm2 in cross-sectional area. The mitral cells exhibited two main types of morphologies with regard to their dendrites: the unidendritic morphology was a single primary dendrite with one or more tufts, but multidendritic cells with several dendritic projections also were seen. The axons of these cells projected to either the medial or the lateral olfactory tract and, in general, the location of the cell on the medial or lateral side of the bulb was indicative of the tract to which it would project. Further, this study shows that the majority of zebrafish mitral cells likely innervate a single glomerulus rather than multiple glomeruli. This information is contrary to the multiple innervation pattern suggested for all teleost mitral cells. Our findings suggest that mitral cells in zebrafish may be more similar to mammalian mitral cells than previously believed, despite variation in size and structure. This information provides a revised anatomical framework for olfactory processing studies in this key model system. PMID:16977629

  11. 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. PMID:24760863

  12. Vasoactive Intestinal Polypeptide Mediates Circadian Rhythms in Mammalian Olfactory Bulb and Olfaction

    PubMed Central

    Miller, Jae-eun Kang; Granados-Fuentes, Daniel; Wang, Thomas; Marpegan, Luciano; Holy, Timothy E.

    2014-01-01

    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. PMID:24760863

  13. 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. PMID:10880998

  14. 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

  15. Metabotropic glutamate receptors promote disinhibition of olfactory bulb glomeruli that scales with input strength

    PubMed Central

    Zak, Joseph D.; Whitesell, Jennifer D.

    2014-01-01

    Increasing evidence indicates that the neural circuitry within glomeruli of the olfactory bulb plays a major role in affecting information flow between olfactory sensory neurons (OSNs) and output mitral cells (MCs). Glutamatergic external tufted (ET) cells, located at glomeruli, can act as intermediary cells in excitation between OSNs and MCs, whereas activation of MCs by OSNs is, in turn, suppressed by inhibitory synapses onto ET cells. In this study, we used patch-clamp recordings in rat olfactory bulb slices to examine the function of metabotropic glutamate receptors (mGluRs) in altering these glomerular signaling mechanisms. We found that activation of group II mGluRs profoundly reduced inhibition onto ET cells evoked by OSN stimulation. The mGluRs that mediated disinhibition were located on presynaptic GABAergic periglomerular cells and appeared to be activated by glutamate transients derived from dendrites in glomeruli. In terms of glomerular output, the mGluR-mediated reduction in GABA release led to a robust increase in the number of action potentials evoked by OSN stimulation in both ET cells and MCs. Importantly, however, the enhanced excitation was specific to when a glomerulus was strongly activated by OSN inputs. By being selective for strong vs. weak glomerular activation, mGluR-mediated disinhibition provides a mechanism to enhance the contrast in odor signals that activate OSN inputs into a single glomerulus at varying intensities. PMID:25552635

  16. 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

  17. Dual origins of the mammalian accessory olfactory bulb revealed by an evolutionarily conserved migratory stream.

    PubMed

    Huilgol, Dhananjay; Udin, Susan; Shimogori, Tomomi; Saha, Bhaskar; Roy, Achira; Aizawa, Shinichi; Hevner, Robert F; Meyer, Gundela; Ohshima, Toshio; Pleasure, Samuel J; Zhao, Yangu; Tole, Shubha

    2013-02-01

    The accessory olfactory bulb (AOB) is a critical olfactory structure that has been implicated in mediating social behavior. It receives input from the vomeronasal organ and projects to targets in the amygdaloid complex. Its anterior and posterior components (aAOB and pAOB) display molecular, connectional and functional segregation in processing reproductive and defensive and aggressive behaviors, respectively. We observed a dichotomy in the development of the projection neurons of the aAOB and pAOB in mice. We found that they had distinct sites of origin and that different regulatory molecules were required for their specification and migration. aAOB neurons arose locally in the rostral telencephalon, similar to main olfactory bulb neurons. In contrast, pAOB neurons arose caudally, from the neuroepithelium of the diencephalic-telencephalic boundary, from which they migrated rostrally to reach their destination. This unusual origin and migration is conserved in Xenopus, providing an insight into the origin of a key component of this system in evolution. PMID:23292680

  18. Goα expression in the vomeronasal organ and olfactory bulb of the tammar wallaby.

    PubMed

    Schneider, Nanette Y; Fletcher, Terrence P; Shaw, Geoff; Renfree, Marilyn B

    2012-07-01

    The vomeronasal organ (VNO) detects pheromones via 2 large families of receptors: vomeronasal receptor 1, associated with the protein Giα2, and vomeronasal receptor 2, associated with Goα. We investigated the distribution of Goα in the developing and adult VNO and adult olfactory bulb of a marsupial, the tammar wallaby. Some cells expressed Goα as early as day 5 postpartum, but by day 30, Goα expressing cells were distributed throughout the receptor epithelium of the VNO. In the adult tammar, Goα appeared to be expressed in sensory neurons whose nuclei were mostly basally located in the vomeronasal receptor epithelium. Goα expressing vomeronasal receptor cells led to all areas of the accessory olfactory bulb (AOB). The lack of regionally restricted projection of the vomeronasal receptor cell type 2 in the tammar was similar to the uniform type, with the crucial difference that the uniform type only shows expression of Giα2 and no expression of Goα. The observed Goα staining pattern suggests that the tammar may have a third accessory olfactory type that could be intermediate to the segregated and uniform types already described. PMID:22383629

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

    PubMed Central

    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

  20. Electrophysiological analysis of mitral cells in the isolated turtle olfactory bulb.

    PubMed

    Mori, K; Nowycky, M C; Shepherd, G M

    1981-05-01

    1. An in vitro preparation of the turtle olfactory bulb has been developed. Electrophysiological properties of mitral cells in the isolated bulb have been analysed with intracellular recordings. 2. Mitral cells have been driven antidromically from the lateral olfactory tract, or activated directly by current injection. Intracellular injections of horseradish peroxidase (HRP) show that turtle mitral cells have long secondary dendrites that extend up to 1800 micrometer from the cell body and reach around half of the bulbar circumference. There are characteristically two primary dendrites, each supplying separate olfactory glomeruli. 3. Using intracellular current pulses, the whole-neurone resistance was found to range from 33 to 107 M omega. The whole-neurone charging transient had a slow time course. The membrane time constant was estimated to be 24-93 msec by the methods of Rall. The electrotonic length of the mitral cell equivalent cylinder was estimated by Rall's methods to be 0.9-1.9. 4. The spikes generated by turtle mitral cells were only partially blocked by tetrodotoxin (TTX) in the bathing medium. The TTX-resistant spikes were enhanced in the presence of tetraethylammonium (TEA), and blocked completely by cobalt. 5. The implications of the electrical properties for impulse generation in turtle mitral cells are discussed. The mitral cells have dendrodendritic synapses onto granule cells, and the TTX-resistant spikes may therefore play an important role in presynaptic transmitter release at these synapses. PMID:7310692

  1. [Activity of glial cells in the olfactory bulb of Niemann-Pick disease type C1 mice].

    PubMed

    Yan, Xin; Qiao, Liang; Yang, En-Hui; Lin, Jun-Tang

    2016-04-25

    To study the pathological mechanisms of Niemann-Pick disease type C1, we observed the changes of activation of glial cells in the olfactory bulb of Npc1 mutant (Npc1(-/-)) mice. The genomic DNA was extracted from mouse tails for genotyping by PCR. Immunofluorescent histochemistry was performed to examine the activation of microglia and astrocytes in the olfactory bulb of Npc1(-/-) mice on postnatal day 30. NeuN, phosphorylated neurofilament (NF), Doublecortin (DCX), CD68 and GFAP were detected by Western blot. The results showed that Npc1 gene mutation strongly increased the activation of astrocytes and microglia in olfactory bulb associated with increased protein levels of CD68 and GFAP. Furthermore, the expression of phosphorylated NF was also significantly increased in the olfactory bulb of Npc1(-/-) mice compared with that in Npc1(+/+) mice. However, DCX expression was significantly reduced. The above results suggest that there are some early changes in the olfactory bulb of Npc1(-/-) mice. PMID:27108900

  2. Processing of odor stimuli by neuronal network models of the olfactory bulb

    NASA Astrophysics Data System (ADS)

    Wick, Stuart; Wiechert, Martin; Riecke, Hermann; Friedrich, Rainer

    2007-03-01

    The space of perceptable odors is high-dimensional and its representation in the various brain structures is still poorly understood. We focus on the olfactory bulb, which constitutes the first processing stage for odor stimuli after they have been sensed by receptor neurons. Experimentally it is found that the correlations between the outputs of the bulb are significantly reduced relative to those of the corresponding inputs, thus enhancing the discriminability of similar odors. We have generated a firing-rate-based network model with parameters derived from experimental data that reproduces decorrelation. Here we use this model to investigate the dependence of stimulus representations on odor concentration. We address the possibility of a change in perceived odor identity with changing concentration and the dependence of odor discriminability on odor concentration. We interpret some of our results within a simple mean-field model for the neural activity.

  3. Cross-linking of atrial natriuretic peptide to binding sites in rat olfactory bulb membranes

    SciTech Connect

    Wildey, G.M.; Glembotski, C.C.

    1986-12-01

    Binding sites for /sup 125/I-atrial natriuretic peptide (ANP)2 in rat olfactory bulb membranes have been studied using pharmacological and biochemical methods. Various unlabeled ANP-related peptides were tested for the ability to inhibit the binding of the radioligand in membrane binding assays. ANP(92-126) and ANP(99-126) were the most potent inhibitors tested, both exhibiting an IC50 value of 0.40 nM. ANP(103-126) and ANP(103-123) were 3 and 70 times less potent, respectively. ANP(111-126) was unable to inhibit the binding of the radioligand at a concentration of 1 microM. Several peptides unrelated to ANP were unable to inhibit the binding of the radioligand to rat olfactory bulb membranes. Membranes labeled with /sup 125/I-ANP were incubated with cross-linking agents and subjected to SDS-PAGE followed by autoradiography. A band possessing an apparent molecular mass of 116 kDa was identified. The labeling of this band was progressively decreased by increasing concentrations of unlabeled ANP(99-126) (IC50 = 0.6 nM) and by several other ANP-related peptides at nanomolar concentrations. For comparison purposes, ANP binding sites in rat aorta membranes were labeled with /sup 125/I-ANP and cross-linked using identical techniques. Three bands possessing molecular masses of 120, 72, and 62 kDa were identified. These results indicate that the ANP binding site in rat olfactory bulb membranes displays pharmacological and biochemical properties similar to peripheral ANP receptors.

