The Experts below are selected from a list of 4467 Experts worldwide ranked by ideXlab platform

Nathaniel N. Urban - One of the best experts on this subject based on the ideXlab platform.

  • timescale dependent shaping of correlation by olfactory bulb lateral inhibition
    Proceedings of the National Academy of Sciences of the United States of America, 2011
    Co-Authors: Sonya Giridhar, Brent Doiron, Nathaniel N. Urban
    Abstract:

    Neurons respond to sensory stimuli by altering the rate and temporal pattern of action potentials. These spike trains both encode and propagate information that guides behavior. Local inhibitory networks can affect the information encoded and propagated by neurons by altering correlations between different spike trains. Correlations introduce redundancy that can reduce encoding but also facilitate propagation of activity to downstream targets. Given this trade-off, how can networks maximize both encoding and propagation efficacy? Here, we examine this problem by measuring the effects of olfactory bulb inhibition on the pairwise statistics of Mitral Cell spiking. We evoked spiking activity in the olfactory bulb in vitro and measured how lateral inhibition shapes correlations across timescales. We show that inhibitory circuits simultaneously increase fast correlation (i.e., synchrony increases) and decrease slow correlation (i.e., firing rates become less similar). Further, we use computational models to show the benefits of fast correlation/slow decorrelation in the context of odor coding. Olfactory bulb inhibition enhances population-level discrimination of similar inputs, while improving propagation of Mitral Cell activity to cortex. Our findings represent a targeted strategy by which a network can optimize the correlation structure of its output in a dynamic, activity-dependent manner. This trade-off is not specific to the olfactory system, but rather our work highlights mechanisms by which neurons can simultaneously accomplish multiple, and sometimes competing, aspects of sensory processing.

  • Computing with Dendrodendritic Synapses in the Olfactory Bulb
    Annals of the New York Academy of Sciences, 2009
    Co-Authors: Nathaniel N. Urban, Armen C. Arevian
    Abstract:

    Decades of work in vivo and in vitro have provided a wealth of data on the properties of the reciprocal dendrodendritic synapses that connect olfactory bulb Mitral and granule Cells. However, hypotheses about the function of these connections have changed relatively little. These synapses are believed to mediate recurrent and lateral inhibition and thus, by analogy with lateral inhibition in other systems, have been proposed to play a role in sharpening Mitral Cell receptive fields and in generating oscillatory spiking in Mitral Cells. This description is likely to be partially accurate, but is likely to be a rather simplified and incomplete account of the function of these connections. In particular, current hypotheses about the function of dendrodendritic circuits do not account for some of the unusual features of reciprocal synapses that may allow olfactory bulb circuits to perform special functions. Here we review recent work on the physiology and function of olfactory bulb circuits and try to link the physiological properties of reciprocal synapses particular computations that the olfactory bulb may perform.

  • Activity-dependent gating of lateral inhibition in the mouse olfactory bulb
    Nature neuroscience, 2007
    Co-Authors: Armen C. Arevian, Vikrant Kapoor, Nathaniel N. Urban
    Abstract:

    Lateral inhibition is a circuit motif found throughout the nervous system that often generates contrast enhancement and center-surround receptive fields. We investigated the functional properties of the circuits mediating lateral inhibition between olfactory bulb principal neurons (Mitral Cells) in vitro. We found that the lateral inhibition received by Mitral Cells is gated by postsynaptic firing, such that a minimum threshold of postsynaptic activity is required before effective lateral inhibition is recruited. This dynamic regulation allows the strength of lateral inhibition to be enhanced between Cells with correlated activity. Simulations show that this regulation of lateral inhibition causes decorrelation of Mitral Cell activity that is evoked by similar stimuli, even when stimuli have no clear spatial structure. These results show that this previously unknown mechanism for specifying lateral inhibitory connections allows functional inhibitory connectivity to be dynamically remapped to relevant populations of neurons.

  • stimulus specific activity patterns in the granule Cell networks of mice
    BMC Neuroscience, 2007
    Co-Authors: Vikrant Kapoor, Nathaniel N. Urban
    Abstract:

    It has been speculated that the olfactory bulb encodes information in the form of stimulus specific activity patterns. One of the key features of this population activity is the emergence of odor-specific spatial patterns of Mitral Cell spiking over a time course of 200–800 ms following stimulus (-odor) onset. We are interested in understanding the mechanisms involved in establishing and maintaining these spatial patterns. Here, we investigated the temporal response characteristics of granule Cell activity by imaging activity in populations of olfactory bulb Cells following bulk loading of calcium dye in olfactory bulb slices. We found that granule Cells show varied (ranging from 0–900 ms) but reliable activation latencies (std. dev. = 50 ms). Moreover, we found that these activity patterns played a significant role in the generation and the maintenance of reliable spike patterns in Mitral Cells. Experiments in which multiple glomeruli were stimulated showed that the latency of granule Cell activity is input specific and that individual granule Cells respond most reliably to specific temporal patterns of stimulation. These data suggest that glomerular (~stimulus) identity is encoded in the form of latencies of granule Cells activity, which in turn results in distinct stimulus specific changes in the pattern of Mitral Cell activity.

  • reciprocal intraglomerular excitation and intra and interglomerular lateral inhibition between mouse olfactory bulb Mitral Cells
    The Journal of Physiology, 2002
    Co-Authors: Nathaniel N. Urban, Bert Sakmann
    Abstract:

    How patterns of odour-evoked glomerular activity are transformed into patterns of Mitral Cell action potentials (APs) in the olfactory bulb is determined by the functional connectivity of the Cell populations in the bulb. We have used paired whole-Cell voltage recordings from olfactory bulb slices to compare the functional connectivity of Mitral Cells to the known anatomy of the Mitral Cell network. Both inhibitory and excitatory coupling were observed between pairs of Mitral Cells. Inhibitory coupling was seen as an increased frequency of small, asynchronous GABAergic IPSPs following APs in the presynaptic Cell. Excitatory coupling was short in latency, beginning about 1.3 ms after the presynaptic AP and was mediated by both NMDA and AMPA receptors. Mitral Cell pairs were coupled by excitation if and only if their apical dendrites terminated in the same glomerulus. The excitatory coupling between Mitral Cells resembles conventional fast synaptic transmission in its time course, amplitude and latency, despite the absence of evidence for anatomically defined synapses between Mitral Cells.

Michael T. Shipley - One of the best experts on this subject based on the ideXlab platform.

  • norepinephrine increases rat Mitral Cell excitatory responses to weak olfactory nerve input via alpha 1 receptors in vitro
    Neuroscience, 1999
    Co-Authors: Kelly J Ciombor, Matthew Ennis, Michael T. Shipley
    Abstract:

    A rat olfactory bulb in vitro slice preparation was used to investigate the actions of norepinephrine on spontaneous and afferent (olfactory nerve) evoked activity of Mitral Cells. Single olfactory nerve shocks elicited a characteristic Mitral Cell response consisting of distinct, early and late spiking components separated by a brief inhibitory epoch. Bath-applied norepinephrine (1 μM) increased the early spiking component elicited by perithreshold (79% increase, P 0.05), intensity olfactory nerve shocks. The facilitatory effect of norepinephrine was due to a reduction in the incidence of response failures to perithreshold intensity shocks. Norepinephrine also decreased the inhibitory epoch separating the early and late spiking components by 44% (P<0.05). By contrast, norepinephrine had no consistent effect on the spontaneous discharge rate of the Mitral Cells. The effects of norepinephrine were mimicked by the α1 receptor agonist phenylephrine (1 μM, P<0.001). Both norepinephrine and phenylephrine modulation of Mitral Cell responses were blocked by the α1 adrenergic antagonist WB-4101 (1 μM). These findings are consistent with observations that the main olfactory bulb exhibits the highest density of α1 receptors in the brain. The α2 receptor agonist clonidine (100 nM) and the β receptor agonist isoproterenol (1 μM) had inconsistent effects on Mitral Cell spontaneous and olfactory nerve-evoked activity. These results indicate that norepinephrine increases Mitral Cell excitatory responses to weak but not strong olfactory nerve inputs in vitro via activation of α1 receptors. This is consistent with recent findings in vivo that synaptically released norepinephrine preferentially increases Mitral Cell excitatory responses to weak olfactory nerve inputs. Taken together, these results suggest that the release of norepinephrine in the olfactory bulb may increase the sensitivity of Mitral Cells to weak odors. Olfactory cues evoke norepinephrine release in the main olfactory bulb, and norepinephrine plays important roles in early olfactory learning and reproductive/maternal behaviors. By increasing Mitral Cell responses to olfactory nerve input, norepinephrine may play a critical role in modulating olfactory function, including formation and/or recall of specific olfactory memories.