  4. Activation of raphe nuclei triggers rapid and distinct effects on parallel olfactory bulb output channels.

    PubMed

    Kapoor, Vikrant; Provost, Allison C; Agarwal, Prateek; Murthy, Venkatesh N

    2016-02-01

    The serotonergic raphe nuclei are involved in regulating brain states over timescales of minutes and hours. We examined more rapid effects of raphe activation on two classes of principal neurons in the mouse olfactory bulb, mitral and tufted cells, which send olfactory information to distinct targets. Brief stimulation of the raphe nuclei led to excitation of tufted cells at rest and potentiation of their odor responses. While mitral cells at rest were also excited by raphe activation, their odor responses were bidirectionally modulated, leading to improved pattern separation of odors. In vitro whole-cell recordings revealed that specific optogenetic activation of raphe axons affected bulbar neurons through dual release of serotonin and glutamate. Therefore, the raphe nuclei, in addition to their role in neuromodulation of brain states, are also involved in fast, sub-second top-down modulation similar to cortical feedback. This modulation can selectively and differentially sensitize or decorrelate distinct output channels. PMID:26752161

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

    PubMed

    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

  6. Activation of raphe nuclei triggers rapid and distinct effects on parallel olfactory bulb output channels

    PubMed Central

    Kapoor, Vikrant; Provost, Allison; Agarwal, Prateek; Murthy, Venkatesh N.

    2015-01-01

    The serotonergic raphe nuclei are involved in regulating brain states over time-scales of minutes and hours. We examined more rapid effects of serotonergic activation on two classes of principal neurons in the mouse olfactory bulb, mitral and tufted cells, which send olfactory information to distinct targets. Brief stimulation of the raphe nuclei led to excitation of tufted cells at rest and potentiation of their odor responses. While mitral cells at rest were also excited by raphe activation, their odor responses were bidirectionally modulated, leading to improved pattern separation of odors. In vitro whole-cell recordings revealed that specific optogenetic activation of raphe axons affected bulbar neurons through dual release of serotonin and glutamate. Therefore, the raphe nuclei, in addition to their role in neuromodulation of brain states, are also involved in fast, sub-second top-down modulation, similar to cortical feedback. This modulation can selectively and differentially sensitize or decorrelate distinct output channels. PMID:26752161

  7. The olfactory bulb theta rhythm follows all frequencies of diaphragmatic respiration in the freely behaving rat

    PubMed Central

    Rojas-Líbano, Daniel; Frederick, Donald E.; Egaña, José I.; Kay, Leslie M.

    2014-01-01

    Sensory-motor relationships are part of the normal operation of sensory systems. Sensing occurs in the context of active sensor movement, which in turn influences sensory processing. We address such a process in the rat olfactory system. Through recordings of the diaphragm electromyogram (EMG), we monitored the motor output of the respiratory circuit involved in sniffing behavior, simultaneously with the local field potential (LFP) of the olfactory bulb (OB) in rats moving freely in a familiar environment, where they display a wide range of respiratory frequencies. We show that the OB LFP represents the sniff cycle with high reliability at every sniff frequency and can therefore be used to study the neural representation of motor drive in a sensory cortex. PMID:24966821

  8. 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

  9. Coding Odorant Concentration Through Activation Timing Between the Medial and Lateral Olfactory Bulb

    PubMed Central

    Zhou, Zhishang; Belluscio, Leonardo

    2012-01-01

    SUMMARY In mammals, each olfactory bulb (OB) contains a pair of mirror-symmetric glomerular maps organized to reflect odorant receptor identity. The functional implication of maintaining these symmetric medial-lateral maps within each OB remains unclear. Here, using in vivo multi-electrode recordings to simultaneously detect odorant-induced activity across the entire OB, we reveal a timing difference in the odorant-evoked onset latencies between the medial and lateral halves. Interestingly, the latencies in the medial and lateral OB decreased at different rates as odorant concentration increased, causing the timing difference between them to also diminish. As a result, output neurons in the medial and lateral OB fired with greater synchrony at higher odorant concentrations. Thus, we propose that temporal differences in activity between the medial and lateral OB can dynamically code odorant concentration, which is subsequently decoded in the olfactory cortex through the integration of synchronous action potentials. PMID:23168258

  10. 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

  11. Short-axon cells in the olfactory bulb: dendrodendritic synaptic interactions.

    PubMed Central

    Getchell, T V; Shepherd, G M

    1975-01-01

    1. In the rabbit olfactory bulb, analysis has been carried out of extracellular unitary responses in the glomerular layer to olfactory nerve volleys. 2. Units in the glomerular layer responded to single volleys with single, double, triple or longer repetitive spike discharges. The shortest initial latencies are consistent with monosynaptic excitation from the olfactory nerves; longer latencies may reflect longer nerve pathways or polysynaptic connexions in the glomerular layer. 3. Like mitral and tufted cells, some glomerular layer units gave evidence of activation by discrete nerve bundles. This correlates with recent anatomical evidence for projections of discrete olfactory nerve bundles to the glomeruli. 4. Facilitation of glomerular layer units took the form of lower spike thresholds and shorter latencies, when testing with paired olfactory nerve volleys of weak strength at relatively short intervals (less than 40 msec). Supression took the form of raised thresholds, longer latencies and briefer repetitive discharges; this was particularly evident with strong volleys at long testing intervals. 5. The early period of facilitation and later period of suppression did not correlate with the recovery cycle of the olfactory nerves; the nerves had an absolute refractory period of approximately 3 msec, relative refractory period of 15-30 msec, and a small supernormal period of several hundred msec or more. 6. The evidence that the facilitation and suppression are mediated by dendrodendritic pathways through the periglomerular short-axon cells is discussed in relation to recent electronmicroscopical studies. The results have implications for similar pathways through short-axon cell dendrites in other parts of the nervous system. PMID:1185673

  12. Reliable sex and strain discrimination in the mouse vomeronasal organ and accessory olfactory bulb.

    PubMed

    Tolokh, Illya I; Fu, Xiaoyan; Holy, Timothy E

    2013-08-21

    Animals modulate their courtship and territorial behaviors in response to olfactory cues produced by other animals. In rodents, detecting these cues is the primary role of the accessory olfactory system (AOS). We sought to systematically investigate the natural stimulus coding logic and robustness in neurons of the first two stages of accessory olfactory processing, the vomeronasal organ (VNO) and accessory olfactory bulb (AOB). We show that firing rate responses of just a few well-chosen mouse VNO or AOB neurons can be used to reliably encode both sex and strain of other mice from cues contained in urine. Additionally, we show that this population code can generalize to new concentrations of stimuli and appears to represent stimulus identity in terms of diverging paths in coding space. Together, the results indicate that firing rate code on the temporal order of seconds is sufficient for accurate classification of pheromonal patterns at different concentrations and may be used by AOS neural circuitry to discriminate among naturally occurring urine stimuli. PMID:23966710

  13. Disruption of Adult Neurogenesis in the Olfactory Bulb Affects Social Interaction but not Maternal Behavior

    PubMed Central

    Feierstein, Claudia E.; Lazarini, Françoise; Wagner, Sebastien; Gabellec, Marie-Madeleine; de Chaumont, Fabrice; Olivo-Marin, Jean-Christophe; Boussin, François D.; Lledo, Pierre-Marie; Gheusi, Gilles

    2010-01-01

    Adult-born neurons arrive to the olfactory bulb (OB) and integrate into the existing circuit throughout life. Despite the prevalence of this phenomenon, its functional impact is still poorly understood. Recent studies point to the importance of newly generated neurons to olfactory learning and memory. Adult neurogenesis is regulated by a variety of factors, notably by instances related to reproductive behavior, such as exposure to mating partners, pregnancy and lactation, and exposure to offspring. To study the contribution of olfactory neurogenesis to maternal behavior and social recognition, here we selectively disrupted OB neurogenesis using focal irradiation of the subventricular zone in adult female mice. We show that reduction of olfactory neurogenesis results in an abnormal social interaction pattern with male, but not female, conspecifics; we suggest that this effect could result from the inability to detect or discriminate male odors and could therefore have implications for the recognition of potential mating partners. Disruption of OB neurogenesis, however, neither impaired maternal-related behaviors, nor did it affect the ability of mothers to discriminate their own progeny from others. PMID:21160552

  14. 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

  15. 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

  16. Context-driven activation of odor representations in the absence of olfactory stimuli in the olfactory bulb and piriform cortex

    PubMed Central

    Mandairon, Nathalie; Kermen, Florence; Charpentier, Caroline; Sacquet, Joelle; Linster, Christiane; Didier, Anne

    2014-01-01

    Sensory neural activity is highly context dependent and shaped by experience and expectation. In the olfactory bulb (OB), the first cerebral relay of olfactory processing, responses to odorants are shaped by previous experiences including contextual information thanks to strong feedback connections. In the present experiment, mice were conditioned to associate an odorant with a visual context and were then exposed to the visual context alone. We found that the visual context alone elicited exploration of the odor port similar to that elicited by the stimulus when it was initially presented. In the OB, the visual context alone elicited a neural activation pattern, assessed by mapping the expression of the immediate early gene zif268 (egr-1) that was highly similar to that evoked by the conditioned odorant, but not other odorants. This OB activation was processed by olfactory network as it was transmitted to the piriform cortex. Interestingly, a novel context abolished neural and behavioral responses. In addition, the neural representation in response to the context was dependent on top-down inputs, suggesting that context-dependent representation is initiated in cortex. Modeling of the experimental data suggests that odor representations are stored in cortical networks, reactivated by the context and activate bulbar representations. Activation of the OB and the associated behavioral response in the absence of physical stimulus showed that mice are capable of internal representations of sensory stimuli. The similarity of activation patterns induced by imaged and the corresponding physical stimulus, triggered only by the relevant context provides evidence for an odor-specific internal representation. PMID:24808838

  17. Control of on/off glomerular signaling by a local GABAergic microcircuit in the olfactory bulb

    PubMed Central

    Gire, David H.; Schoppa, Nathan E.