  • norepinephrine increases rat Mitral Cell excitatory responses to weak olfactory nerve input via alpha 1 receptors in vitro
    Neuroscience, 1999
    Co-Authors: Kelly J Ciombor, Matthew Ennis, Michael T. Shipley
    Abstract:

    A rat olfactory bulb in vitro slice preparation was used to investigate the actions of norepinephrine on spontaneous and afferent (olfactory nerve) evoked activity of Mitral Cells. Single olfactory nerve shocks elicited a characteristic Mitral Cell response consisting of distinct, early and late spiking components separated by a brief inhibitory epoch. Bath-applied norepinephrine (1 microM) increased the early spiking component elicited by perithreshold (79% increase, P 0.05), intensity olfactory nerve shocks. The facilitatory effect of norepinephrine was due to a reduction in the incidence of response failures to perithreshold intensity shocks. Norepinephrine also decreased the inhibitory epoch separating the early and late spiking components by 44% (P<0.05). By contrast, norepinephrine had no consistent effect on the spontaneous discharge rate of the Mitral Cells. The effects of norepinephrine were mimicked by the al receptor agonist phenylephrine (1 microM, P<0.001). Both norepinephrine and phenylephrine modulation of Mitral Cell responses were blocked by the al adrenergic antagonist WB-4101 (1 microM). These findings are consistent with observations that the main olfactory bulb exhibits the highest density of alpha1 receptors in the brain. The alpha2 receptor agonist clonidine (100 nM) and the beta receptor agonist isoproterenol (1 microM) had inconsistent effects on Mitral Cell spontaneous and olfactory nerve-evoked activity. These results indicate that norepinephrine increases Mitral Cell excitatory responses to weak but not strong olfactory nerve inputs in vitro via activation of al receptors. This is consistent with recent findings in vivo that synaptically released norepinephrine preferentially increases Mitral Cell excitatory responses to weak olfactory nerve inputs. Taken together, these results suggest that the release of norepinephrine in the olfactory bulb may increase the sensitivity of Mitral Cells to weak odors. Olfactory cues evoke norepinephrine release in the main olfactory bulb, and norepinephrine plays important roles in early olfactory learning and reproductive/maternal behaviors. By increasing Mitral Cell responses to olfactory nerve input, norepinephrine may play a critical role in modulating olfactory function, including formation and/or recall of specific olfactory memories.

  • glomerular synaptic responses to olfactory nerve input in rat olfactory bulb slices
    Neuroscience, 1997
    Co-Authors: Vassiliki Aroniadouanderjaska, Matthew Ennis, Michael T. Shipley
    Abstract:

    Abstract In olfactory bulb slices from young rats, the field potential evoked in the glomerular layer by stimulation in the olfactory nerve layer consisted of two negative components: an early component (N1) which was blocked by bath application of the kainate/amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10  μ M), and a late, prolonged component (N2; duration ≥350 msec) which was unaffected by CNQX, was enhanced by reduction of Mg 2+ in the medium, and was blocked by the N -methyl- d -aspartate receptor antagonist dl -2-amino-5-phosphonovalerate (50  μ M). A comparison of the glomerular field potentials before and after knife cuts that isolated the glomerular layer from the deeper layers of the olfactory bulb indicated that both N1 and N2 were produced by currents generated, for the most part, within the glomeruli. A laminar analysis of the field potential profiles evoked by olfactory nerve stimulation in standard medium, or in the presence of CNQX, showed that N1 and N2 reversed polarity in the external plexiform and Mitral Cell layers, suggesting that both components reflected synaptic responses in the distal, apical dendrites of Mitral/tufted Cells. Simultaneous field potential recordings in the glomerular layer and intraCellular recordings in the Mitral Cell layer showed that: (i) N1 is associated with a brief, short-latency spiking activity of Mitral Cells, and (ii) N2 is associated with prolonged Mitral Cell spiking, since N2 and the late Cell firing had similar time-courses, and both were blocked by bath applied dl -2-amino-5-phosphonovalerate. Application of the GABA A receptor antagonist bicuculline methiodide (10  μ M) to standard medium selectively enhanced N2. The enhanced N2 was significantly reduced by dl -2-amino-5-phosphonovalerate. Strychnine, an antagonist of glycine receptors, had similar effects to those of bicuculline, but only at high concentrations that have been previously shown to block GABA A receptors; at low concentrations strychnine had no effect. The effects of all drugs tested were reversible. In the rat olfactory bulb, activation of the olfactory nerve evokes a kainate/AMPA receptor-mediated response in the distal, apical dendrites of Mitral/tufted Cells, followed by a slow N -methyl- d -aspartate receptor-mediated response which triggers prolonged discharge of Mitral Cells. GABA A receptor-mediated inhibition appears to suppress, preferentially, this N -methyl- d -aspartate receptor-mediated component. The presence of prolonged N -methyl- d -aspartate receptor-mediated postsynaptic activity at the primary synapses of the olfactory system may play a key role in olfactory processing by facilitating synaptic integration and plasticity.