    2009-01-01

    Odors are coded at the input-level of the olfactory bulb by a spatial map of activated glomeruli, reflecting different odorant receptors (ORs) stimulated in the nose. Here we examined the function of local synaptic processing within glomeruli in transforming these input patterns into an output for the bulb, using patch-clamp recordings and calcium imaging in rat bulb slices. Two types of transformations were observed at glomeruli, the first of which produced a bimodal, “on/off” glomerular signal that varied probabilistically depending on ORN input levels. The bimodal response-behavior was seen in glomerular synaptic responses, as well as in action potential (“spike”)-firing, wherein all mitral cells affiliated with a glomerulus either engaged in prolonged spike bursts or did not spike at all. In addition, evidence was obtained that GABAergic periglomerular (PG) cells that surround a glomerulus can prevent activation of a glomerulus through inhibitory inputs targeted onto excitatory external tufted cells. The path of PG cell activation appeared to be confined to one glomerulus, such that ORNs at one glomerulus initiated inhibition of the same glomerulus. The observed glomerular “self-inhibition” provides a mechanism of filtering odor signals that would be an alternative to commonly-proposed mechanisms of lateral inhibition between OR-specific glomeruli. In this case, selective suppression of weak odor signals could be achieved based on the difference in the input resistance of PG cells versus excitatory neurons at a glomerulus. PMID:19864558

  18. Glomerular input patterns in the mouse olfactory bulb evoked by retronasal odor stimuli

    PubMed Central

    2013-01-01

    Background Odorant stimuli can access the olfactory epithelium either orthonasally, by inhalation through the external nares, or retronasally by reverse airflow from the oral cavity. There is evidence that odors perceived through these two routes can differ in quality and intensity. We were curious whether such differences might potentially have a neural basis in the peripheral mechanisms of odor coding. To explore this possibility, we compared olfactory receptor input to glomeruli in the dorsal olfactory bulb evoked by orthonasal and retronasal stimulation. Maps of glomerular response were acquired by optical imaging of transgenic mice expressing synaptopHluorin (spH), a fluorescent reporter of presynaptic activity, in olfactory nerve terminals. Results We found that retronasally delivered odorants were able to activate inputs to multiple glomeruli in the dorsal olfactory bulb. The retronasal responses were smaller than orthonasal responses to odorants delivered at comparable concentrations and flow rates, and they displayed higher thresholds and right-shifted dose–response curves. Glomerular maps of orthonasal and retronasal responses were usually well overlapped, with fewer total numbers of glomeruli in retronasal maps. However, maps at threshold could be quite distinct with little overlap. Retronasal responses were also more narrowly tuned to homologous series of aliphatic odorants of varying carbon chain length, with longer chain, more hydrophobic compounds evoking little or no response at comparable vapor levels. Conclusions Several features of retronasal olfaction are possibly referable to the observed properties of glomerular odorant responses. The finding that retronasal responses are weaker and sparser than orthonasal responses is consistent with psychophysical studies showing lower sensitivity for retronasal olfaction in threshold and suprathreshold tests. The similarity and overlap of orthonasal and retronasal odor maps at suprathreshold

  19. Neuropilin-2 is required for the proper targeting of ventral glomeruli in the mouse olfactory bulb.

    PubMed

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

    2010-07-01

    Recent evidence shows that olfactory sensory neurons expressing a given odorant receptor (OR) are not necessarily confined to one of four zones, rather arranged in an overlapping manner in the olfactory epithelium (OE). In this study, in situ hybridization of OE sections with the OR probes indicated that the OR genes, the mRNAs of which were detected in an array of glomeruli on olfactory bulb (OB) along the anterodorsal/posteroventral (AD/PV) axis, are expressed in subareal zones within the most ventral zone, zone 4, along the dorsomedial/ventrolateral (DM/VL) axis. We also found that Neuropilin-2 (Nrp2) is expressed in a DM-low to VL-high gradient within zone 4 of OE. Furthermore, in Nrp2 mutant mice, we observed multiple glomeruli for zone 4 ORs in OB. These results suggest that the graded expression of Nrp2 in OE is required for the proper targeting of ventral glomeruli along the AD/PV axis in OB. PMID:20363325

  20. Perceptual stability during dramatic changes in olfactory bulb activation maps and dramatic declines in activation amplitudes

    PubMed Central

    Homma, R.; Cohen, L. B.; Kosmidis, E. K.; Youngentob, S. L.

    2009-01-01

    We compared the concentration dependence of the ability of rats to identify odorants with the calcium signals in the nerve terminals of the olfactory receptor neurons. Although identification performance decreased with concentrations both above and below the training stimuli it remained well above random at all concentrations tested (between 0.0006% and 35% of saturated vapor). In contrast, the calcium signals in the same awake animals were much smaller than their maximum values at odorant concentrations less than 1% of saturated vapor. In addition, maps of activated glomeruli changed dramatically as odorant concentration was reduced. Thus perceptual stability exists in the face of dramatic changes in both the amplitude and the maps of the input to the olfactory bulb. The data for the concentration dependence of the response of the most sensitive glomeruli for each of five odorants was fitted with a Michaelis-Menten (Hill) equation. The fitted curves were extrapolated to odorant concentrations several orders of magnitude lower the smallest observed signals and suggest that the calcium response at low odorant concentrations is more than 1000 times smaller than the response at saturating odorant concentrations. We speculate that only a few spikes in olfactory sensory neurons may be sufficient for correct odorant identification. PMID:19291227

  1. 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

  2. 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

  3. 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

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

    PubMed

    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

  5. 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...

  6. 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

  7. Streptococcus pneumoniae infection regulates expression of neurotrophic factors in the olfactory bulb and cultured olfactory ensheathing cells.

    PubMed

    Ruiz-Mendoza, S; Macedo-Ramos, H; Santos, F A; Quadros-de-Souza, L C; Paiva, M M; Pinto, T C A; Teixeira, L M; Baetas-da-Cruz, W

    2016-03-11

    Streptococcus pneumoniae is the causative agent of numerous diseases including severe invasive infections such as bacteremia and meningitis. It has been previously shown that strains of S. pneumoniae that are unable to survive in the bloodstream may colonize the CNS. However, information on cellular components and pathways involved in the neurotropism of these strains is still scarce. The olfactory system is a specialized tissue in which olfactory receptor neurons (ORNs) are interfacing with the external environment through several microvilli. Olfactory ensheathing cells (OECs) which also form the glial limiting membrane at the surface of the olfactory bulb (OB) are the only cells that ensheathe the ORNs axons. Since previous data from our group showed that OECs may harbor S. pneumoniae, we decided to test whether infection of the OB or OEC cultures modulates the expression levels of neurotrophic factor's mRNA and its putative effects on the activation and viability of microglia. We observed that neurotrophin-3 (NT-3) and glial cell-line-derived neurotrophic factor (GDNF) expression was significantly higher in the OB from uninfected mice than in infected mice. A similar result was observed when we infected OEC cultures. Brain-derived neurotrophic factor (BNDF) expression was significantly lower in the OB from infected mice than in uninfected mice. In contrast, in vitro infection of OECs resulted in a significant increase of BDNF mRNA expression. An upregulation of high-mobility group box 1 (HMGB1) expression was observed in both OB and OEC cultures infected with S. pneumoniae. Moreover, we found that conditioned medium from infected OEC cultures induced the expression of the pro-apoptotic protein cleaved-caspase-3 and an apparently continuous nuclear factor-kappa B (NF-κB) p65 activation in the N13 microglia. Altogether, our data suggest the possible existence of an OEC-pathogen molecular interface, through which the OECs could interfere on the activation and

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

    PubMed

    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 microg) intranasally. Six hours after the nanoparticle instillation, the mice were intraperitoneally injected with normal saline or 50 mug 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 in the

  9. 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

  10. Physical limits to autofluorescence signals in vivo recordings in the rat olfactory bulb: a Monte Carlo study

    NASA Astrophysics Data System (ADS)

    L'Heureux, B.; Gurden, H.; Pinot, L.; Mastrippolito, R.; Lefebvre, F.; Lanièce, P.; Pain, F.

    2007-07-01

    Understanding the cellular mechanisms of energy supply to neurons following physiological activation is still challenging and has strong implications to the interpretation of clinical functional images based on metabolic signals such as Blood Oxygen Level Dependent Magnetic Resonance Imaging or 18F-Fluorodexoy-Glucose Positron Emission Tomography. Intrinsic Optical Signal Imaging provides with high spatio temporal resolution in vivo imaging in the anaesthetized rat. In that context, intrinsic signals are mainly related to changes in the optical absorption of haemoglobin depending on its oxygenation state. This technique has been validated for imaging of the rat olfactory bulb, providing with maps of the actived olfactory glomeruli, the functional modules involved in the first step of olfactory coding. A complementary approach would be autofluorescence imaging relying on the fluorescence properties of endogenous Flavin Adenine Dinucleotide (FAD) or Nicotinamide Adenine Dinucleotide (NADH) both involved in intracellular metabolic pathways. The purpose of the present study was to investigate the feasibility of in vivo autofluorescence imaging in the rat olfactory bulb. We performed standard Monte Carlo simulations of photons scattering and absorption at the excitation and emission wavelengths of FAD and NADH fluorescence. Characterization of the fluorescence distribution in the glomerulus, effect of hemoglobin absorption at the excitation and absorption wavelengths as well as the effect of the blurring due to photon scattering and the depth of focus of the optical apparatus have been studied. Finally, optimal experimental parameters are proposed to achieve in vivo validation of the technique in the rat olfactory bulb.

  11. 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

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

    PubMed Central

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

    2014-01-01

    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

  13. 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

  14. Temporal Structure of Receptor Neuron Input to the Olfactory Bulb Imaged in Behaving Rats

    PubMed Central

    Carey, Ryan M.; Verhagen, Justus V.; Wesson, Daniel W.; Pírez, Nicolás; Wachowiak, Matt

    2009-01-01

    The dynamics of sensory input to the nervous system play a critical role in shaping higher-level processing. In the olfactory system, the dynamics of input from olfactory receptor neurons (ORNs) are poorly characterized and depend on multiple factors, including respiration-driven airflow through the nasal cavity, odorant sorption kinetics, receptor–ligand interactions between odorant and receptor, and the electrophysiological properties of ORNs. Here, we provide a detailed characterization of the temporal organization of ORN input to the mammalian olfactory bulb (OB) during natural respiration, using calcium imaging to monitor ORN input to the OB in awake, head-fixed rats expressing odor-guided behaviors. We report several key findings. First, across a population of homotypic ORNs, each inhalation of odorant evokes a burst of action potentials having a rise time of about 80 ms and a duration of about 100 ms. This rise time indicates a relatively slow, progressive increase in ORN activation as odorant flows through the nasal cavity. Second, the dynamics of ORN input differ among glomeruli and for different odorants and concentrations, but remain reliable across successive inhalations. Third, inhalation alone (in the absence of odorant) evokes ORN input to a significant fraction of OB glomeruli. Finally, high-frequency sniffing of odorant strongly reduces the temporal coupling between ORN inputs and the respiratory cycle. These results suggest that the dynamics of sensory input to the olfactory system may play a role in coding odor information and that, in the awake animal, strategies for processing odor information may change as a function of sampling behavior. PMID:19091924

  15. β3GnT2 null mice exhibit defective accessory olfactory bulb innervation.

    PubMed

    Henion, Timothy R; Madany, Pasil A; Faden, Ashley A; Schwarting, Gerald A

    2013-01-01

    Vomeronasal sensory neurons (VSNs) extend axons to the accessory olfactory bulb (AOB) where they form synaptic connections that relay pheromone signals to the brain. The projections of apical and basal VSNs segregate in the AOB into anterior (aAOB) and posterior (pAOB) compartments. Although some aspects of this organization exhibit fundamental similarities with the main olfactory system, the mechanisms that regulate mammalian vomeronasal targeting are not as well understood. In the olfactory epithelium (OE), the glycosyltransferase β3GnT2 maintains expression of axon guidance cues required for proper glomerular positioning and neuronal survival. We show here that β3GnT2 also regulates guidance and adhesion molecule expression in the vomeronasal system in ways that are partially distinct from the OE. In wildtype mice, ephrinA5(+) axons project to stereotypic subdomains in both the aAOB and pAOB compartments. This pattern is dramatically altered in β3GnT2(-/-) mice, where ephrinA5 is upregulated exclusively on aAOB axons. Despite this, apical and basal VSN projections remain strictly segregated in the null AOB, although some V2r1b axons that normally project to the pAOB inappropriately innervate the anterior compartment. These fibers appear to arise from ectopic expression of V2r1b receptors in a subset of apical VSNs. The homotypic adhesion molecules Kirrel2 and OCAM that facilitate axon segregation and glomerular compartmentalization in the main olfactory bulb are ablated in the β3GnT2(-/-) aAOB. This loss is accompanied by a two-fold increase in the total number of V2r1b glomeruli and a failure to form morphologically distinct glomeruli in the anterior compartment. These results identify a novel function for β3GnT2 glycosylation in maintaining expression of layer-specific vomeronasal receptors, as well as adhesion molecules required for proper AOB glomerular formation. PMID:23006775

  16. 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. PMID:9182799

  17. Decomposition of a mixture of signals in a model of the olfactory bulb.

    PubMed

    Hendin, O; Horn, D; Hopfield, J J

    1994-06-21

    We describe models for the olfactory bulb which perform separation and decomposition of mixed odor inputs from different sources. The odors are unknown to the system; hence this is an analog and extension of the engineering problem of blind separation of signals. The separation process makes use of the different temporal fluctuations of the input odors which occur under natural conditions. We discuss two possibilities, one relying on a specific architecture connecting modules with the same sensory inputs and the other assuming that the modules (e.g., glomeruli) have different receptive fields in odor space. We compare the implications of these models for the testing of mixed odors from a single source. PMID:8016093

  18. 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

  19. Segregated labeling of olfactory bulb projection neurons based on their birthdates.

    PubMed

    Imamura, Fumiaki; Greer, Charles A

    2015-01-01

    Mitral and tufted cells are the projection neurons of the olfactory bulb (OB). We previously reported that somata location and innervation patterns were different between early- and late-born mitral cells (Imamura et al., 2011). Here, we introduced a plasmid that drives the expression of a GFP gene into the mouse OB using in utero electroporation, and demonstrated that we can deliver the plasmid vectors into distinct subsets of OB projection neurons by changing the timing of electroporation after fertilisation. The electroporation performed at embryonic day (E)10 preferentially labeled mitral cells in the accessory OB and main OB mitral cells in dorsomedial mitral cell layer (MCL). In contrast, the E12 electroporation introduced the plasmid vectors preferentially into main OB mitral cells in the ventrolateral MCL and tufted cells. Combining these data with BrdU injections, we confirmed that E10 and E12 electroporation preferentially labeled early- and late-born projection neurons, respectively. This work introduces a novel method for segregated labeling of mouse olfactory bulb projection neurons based on their birthdates. With this technique we found that early- and late-born projection neurons extend their secondary dendrites in the deep and superficial external plexiform layer (EPL), respectively. Although a similar segregation has been suggested for mitral vs. tufted cell dendrites, we found mitral cells projecting secondary dendrites into the superficial EPL in E12-electroporated main OB. Our observations indicate that timing of neurogenesis regulates not only somata location and innervation patterns but also the laminar organisation of projection neuron dendrites in the EPL. PMID:25393912

  20. Segregated labeling of olfactory bulb projection neurons based on their birthdates

    PubMed Central

    Imamura, Fumiaki; Greer, Charles A.

    2014-01-01

    Mitral and tufted cells are the projection neurons of the olfactory bulb (OB). We previously reported that somata location and innervation patterns were different between early- and late-born mitral cells (Imamura et al., 2011). Here, we introduced a plasmid that drives the expression of a GFP gene into the mouse OB using in utero electroporation, and demonstrated that we can deliver the plasmid vectors into distinct subsets of OB projection neurons by changing the timing of electroporation after fertilization. The electroporation performed at embryonic day (E) 10 preferentially labeled mitral cells in the accessory OB and main OB mitral cells in dorsomedial mitral cell layer (MCL). In contrast, the E12 electroporation introduced the plasmid vectors preferentially into main OB mitral cells in the ventrolateral MCL and tufted cells. Combining these data with BrdU injections, we confirmed that E10 and E12 electroporation preferentially labeled early- and late-born projection neurons, respectively. This work introduces a novel method for segregated labeling of mouse olfactory bulb projection neurons based on their birthdates. With this technique we found that early- and late-born projection neurons extend their secondary dendrites in the deep and superficial external plexiform layer (EPL), respectively. Although a similar segregation has been suggested for mitral versus tufted cell dendrites, we found mitral cells projecting secondary dendrites into the superficial EPL in E12 electroporated main OB. Our observations indicate that timing of neurogenesis regulates not only somata location and innervation patterns, but also the laminar organization of projection neuron dendrites in the EPL. PMID:25393912

  1. Calcium-binding protein parvalbumin-immunoreactive neurons in the rat olfactory bulb. 2. Postnatal development.

    PubMed

    Kosaka, K; Heizmann, C W; Kosaka, T

    1994-01-01

    The laminar development of the external plexiform layer (EPL) in the rat main olfactory bulb and the postnatal development of parvalbumin-immunoreactive [PV(+)] neurons mainly located in this layer were studied in animals at postnatal week 1-4 at a light microscopic level. The EPL in the adult olfactory bulb consists of two sublayers, the inner sublayer (ISL) and the outer sublayer (OSL). The ISL was already developed well even at postnatal day 7 (P7), whereas the OSL was first recognized at P10 as a thin zone consisting of more or less loosely packed large-sized and small-to-medium-sized somata subjacent to the glomerular layer (GL). The OSL increased in thickness and came to occupy nearly one-third to -half of the EPL at P14. PV(+) neurons first appeared at P10 mainly in the inner border of EPL. Only a few PV(+) neurons were scattered in the EPL at P10, but they increased remarkably in number during P14-21. Some of these PV(+) neurons at P10 had an intensely immunoreactive soma, extending relatively long processes with varicosities and/or spines. At P14, PV(+) neurons were located not only in the ISL but also at the border between the ISL and OSL, but in the OSL proper they were rarely observed. These PV(+) neurons showed branched and complicated processes with numerous varicosities and spines, displaying more mature features than those in previous stages. Even at P14 many of these PV(+) neurons appeared to exhibit some characteristic structural features of those in the adult stage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7925803

  2. 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. PMID:25536543

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

    PubMed

    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

  4. 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

  5. Reduced olfactory bulb and tract volume in early Alzheimer's disease--a MRI study.

    PubMed

    Thomann, Philipp A; Dos Santos, Vasco; Toro, Pablo; Schönknecht, Peter; Essig, Marco; Schröder, Johannes

    2009-05-01

    Olfactory dysfunction has been reported to occur already in the early stages of Alzheimer's disease (AD) and to increase with disease severity. In neuropathological research, the deposition of neurofibrillary tangles and neuritic plaques in the olfactory bulb and tract (OBT) of AD patients has been consistently demonstrated. We used high-resolution magnetic resonance imaging (MRI) to determine the volume of the OBT in 21 patients with early AD and in 21 healthy comparison subjects. The OBT was manually traced on consecutive coronal slices. When compared to healthy controls, right, left and mean OBT volumes were significantly reduced in patients with AD (p<0.01). In AD patients, the mean OBT volume was significantly correlated with global cognitive performance as determined by the mini-mental state examination (r=0.605; p=0.004). Manual tracing on MRI images revealed OBT atrophy to be present early in the course of AD. Since the respective findings were associated with cognitive impairment, they may contribute to early recognition and diagnosis of the disease. PMID:17875348

  6. Effects of Functional Group Position on Spatial Representations of Aliphatic Odorants in the Rat Olfactory Bulb

    PubMed Central

    Johnson, Brett A.; Farahbod, Haleh; Saber, Sepideh; Leon, Michael

    2008-01-01

    Principles of olfactory coding can be clarified by studying the olfactory bulb activity patterns that are evoked by odorants differing systematically in chemical structure. In the present study, we used series of aliphatic esters, ketones, and alcohols (27 odorants total) to determine the effects of functional group position on glomerular-layer activity patterns. These patterns were measured as uptake of [14C]2-deoxyglucose and were mapped into standardized data matrices for statistical comparison across different rats. The magnitude of the effect of position differed greatly for the different functional groups. For ketones, there was little or no effect of position on evoked patterns. For esters, uptake in individual glomerular modules increased, while uptake in others decreased with changing group position, and yet the overall patterns remained similar. For alcohols, group position had a profound effect on evoked activity patterns. For example, moving the hydroxyl group in either heptanol or nonanol from the first to the fourth carbon changed the activity patterns so greatly that the major areas of response did not overlap. Within every functional group series, however, responses were globally chemotopic, such that pairs of odorants with the smallest difference in functional group position evoked the most similar patterns. These results help to define further the specificities of glomeruli within previously described glomerular modules, and they show that functional group position can be an important feature in encoding an odorant molecule. PMID:15678475

  7. Dynamics of olfactory bulb input and output activity during odor stimulation in zebrafish.

    PubMed

    Friedrich, Rainer W; Laurent, Gilles

    2004-06-01

    The processing of odor-evoked activity in the olfactory bulb (OB) of zebrafish was studied by extracellular single unit recordings from the input and output neurons, i.e., olfactory receptor neurons (ORNs) and mitral cells (MCs), respectively. A panel of 16 natural amino acid odors was used as stimuli. Responses of MCs, but not ORNs, changed profoundly during the first few hundred milliseconds after response onset. In MCs, but not ORNs, the total evoked excitatory activity in the population was initially odor-dependent but subsequently converged to a common level. Hence, the overall population activity is regulated by network interactions in the OB. The tuning widths of both ORN and MC response profiles were similar and, on average, stable over time. However, when analyzed for individual neurons, MC response profiles could sharpen (excitatory response to fewer odors) or broaden (excitatory response to more odors), whereas ORN response profiles remained nearly unchanged. Several observations indicate that dynamic inhibition plays an important role in this remodeling. Finally, the reliability of odor identification based on MC population activity patterns improved over time, whereas odor identification based on ORN activity patterns was most reliable early in the odor response. These results demonstrate that several properties of MC, but not ORN, activity change during the initial phase of the odor response with important consequences for odor-encoding activity patterns. Furthermore, our data indicate that inhibitory interactions in the OB are important in dynamically shaping the activity of OB output neurons. PMID:14960561

  8. Functional organization of glomerular maps in the mouse accessory olfactory bulb

    PubMed Central

    Hammen, Gary F.; Turaga, Diwakar; Holy, Timothy E.; Meeks, Julian P.

    2014-01-01

    Summary The mammalian accessory olfactory system (AOS) extracts information about species, sex, and individual identity from social odors, but its functional organization remains unclear. We imaged presynaptic Ca2+ signals in vomeronasal inputs to the accessory olfactory bulb (AOB) during peripheral stimulation using light sheet microscopy. Urine- and steroid-responsive glomeruli densely innervated the anterior AOB. Glomerular activity maps for sexually mature female mouse urine overlapped maps for juvenile and/or gonadectomized urine of both sexes, whereas maps for sexually mature male urine were highly distinct. Further spatial analysis revealed a complicated organization involving selective juxtaposition and dispersal of functionally-grouped glomerular classes. Glomeruli that were similarly tuned to urines were often closely associated, whereas more disparately tuned glomeruli were selectively dispersed. Maps to a panel of sulfated steroid odorants identified tightly-juxtaposed groups that were disparately tuned and dispersed groups that were similarly tuned. These results reveal a modular, non-chemotopic spatial organization in the AOB. PMID:24880215

  9. 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. PMID:25140258

  10. The Interplay between Reproductive Social Stimuli and Adult Olfactory Bulb Neurogenesis

    PubMed Central

    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. PMID:25140258

  11. Odorant recognition using biological responses recorded in olfactory bulb of rats.

    PubMed

    Vizcay, Marcela A; Duarte-Mermoud, Manuel A; Aylwin, María de la Luz

    2015-01-01

    In this study we applied pattern recognition (PR) techniques to extract odorant information from local field potential (LFP) signals recorded in the olfactory bulb (OB) of rats subjected to different odorant stimuli. We claim that LFP signals registered on the OB, the first stage of olfactory processing, are stimulus specific in animals with normal sensory experience, and that these patterns correspond to the neural substrate likely required for perceptual discrimination. Thus, these signals can be used as input to an artificial odorant classification system with great success. In this paper we have designed and compared the performance of several configurations of artificial olfaction systems (AOS) based on the combination of four feature extraction (FE) methods (Principal Component Analysis (PCA), Fisher Transformation (FT), Sammon NonLinear Map (NLM) and Wavelet Transform (WT)), and three PR techniques (Linear Discriminant Analysis (LDA), Multilayer Perceptron (MLP) and Support Vector Machine (SVM)), when four different stimuli are presented to rats. The best results were reached when PCA extraction followed by SVM as classifier were used, obtaining a classification accuracy of over 95% for all four stimuli. PMID:25464359

  12. Activity regulates functional connectivity from the vomeronasal organ to the accessory olfactory bulb.

    PubMed

    Hovis, Kenneth R; Ramnath, Rohit; Dahlen, Jeffrey E; Romanova, Anna L; LaRocca, Greg; Bier, Mark E; Urban, Nathaniel N

    2012-06-01

    The mammalian accessory olfactory system is specialized for the detection of chemicals that identify kin and conspecifics. Vomeronasal sensory neurons (VSNs) residing in the vomeronasal organ project axons to the accessory olfactory bulb (AOB), where they form synapses with principal neurons known as mitral cells. The organization of this projection is quite precise and is believed to be essential for appropriate function of this system. However, how this precise connectivity is established is unknown. We show here that in mice the vomeronasal duct is open at birth, allowing external chemical stimuli access to sensory neurons, and that these sensory neurons are capable of releasing neurotransmitter to downstream neurons as early as the first postnatal day (P). Using major histocompatibility complex class I peptides to activate a selective subset of VSNs during the first few postnatal days of development, we show that increased activity results in exuberant VSN axonal projections and a delay in axonal coalescence into well defined glomeruli in the AOB. Finally, we show that mitral cell dendritic refinement occurs just after the coalescence of presynaptic axons. Such a mechanism may allow the formation of precise connectivity with specific glomeruli that receive input from sensory neurons expressing the same receptor type. PMID:22674266

  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. Retronasal odor concentration coding in glomeruli of the rat olfactory bulb

    PubMed Central

    Gautam, Shree Hari; Short, Shaina M.; Verhagen, Justus V.

    2014-01-01

    The mammalian olfactory system processes odorants presented orthonasally (inhalation through the nose) and also retronasally (exhalation), enabling identification of both external as well as internal objects during food consumption. There are distinct differences between ortho- and retronasal air flow patterns, psychophysics, multimodal integration, and glomerular responses. Recent work indicates that rats can also detect odors retronasally, that rats can associate retronasal odors with tastes, and that their olfactory bulbs (OBs) can respond to retronasal odorants but differently than to orthonasal odors. To further characterize retronasal OB input activity patterns, experiments here focus on determining the effects of odor concentration on glomerular activity by monitoring calcium activity in the dorsal OB of rats using a dextran-conjugated calcium-sensitive dye in vivo. Results showed reliable concentration-response curves that differed between odorants, and recruitment of additional glomeruli, as odor concentration increased. We found evidence of different concentration-response functions between glomeruli, that in turn depended on odor. Further, the relation between dynamics and concentration differed remarkably among retronasal odorants. These dynamics are suggested to reduce the odor map ambiguity based on response amplitude. Elucidating the coding of retronasal odor intensity is fundamental to the understanding of feeding behavior and the neural basis of flavor. These data further establish and refine the rodent model of flavor neuroscience. PMID:25386123

  15. 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

  16. 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

  17. 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

  18. Olfactory Enrichment Influences Adult Neurogenesis Modulating GAD67 and Plasticity-Related Molecules Expression in Newborn Cells of the Olfactory Bulb

    PubMed Central

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

    2009-01-01

    The olfactory bulb (OB) is a highly plastic region of the adult mammalian brain characterized by continuous integration of inhibitory interneurons of the granule (GC) and periglomerular cell (PGC) types. Adult-generated OB interneurons are selected to survive in an experience-dependent way but the mechanisms that mediate the effects of experience on OB neurogenesis are unknown. Here we focus on the new-generated PGC population which is composed by multiple subtypes. Using paradigms of olfactory enrichment and/or deprivation combined to BrdU injections and quantitative confocal immunohistochemical analyses, we studied the effects of olfactory experience on adult-generated PGCs at different survival time and compared PGC to GC modulation. We show that olfactory enrichment similarly influences PGCs and GCs, increasing survival of newborn cells and transiently modulating GAD67 and plasticity-related molecules expression. However, PGC maturation appears to be delayed compared to GCs, reflecting a different temporal dynamic of adult generated olfactory interneuron integration. Moreover, olfactory enrichment or deprivation do not selectively modulate the survival of specific PGC phenotypes, supporting the idea that the integration rate of distinct PGC subtypes is independent from olfactory experience. PMID:19626121

  19. Mapping of odor-related neuronal activity in the olfactory bulb by high-resolution 2-deoxyglucose autoradiography

    SciTech Connect

    Lancet, D.; Greer, C.A.; Kauer, J.S.; Shepherd, G.M.

    1982-01-01

    The spatial distribution of odor-induced neuronal activity in the olfactory bulb, the first relay station of the olfactory pathway, is believed to reflect important aspects of chemosensory coding. We report here the application of high-resolution 2-deoxyglucose autoradiography to the mapping of spatial patterns of metabolic activity at the level of single neurons in the olfactory bulb. It was found that glomeruli, which are synaptic complexes containing the first synaptic relay, tend to be uniformly active or inactive during odor exposure. Differential 2-deoxyglucose uptake was also observed in the somata of projection neurons (mitral cells) and interneurons (periglomerular and granule cells). This confirms and extends our previous studies in which odor-specific laminar and focal uptake patterns were revealed by the conventional x-ray film 2-deoxyglucose method due to Sokoloff and colleagues (Sokoloff, L., Reivich, M., Kennedy, C., DesRosiers, M. H., Patlak, C. S., Pettigrew, K. D., Sakurada, O. and Shinohara, M. (1977) J. Neurochem. 28, 897-916). Based on results obtained by the two methods, it is suggested that the glomerulus as a whole serves as a functional unit of activity. The high-resolution results are interpreted in terms of the well-characterized synaptic organization of the olfactory bulb and also serve to illustrate the capability of the 2-deoxyglucose autoradiographic technique to map metabolic activity in single neurons of the vertebrate central nervous system.

  20. 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

  1. Sequential arrival and graded secretion of Sema3F by olfactory neuron axons specify map topography at the bulb.

    PubMed

    Takeuchi, Haruki; Inokuchi, Kasumi; Aoki, Mari; Suto, Fumikazu; Tsuboi, Akio; Matsuda, Ikuo; Suzuki, Misao; Aiba, Atsu; Serizawa, Shou; Yoshihara, Yoshihiro; Fujisawa, Hajime; Sakano, Hitoshi

    2010-06-11

    In the mouse olfactory system, the anatomical locations of olfactory sensory neurons (OSNs) roughly correlate with their axonal projection sites along the dorsal-ventral (D-V) axis of the olfactory bulb (OB). Here we report that an axon guidance receptor, Neuropilin-2 (Nrp2), and its repulsive ligand, Semaphorin-3F (Sema3F), are expressed by OSNs in a complementary manner that is important for establishing olfactory map topography. Sema3F is secreted by early-arriving axons of OSNs and is deposited at the anterodorsal OB to repel Nrp2-positive axons that arrive later. Sequential arrival of OSN axons as well as the graded and complementary expression of Nrp2 and Sema3F by OSNs help to form the topographic order along the D-V axis. PMID:20550939

  2. Increased Olfactory Bulb BDNF Expression Does Not Rescue Deficits in Olfactory Neurogenesis in the Huntington's Disease R6/2 Mouse.

    PubMed

    Smail, Shamayra; Bahga, Dalbir; McDole, Brittnee; Guthrie, Kathleen

    2016-03-01

    Huntington's disease (HD) is an inherited neurodegenerative disorder caused by expansion of CAG trinucleotide repeats in the huntingtin gene. Mutant huntingtin protein (mhtt) interferes with the actions of brain-derived neurotrophic factor (BDNF), and BDNF signaling is reduced in the diseased striatum. Loss of this trophic support is thought to contribute to loss of striatal medium spiny neurons in HD. Increasing BDNF in the adult striatum or ventricular ependyma slows disease progression in HD mouse models, and diverts subventricular zone (SVZ)-derived neuroblasts from their normal destination, the olfactory bulb, to the striatum, where some survive and develop features of mature neurons. Most neuroblasts that migrate to the olfactory bulb differentiate as granule cells, with approximately half surviving whereas others undergo apoptosis. In the R6/2 HD mouse model, survival of adult-born granule cells is reduced. Newly maturing cells express the BDNF receptor TrkB, suggesting that mhtt may interfere with normal BDNF trophic activity, increasing their loss. To determine if augmenting BDNF counteracts this, we examined granule cell survival in R6/2 mice that overexpress BDNF in olfactory bulb. Although we detected a decline in apoptosis, increased BDNF was not sufficient to normalize granule cell survival within their normal target in R6/2 mice. PMID:26783111

  3. 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. PMID:23774163

  4. Estradiol-induced neurogenesis in the female accessory olfactory bulb is required for the learning of the male odor.

    PubMed

    Brus, Maïna; Trouillet, Anne-Charlotte; Hellier, Vincent; Bakker, Julie

    2016-08-01

    Odors processed by the main and accessory olfactory bulbs (MOB, AOB) are important for sexual behavior. Interestingly, both structures continue to receive new neurons during adulthood. A role for olfactory neurogenesis in sexual behavior in female mice has recently been shown and gonadal hormones such as estradiol can modulate adult neurogenesis. Therefore, we wanted to determine the role of estradiol in learning the odors of sexual partners and in the adult neurogenesis of female aromatase knockout mice (ArKO), unable to produce estradiol. Female wild-type (WT) and ArKO mice were exposed to male odors during 7 days, and olfactory preferences, cell proliferation, cell survival and functional involvement of newborn neurons were analyzed, using BrdU injections, in combination with a marker of cell activation (Zif268) and neuronal fate (doublecortin, NeuN). Behavioral tasks indicated that both WT and ArKO females were able to discriminate between the odors of two different males, but ArKO mice failed to learn the familiar male odor. Proliferation of newborn cells was reduced in ArKO mice only in the dentate gyrus of the hippocampus. Olfactory exposure decreased cell survival in the AOB in WT females, suggesting a role for estradiol in a structure involved in sexual behavior. Finally, newborn neurons do not seem to be functionally involved in the AOB of ArKO mice compared with WT, when females were exposed to the odor of a familiar male, suggesting that estradiol-induced neurogenesis in the AOB is required for the learning of the male odor in female mice. Aromatase knockout mice (ArKO) presented deficits in olfactory preferences without affecting their olfactory discrimination abilities, and showed no functional involvement of newborn neurons in the accessory olfactory bulb (AOB) in response to the odor of a familiar male. These results suggest that estradiol-induced neurogenesis in the female AOB is required for the learning of the male odor. PMID:27216894

  5. Sexual activity increases the number of newborn cells in the accessory olfactory bulb of male rats

    PubMed Central

    Portillo, Wendy; Unda, Nancy; Camacho, Francisco J.; Sánchez, María; Corona, Rebeca; Arzate, Dulce Ma.; Díaz, Néstor F.; Paredes, Raúl G.

    2012-01-01

    In rodents, sexual behavior depends on the adequate detection of sexually relevant stimuli. The olfactory bulb (OB) is a region of the adult mammalian brain undergoing constant cell renewal by continuous integration of new granular and periglomerular neurons in the accessory (AOB) and main (MOB) olfactory bulbs. The proliferation, migration, survival, maturation, and integration of these new cells to the OB depend on the stimulus that the subjects received. We have previously shown that 15 days after females control (paced) the sexual interaction an increase in the number of cells is observed in the AOB. No changes are observed in the number of cells when females are not allowed to control the sexual interaction. In the present study we investigated if in male rats sexual behavior increases the number of new cells in the OB. Male rats were divided in five groups: (1) males that did not receive any sexual stimulation, (2) males that were exposed to female odors, (3) males that mated for 1 h and could not pace their sexual interaction, (4) males that paced their sexual interaction and ejaculated one time and (5) males that paced their sexual interaction and ejaculated three times. All males received three injections of the DNA synthesis marker bromodeoxyuridine at 1h intervals, starting 1 h before the beginning of the behavioral test. Fifteen days later, males were sacrificed and the brains were processed to identify new cells and to evaluate if they differentiated into neurons. The number of newborn cells increased in the granular cell layer (GrCL; also known as the internal cell layer) of the AOB in males that ejaculated one or three times controlling (paced) the rate of the sexual interaction. Some of these new cells were identified as neurons. In contrast, no significant differences were found in the mitral cell layer (also known as the external cell layer) and glomerular cell layer (GlCL) of the AOB. In addition, no significant differences were found between

  6. Sex pheromones and amino acids evoke distinctly different spatial patterns of electrical activity in the goldfish olfactory bulb.

    PubMed

    Hanson, L R; Sorensen, P W; Cohen, Y

    1998-11-30

    Until now, electrophysiological studies of the vertebrate olfactory bulb have tested only 'generalist' cues. These studies suggest that odorants are discriminated by a broadly distributed spatial map. In this study, we tested for the first time in a vertebrate the hypothesis that 'specialist' cues (pheromones) are discriminated by a more restricted component of the olfactory bulb. Our model is the male goldfish, Carassius auratus, for which five sex pheromones with both behavioral and physiological activity have now been identified. Electrical activity (electroencephalography: EEG) was recorded over a 12-point grid from the surface of the olfactory bulb, while fish were exposed to one of ten stimuli including: five sex pheromones, two amino acids, two bile steroids and a control. Evoked activity was evaluated by time series analysis. Power ratios were calculated by dividing the power of the dominant frequency in the power spectrum before stimulation by the power of the dominant frequency during stimulation. Next, the average magnitudes of odorant responses were compared using analysis of variance (ANOVA). The spatial patterning of these responses was also described using cluster analysis, which grouped odorants based on the similarity of their spatial patterns of activity. Although all odorants elicited EEG responses with similar dominant frequencies, odorant-specific differences were evident in the size and distribution of these responses. Sex pheromones and bile steroids elicited relatively small responses that were spatially restricted in distinctive manners, although some overlap was evident. In contrast, amino acids consistently produced large responses at all positions. These results are consistent with the hypothesis that vertebrate pheromones are discriminated by a distinctive subcomponent of the vertebrate olfactory system comprised of a relatively small number of olfactory neurons. PMID:10049233

  7. 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. PMID:25216299

  8. COUP-TFI controls activity-dependent tyrosine hydroxylase expression in adult dopaminergic olfactory bulb interneurons.

    PubMed

    Bovetti, Serena; Bonzano, Sara; Garzotto, Donatella; Giannelli, Serena Gea; Iannielli, Angelo; Armentano, Maria; Studer, Michèle; De Marchis, Silvia

    2013-12-01

    COUP-TFI is an orphan nuclear receptor acting as a strong transcriptional regulator in different aspects of forebrain embryonic development. In this study, we investigated COUP-TFI expression and function in the mouse olfactory bulb (OB), a highly plastic telencephalic region in which continuous integration of newly generated inhibitory interneurons occurs throughout life. OB interneurons belong to different populations that originate from distinct progenitor lineages. Here, we show that COUP-TFI is highly expressed in tyrosine hydroxylase (TH)-positive dopaminergic interneurons in the adult OB glomerular layer (GL). We found that odour deprivation, which is known to downregulate TH expression in the OB, also downregulates COUP-TFI in dopaminergic cells, indicating a possible correlation between TH- and COUP-TFI-activity-dependent action. Moreover, we demonstrate that conditional inactivation of COUP-TFI in the EMX1 lineage results in a significant reduction of both TH and ZIF268 expression in the GL. Finally, lentiviral vector-mediated COUP-TFI deletion in adult-generated interneurons confirmed that COUP-TFI acts cell-autonomously in the control of TH and ZIF268 expression. These data indicate that COUP-TFI regulates TH expression in OB cells through an activity-dependent mechanism involving ZIF268 induction and strongly argue for a maintenance rather than establishment function of COUP-TFI in dopaminergic commitment. Our study reveals a previously unknown role for COUP-TFI in the adult brain as a key regulator in the control of sensory-dependent plasticity in olfactory dopaminergic neurons. PMID:24227652

  9. Impaired olfactory bulb neurogenesis depends on the presence of human wild-type alpha-synuclein.

    PubMed

    May, V E L; Nuber, S; Marxreiter, F; Riess, O; Winner, B; Winkler, J

    2012-10-11

    Synucleinopathies including Parkinson's disease (PD) are characterized by the accumulation of alpha-synuclein (α-syn) within neural cell bodies and their processes. Transgenic mice overexpressing human wild-type or mutant forms of α-syn under the control of different promoters were developed to analyse the underlying neuropathology of PD. One of the earliest clinical symptoms associated with PD is olfactory impairment. The generation of new neurons persists up to adulthood in mammals, in particular the olfactory bulb (OB). In order to assess this process in relation to α-syn accumulation, we used mice overexpressing human wild-type α-syn under the regulatable control (tet-off) of the calcium/calmodulin-dependent protein kinase IIα-promoter (CaMKII). We observed a decrease in OB neurogenesis in transgenic animals compared to controls using 5-bromo-2'-deoxyuridine (BrdU) to label newly generated cells (neuron-specific nuclear protein; NeuN). After cessation of transgene expression we detected an increase in newly generated cells both in granular (GCL) and glomerular (GLOM) layers of the OB. This led to a rescue of newly generated neurons (BrdU(+)/NeuN(+)) within the GLOM with a distinct specificity for the dopaminergic subpopulation. In contrast, we did not detect a cell-specific rescue of neuronal cells in the GCL suggesting diverse effects of alpha-synucleinopathy in both interneuronal layers of the OB. Colabelling of BrdU with glial markers showed that a differentiation into neither astroglia nor microglia attributed to the observed phenotype in the GCL. In particular, BrdU(+) particles located within microglial cells were predominantly associated close to the membrane therefore the resembling phagocytosed nuclear fragments of BrdU(+) cells. Thus, our study further contributes insights into α-syn accumulation as a causative player in the impairment of adult neurogenesis and emphasizes its diverse role in cell renewal of distinct OB cell layers. PMID:22814000

  10. 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

  11. 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

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

    PubMed

    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

  13. 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

  14. 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

  15. Adult neurogenesis and specific replacement of interneuron subtypes in the mouse main olfactory bulb

    PubMed Central

    Bagley, Joshua; LaRocca, Greg; Jimenez, Daniel A; Urban, Nathaniel N

    2007-01-01

    Background New neurons are generated in the adult brain from stem cells found in the subventricular zone (SVZ). These cells proliferate in the SVZ, generating neuroblasts which then migrate to the main olfactory bulb (MOB), ending their migration in the glomerular layer (GLL) and the granule cell layer (GCL) of the MOB. Neuronal populations in these layers undergo turnover throughout life, but whether all neuronal subtypes found in these areas are replaced and when neurons begin to express subtype-specific markers is not known. Results Here we use BrdU injections and immunohistochemistry against (calretinin, calbindin, N-copein, tyrosine hydroxylase and GABA) and show that adult-generated neurons express markers of all major subtypes of neurons in the GLL and GCL. Moreover, the fractions of new neurons that express subtype-specific markers at 40 and 75 days post BrdU injection are very similar to the fractions of all neurons expressing these markers. We also show that many neurons in the glomerular layer do not express NeuN, but are readily and specifically labeled by the fluorescent nissl stain Neurotrace. Conclusion The expression of neuronal subtype-specific markers by new neurons in the GLL and GCL changes rapidly during the period from 14–40 days after BrdU injection before reaching adult levels. This period may represent a critical window for cell fate specification similar to that observed for neuronal survival. PMID:17996088

  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. PMID:26674618

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. Parvalbumin immunoreactive neurons in the main olfactory bulb of the house musk shrew, Suncus murinus.

    PubMed

    Kakuta, S; Oda, S; Takayanagi, M; Kishi, K

    1998-01-01

    The distribution, morphological features, and postnatal development of parvalbumin (PV) immunoreactive neurons in the main olfactory bulb (MOB) of the house musk shrew, Suncus murinus, were studied to report for the first time on PV positive bulbar interneurons in the order Insectivora. In adult animals, PV neurons are distributed in the glomerular layer (GL), the external plexiform layer (EPL), the internal plexiform layer (IPL) and the granule cell layer (GCL) of the MOB. These neurons were identified as a subpopulation of periglomerular cells and perinidal cells [Alonso et al., 1995] in the GL and at the GL-EPL border, respectively, and as bipolar and multipolar neurons in the EPL and four types of the interneurons (horizontal cells, Cajal cells, Golgi cells, and bitufted cells) in the layers deeper than the mitral cell layer. During development of PV neurons, neurons exhibiting extremely faint PV immunoreactivity first appeared in the GCL at postnatal day 14 and increased markedly in number and intensity of their PV immunoreactivity from postnatal days 14 to 28. At postnatal day 21, PV neurons were identified as periglomerular cells in the GL, perinidal cells at the GL-EPL border, and morphologically unidentifiable neurons in the EPL, IPL and GCL. At postnatal day 28, PV neurons exhibited a nearly adult pattern with respect to distribution and structural features. The present results strongly suggest that a wide variety of PV positive neurons in the MOB of the house musk shrew may develop postnatally. PMID:9807013

  4. 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

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

    PubMed

    Lim, Daniel A; Alvarez-Buylla, Arturo

    2016-01-01

    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. PMID:27048191

  6. Tonic inhibition sets the state of excitability in olfactory bulb granule cells

    PubMed Central

    Labarrera, Christina; London, Michael; Angelo, Kamilla

    2013-01-01

    GABAergic granule cells (GCs) regulate, via mitral cells, the final output from the olfactory bulb to piriform cortex and are central for the speed and accuracy of odour discrimination. However, little is known about the local circuits in which GCs are embedded and how GCs respond during functional network activity. We recorded inhibitory and excitatory currents evoked during a single sniff-like odour presentation in GCs in vivo. We found that synaptic excitation was extensively activated across cells, whereas phasic inhibition was rare. Furthermore, our analysis indicates that GCs are innervated by a persistent firing of deep short axon cells that mediated the inhibitory evoked responses. Blockade of GABAergic synaptic input onto GCs revealed a tonic inhibitory current mediated by furosemide-sensitive GABAA receptors. The average current associated with this tonic GABAergic conductance was 3-fold larger than that of phasic inhibitory postsynaptic currents. We show that the pharmacological blockage of tonic inhibition markedly increased the occurrence of supra-threshold responses during an odour-stimulated sniff. Our findings suggest that GCs mediate recurrent or lateral inhibition, depending on the ambient level of extracellular GABA. PMID:23318869

  7. 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

  8. 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

  9. 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

  10. 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

  11. Characterization of solubilized atrial natriuretic peptide receptors from rat olfactory bulb and A10 cultured smooth muscle cells

    SciTech Connect

    Gibson, T.R.; Zyskind, A.D.; Glembotski, C.C.

    1988-08-01

    Atrial natriuretic peptide (ANP) receptors from A10 cultured vascular smooth muscle cells (VSMC) and rat olfactory bulbs have been solubilized and then pharmacologically and biochemically compared. The dissociation constant for 125I-ANP(99-126) was 12.7 pM for the VSMC-derived receptor and 164 pM for the olfactory receptor. Competition binding between 125I-ANP(99-126) and several unlabeled ANP analogs with the soluble olfactory receptor, demonstrated a rank order potency of ANP(99-126) = ANP(103-126) much greater than ANP(103-123). However, the rank order potency of the soluble VSMC ANP receptor was ANP(99-126) = ANP(103-126) = ANP(103-123). Therefore, the olfactory ANP receptor appears to require the complete COOH-terminal sequence of ANP as compared with the VSMC ANP receptor. When the 2 soluble receptor preparations were applied to a GTP-agarose column, a portion of the olfactory ANP receptor was retained on the column and could be eluted with 5 mM GTP, while the VSMC ANP receptor did not adsorb to the column. Since the olfactory bulb ANP receptor has been shown to contain a binding component of 116 kDa, while the VSMC ANP receptor binding component is 66 kDa, these receptors appear to be similar to the 2 receptor classes described recently in which the 120 kDa receptor that binds GTP is postulated to be coupled to guanylate cyclase, while the 60 kDa receptor does not bind GTP, is not coupled to guanylate cyclase, and may possess a hormone clearance function. Taken together, these data indicate that cyclic GMP appears to be a second messenger for ANP in the brain.

  12. Imaging Odor-Evoked Activities in the Mouse Olfactory Bulb using Optical Reflectance and Autofluorescence Signals

    PubMed Central

    Chery, Romain; L'Heureux, Barbara; Bendahmane, Mounir; Renaud, Rémi; Martin, Claire; Pain, Frédéric; Gurden, Hirac

    2011-01-01

    In the brain, sensory stimulation activates distributed populations of neurons among functional modules which participate to the coding of the stimulus. Functional optical imaging techniques are advantageous to visualize the activation of these modules in sensory cortices with high spatial resolution. In this context, endogenous optical signals that arise from molecular mechanisms linked to neuroenergetics are valuable sources of contrast to record spatial maps of sensory stimuli over wide fields in the rodent brain. Here, we present two techniques based on changes of endogenous optical properties of the brain tissue during activation. First the intrinsic optical signals (IOS) are produced by a local alteration in red light reflectance due to: (i) absorption by changes in blood oxygenation level and blood volume (ii) photon scattering. The use of in vivo IOS to record spatial maps started in the mid 1980's with the observation of optical maps of whisker barrels in the rat and the orientation columns in the cat visual cortex1. IOS imaging of the surface of the rodent main olfactory bulb (OB) in response to odorants was later demonstrated by Larry Katz's group2. The second approach relies on flavoprotein autofluorescence signals (FAS) due to changes in the redox state of these mitochondrial metabolic intermediates. More precisely, the technique is based on the green fluorescence due to oxidized state of flavoproteins when the tissue is excited with blue light. Although such signals were probably among the first fluorescent molecules recorded for the study of brain activity by the pioneer studies of Britton Chances and colleagues3, it was not until recently that they have been used for mapping of brain activation in vivo. FAS imaging was first applied to the somatosensory cortex in rodents in response to hindpaw stimulation by Katsuei Shibuki's group4. The olfactory system is of central importance for the survival of the vast majority of living species because it

  13. Expression of G proteins in the olfactory receptor neurons of the newt Cynops pyrrhogaster: their unique projection into the olfactory bulbs.

    PubMed

    Nakada, Tomoaki; Hagino-Yamagishi, Kimiko; Nakanishi, Koki; Yokosuka, Makoto; Saito, Toru R; Toyoda, Fumiyo; Hasunuma, Itaru; Nakakura, Takashi; Kikuyama, Sakae

    2014-10-15

    We analyzed the expression of G protein α subunits and the axonal projection into the brain in the olfactory system of the semiaquatic newt Cynops pyrrhogaster by immunostaining with antibodies against Gαolf and Gαo , by in situ hybridization using probes for Gαolf , Gαo , and Gαi2 , and by neuronal tracing with DiI and DiA. The main olfactory epithelium (OE) consists of two parts, the ventral OE and dorsal OE. In the ventral OE, the Gαolf - and Gαo -expressing neurons are located in the apical and basal zone of the OE, respectively. This zonal expression was similar to that of the OE in the middle cavity of the fully aquatic toad Xenopus laevis. However, the Gαolf - and Gαo -expressing neurons in the newt ventral OE project their axons toward the main olfactory bulb (MOB) and the accessory olfactory bulb (AOB), respectively, whereas in Xenopus, the axons of both neurons project solely toward the MOB. In the dorsal OE of the newt, as in the principal cavity of Xenopus, the majority of the neurons express Gαolf and extend their axons into the MOB. In the vomeronasal organ (VNO), the neurons mostly express Gαo . These neurons and quite a few Gαolf -expressing neurons project their axons toward the AOB. This feature is similar to that in the terrestrial toad Bufo japonicus and is different from that in Xenopus, in which VNO neurons express solely Gαo , although their axons invariably project toward the AOB. We discuss the findings in the light of diversification and evolution of the vertebrate olfactory system. PMID:24771457

  14. 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

  15. Egr-1 antisense oligodeoxynucleotide administration into the olfactory bulb impairs olfactory learning in the greater short-nosed fruit bat Cynopterus sphinx.

    PubMed

    Ganesh, Ambigapathy; Bogdanowicz, Wieslaw; Balamurugan, Krishnaswamy; Ragu Varman, Durairaj; Rajan, Koilmani Emmanuvel

    2012-08-30

    Postsynaptic densities (PSDs) contain proteins that regulate synaptic transmission. We examined two important examples of these, calcium/calmodulin-dependent protein kinase II (CaMKII) and PSD-95, in regard to the functional role of early growth response gene-1 (egr-1) in regulation of olfactory learning in the greater short-nosed fruit bat Cynopterus sphinx (family Pteropodidae). To test whether activation of egr-1 in the olfactory bulb (OB) is required for olfactory memory of these bats, bilaterally canulated individuals were infused with antisense (AS) or non-sense (NS)-oligodeoxynucleotides (ODN) of egr-1, or with phosphate buffer saline (PBS), 2h before the olfactory training. Our results showed that behavioral training significantly up-regulates immediate early gene (IEG) EGR-1 and key synaptic proteins Synaptotagmin-1(SYT-1), CaMKII and PSD-95, and phosphorylation of CaMKII in the OB at the protein level per se. Subsequently, we observed that egr-1 antisense-ODN infusion in the OB impaired olfactory memory and down regulates the expression of CaMKII and PSD-95, and the phosphorylation of CaMKII but not SYT-1. In contrast, NS-ODN or PBS had no effect on the expression of the PSDs CaMKII or PSD-95, or on the phosphorylation of CaMKII. When the egr-1 NS-ODN was infused in the OB after training for the novel odor there was no effect on olfactory memory. These findings suggest that egr-1 control the activation of CaMKII and PSD-95 during the process of olfactory memory formation. PMID:22796292

  16. Selective imaging of presynaptic activity in the mouse olfactory bulb shows concentration and structure dependence of odor responses in identified glomeruli

    PubMed Central

    Fried, Hans U.; Fuss, Stefan H.; Korsching, Sigrun I.

    2002-01-01

    More chemicals can be smelled than there are olfactory receptors for them, necessitating a combinatorial representation by somewhat broadly tuned receptors. To understand the perception of odor quality and concentration, it is essential to establish the nature of the receptor repertoires that are activated by particular odorants at particular concentrations. We have taken advantage of the one-to-one correspondence of glomeruli and olfactory receptor molecules in the mouse olfactory bulb to analyze the tuning properties of a major receptor population by high resolution calcium imaging of odor responses selectively in the presynaptic compartment of glomeruli. We show that eighty different olfactory receptors projecting to the dorsal olfactory bulb respond to high concentrations of aldehydes with limited specificity. Varying ensembles of about 10 to 20 receptors encode any particular aldehyde at low stimulus concentrations with high specificity. Even normalized odor response patterns are markedly concentration dependent, caused by pronounced differences in affinity within the aldehyde receptor repertoire. PMID:11854464

  17. 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. PMID:25622576

  18. Signaling between periglomerular cells reveals a bimodal role for GABA in modulating glomerular microcircuitry in the olfactory bulb

    PubMed Central

    Parsa, Pirooz Victor; D’Souza, Rinaldo David; Vijayaraghavan, Sukumar

    2015-01-01

    In the mouse olfactory bulb glomerulus, the GABAergic periglomerular (PG) cells provide a major inhibitory drive within the microcircuit. Here we examine GABAergic synapses between these interneurons. At these synapses, GABA is depolarizing and exerts a bimodal control on excitability. In quiescent cells, activation of GABAA receptors can induce the cells to fire, thereby providing a means for amplification of GABA release in the glomerular microcircuit via GABA-induced GABA release. In contrast, GABA is inhibitory in neurons that are induced to fire tonically. PG–PG interactions are modulated by nicotinic acetylcholine receptors (nAChRs), and our data suggest that changes in intracellular calcium concentrations triggered by nAChR activation can be amplified by GABA release. Our results suggest that bidirectional control of inhibition in PG neurons can allow for modulatory inputs, like the cholinergic inputs from the basal forebrain, to determine threshold set points for filtering out weak olfactory inputs in the glomerular layer of the olfactory bulb via the activation of nAChRs. PMID:26170298

  19. 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

  20. In Vivo Study of Dynamics and Stability of Dendritic Spines on Olfactory Bulb Interneurons in Xenopus laevis Tadpoles

    PubMed Central

    Huang, Yu-Bin; Hu, Chun-Rui; Zhang, Li; Yin, Wu; Hu, Bing

    2015-01-01

    Dendritic spines undergo continuous remodeling during development of the nervous system. Their stability is essential for maintaining a functional neuronal circuit. Spine dynamics and stability of cortical excitatory pyramidal neurons have been explored extensively in mammalian animal models. However, little is known about spiny interneurons in non-mammalian vertebrate models. In the present study, neuronal morphology was visualized by single-cell electroporation. Spiny neurons were surveyed in the Xenopus tadpole brain and observed to be widely distributed in the olfactory bulb and telencephalon. DsRed- or PSD95-GFP-expressing spiny interneurons in the olfactory bulb were selected for in vivo time-lapse imaging. Dendritic protrusions were classified as filopodia, thin, stubby, or mushroom spines based on morphology. Dendritic spines on the interneurons were highly dynamic, especially the filopodia and thin spines. The stubby and mushroom spines were relatively more stable, although their stability significantly decreased with longer observation intervals. The 4 spine types exhibited diverse preferences during morphological transitions from one spine type to others. Sensory deprivation induced by severing the olfactory nerve to block the input of mitral/tufted cells had no significant effects on interneuron spine stability. Hence, a new model was established in Xenopus laevis tadpoles to explore dendritic spine dynamics in vivo. PMID:26485435

  1. 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

  2. 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

  3. The Origin, Development and Molecular Diversity of Rodent Olfactory Bulb Glutamatergic Neurons Distinguished by Expression of Transcription Factor NeuroD1

    PubMed Central

    Roybon, Laurent; Mastracci, Teresa L.; Li, Joyce; Stott, Simon R. W.; Leiter, Andrew B.; Sussel, Lori; Brundin, Patrik; Li, Jia-Yi

    2015-01-01

    Production of olfactory bulb neurons occurs continuously in the rodent brain. Little is known, however, about cellular diversity in the glutamatergic neuron subpopulation. In the central nervous system, the basic helix-loop-helix transcription factor NeuroD1 (ND1) is commonly associated with glutamatergic neuron development. In this study, we utilized ND1 to identify the different subpopulations of olfactory bulb glutamategic neurons and their progenitors, both in the embryo and postnatally. Using knock-in mice, transgenic mice and retroviral transgene delivery, we demonstrate the existence of several different populations of glutamatergic olfactory bulb neurons, the progenitors of which are ND1+ and ND1- lineage-restricted, and are temporally and regionally separated. We show that the first olfactory bulb glutamatergic neurons produced – the mitral cells – can be divided into molecularly diverse subpopulations. Our findings illustrate the complexity of neuronal diversity in the olfactory bulb and that seemingly homogenous neuronal populations can consist of multiple subpopulations with unique molecular signatures of transcription factors and expressing neuronal subtype-specific markers. PMID:26030886

  4. 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

  5. PACAP modulation of calcium ion activity in developing granule cells of the neonatal mouse olfactory bulb

    PubMed Central

    Irwin, Mavis; Greig, Ann; Tvrdik, Petr

    2014-01-01

    Ca2+ activity in the CNS is critical for the establishment of developing neuronal circuitry prior to and during early sensory input. In developing olfactory bulb (OB), the neuromodulators that enhance network activity are largely unknown. Here we provide evidence that pituitary adenylate cyclase-activating peptide (PACAP)-specific PAC1 receptors (PAC1Rs) expressed in postnatal day (P)2–P5 mouse OB are functional and enhance network activity as measured by increases in calcium in genetically identified granule cells (GCs). We used confocal Ca2+ imaging of OB slices from Dlx2-tdTomato mice to visualize GABAergic GCs. To address whether the PACAP-induced Ca2+ oscillations were direct or indirect effects of PAC1R activation, we used antagonists for the GABA receptors (GABARs) and/or glutamate receptors (GluRs) in the presence and absence of PACAP. Combined block of GABARs and GluRs yielded a 66% decrease in the numbers of PACAP-responsive cells, suggesting that 34% of OB neurons are directly activated by PACAP. Similarly, immunocytochemistry using anti-PAC1 antibody showed that 34% of OB neurons express PAC1R. Blocking either GluRs or GABARs alone indirectly showed that PACAP stimulates release of both glutamate and GABA, which activate GCs. The appearance of PACAP-induced Ca2+ activity in immature GCs suggests a role for PACAP in GC maturation. To conclude, we find that PACAP has both direct and indirect effects on neonatal OB GABAergic cells and may enhance network activity by promoting glutamate and GABA release. Furthermore, the numbers of PACAP-responsive GCs significantly increased between P2 and P5, suggesting that PACAP-induced Ca2+ activity contributes to neonatal OB development. PMID:25475351

  6. Protein kinase Calpha mediates a novel form of plasticity in the accessory olfactory bulb.

    PubMed

    Dong, C; Godwin, D W; Brennan, P A; Hegde, A N

    2009-10-20

    Modification of synapses in the accessory olfactory bulb (AOB) is believed to underlie pheromonal memory that enables mate recognition in mice. The memory, which is acquired with single-trial learning, forms only with coincident noradrenergic and glutamatergic inputs to the AOB. The mechanisms by which glutamate and norepinephrine (NE) alter the AOB synapses are not well understood. Here we present results that not only reconcile the earlier, seemingly contradictory, observations on the role of glutamate and NE in changing the AOB synapses, but also reveal novel mechanisms of plasticity. Our studies suggest that initially, glutamate acting at Group II metabotropic receptors and NE acting at alpha(2)-adrenergic receptors inhibit N-type and R-type Ca(2+) channels in mitral cells via a G-protein. The N-type and R-type Ca(2+) channel inhibition is reversed by activation of alpha(1)-adrenergic receptors and protein kinase Calpha (PKCalpha). Based on these results, we propose a hypothetical model for a new kind of synaptic plasticity in the AOB that accounts for the previous behavioral data on pheromonal memory. According to this model, initial inhibition of the Ca(2+) channels suppresses the GABAergic inhibitory feedback to mitral cells, causing disinhibition and Ca(2+) influx. NE also activates phospholipase C (PLC) through alpha(1)-adrenergic receptors generating inositol 1,4,5-trisphosphate and diacylglycerol (DAG). Calcium and DAG together activate PKCalpha which switches the disinhibition to increased inhibition of mitral cells. Thus, PKCalpha is likely to be a coincidence detector integrating glutamate and NE input in the AOB and bridging the short-term signaling to long-term structural changes resulting in enhanced inhibition of mitral cells that is thought to underlie memory formation. PMID:19580852

  7. 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

  8. Optimization of wavelengths sets for multispectral reflectance imaging of rat olfactory bulb activation in vivo

    NASA Astrophysics Data System (ADS)

    Renaud, Rémi; Bendahmane, Mounir; Chery, Romain; Martin, Claire; Gurden, Hirac; Pain, Frederic

    2012-06-01

    Wide field multispectral imaging of light backscattered by brain tissues provides maps of hemodynamics changes (total blood volume and oxygenation) following activation. This technique relies on the fit of the reflectance images obtain at two or more wavelengths using a modified Beer-Lambert law1,2. It has been successfully applied to study the activation of several sensory cortices in the anesthetized rodent using visible light1-5. We have carried out recently the first multispectral imaging in the olfactory bulb6 (OB) of anesthetized rats. However, the optimization of wavelengths choice has not been discussed in terms of cross talk and uniqueness of the estimated parameters (blood volume and saturation maps) although this point was shown to be crucial for similar studies in Diffuse Optical Imaging in humans7-10. We have studied theoretically and experimentally the optimal sets of wavelength for multispectral imaging of rodent brain activation in the visible. Sets of optimal wavelengths have been identified and validated in vivo for multispectral imaging of the OB of rats following odor stimulus. We studied the influence of the wavelengths sets on the magnitude and time courses of the oxy- and deoxyhemoglobin concentration variations as well as on the spatial extent of activated brain areas following stimulation. Beyond the estimation of hemodynamic parameters from multispectral reflectance data, we observed repeatedly and for all wavelengths a decrease of light reflectance. For wavelengths longer than 590 nm, these observations differ from those observed in the somatosensory and barrel cortex and question the basis of the reflectance changes during activation in the OB. To solve this issue, Monte Carlo simulations (MCS) have been carried out to assess the relative contribution of absorption, scattering and anisotropy changes to the intrinsic optical imaging signals in somatosensory cortex (SsC) and OB model.

  9. 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

  10. 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