  • activation of locus coeruleus enhances the responses of olfactory bulb Mitral Cells to weak olfactory nerve input
    The Journal of Neuroscience, 1996
    Co-Authors: Maorong Jiang, Lee A. Zimmer, Matthew Ennis, Edwin R Griff, Michael T. Shipley
    Abstract:

    The main olfactory bulb (MOB) receives a dense projection from the pontine nucleus locus coeruleus (LC), the largest collection of norepinephrine (NE)-containing Cells in the brain. LC is the sole source of NE innervation of MOB. Previous studies of the actions of exogenously applied NE on Mitral Cells, the principal output neurons of MOB, are contradictory. The effect of synaptically released NE on Mitral Cell activity is not known, nor is the influence of NE on responses of Mitral Cells to olfactory nerve inputs. The goal of the present study was to assess the influence of LC activation on spontaneous and olfactory nerve-evoked activity of Mitral Cells. In methoxyflurane-anesthetized rats, intracoerulear microinfusions of acetylcholine (ACh) (200 mm; 90–120 nl) evoked a four- to fivefold increase in LC neuronal discharge, and a transient EEG desynchronization and decrease in Mitral Cell discharge. LC activation increased excitatory responses of Mitral Cells evoked by weak (i.e., perithreshold) nasal epithelium shocks (1.0 Hz) in 17/18 Cells (mean increase = 67%). The discharge rate of Mitral Cells at the time that epithelium-evoked responses were increased did not differ significantly from pre-LC activation baseline values. Thus, changes in Mitral baseline activity do not account for the increased response to epithelium stimulation. These findings suggest that increased activity in LC–NE projections to MOB may enhance detection of relatively weak odors.

Matthew Ennis - One of the best experts on this subject based on the ideXlab platform.

  • regulation of main olfactory bulb Mitral Cell excitability by metabotropic glutamate receptor mglur1
    Journal of Neurophysiology, 2004
    Co-Authors: Thomas Heinbockel, Philip M Heyward, Francois Conquet, Matthew Ennis
    Abstract:

    In the rodent main olfactory bulb (MOB), Mitral Cells (MCs) express high levels of the group I metabotropic glutamate receptor (mGluR) subtype, mGluR1. The significance of this receptor in modulating MC excitability is unknown. We investigated the physiological role of mGluR1 in regulating MC activity in rat and mouse MOB slices. The selective group I agonist (RS)-3,5-dihydroxyphenylglycine (DHPG), but not group II or III agonists, induced potent, dose-dependent, and reversible depolarization and increased firing of MCs. These effects persisted in the presence of blockers of fast synaptic transmission, indicating that they are due to direct activation of mGluRs on MCs. Voltage-clamp recordings showed that DHPG elicited a voltage-dependent inward current consisting of multiple components sensitive to potassium and calcium channel blockade and intraCellular calcium chelation. MC excitatory responses to DHPG were absent in mGluR1 knockout mice but persisted in mGluR5 knockout mice. Broad-spectrum LY341495, MCPG, as well as preferential mGluR1 LY367385 antagonists blocked the excitatory effects of DHPG and also potently modulated MC spontaneous and olfactory nerve-evoked excitability. mGluR antagonists altered spontaneous membrane potential bistability, increasing the duration of the up and down states. mGluR antagonists also substantially attenuated MC responses to sensory input, decreasing the probability and increasing the latency of olfactory nerve-evoked spikes. These findings suggest that endogenous glutamate tonically modulates MC excitability and responsiveness to olfactory nerve input, and hence the operation of the MOB circuitry, via activation of mGluR1.

  • norepinephrine increases rat Mitral Cell excitatory responses to weak olfactory nerve input via alpha 1 receptors in vitro
    Neuroscience, 1999
    Co-Authors: Kelly J Ciombor, Matthew Ennis, Michael T. Shipley
    Abstract:

    A rat olfactory bulb in vitro slice preparation was used to investigate the actions of norepinephrine on spontaneous and afferent (olfactory nerve) evoked activity of Mitral Cells. Single olfactory nerve shocks elicited a characteristic Mitral Cell response consisting of distinct, early and late spiking components separated by a brief inhibitory epoch. Bath-applied norepinephrine (1 μM) increased the early spiking component elicited by perithreshold (79% increase, P 0.05), intensity olfactory nerve shocks. The facilitatory effect of norepinephrine was due to a reduction in the incidence of response failures to perithreshold intensity shocks. Norepinephrine also decreased the inhibitory epoch separating the early and late spiking components by 44% (P<0.05). By contrast, norepinephrine had no consistent effect on the spontaneous discharge rate of the Mitral Cells. The effects of norepinephrine were mimicked by the α1 receptor agonist phenylephrine (1 μM, P<0.001). Both norepinephrine and phenylephrine modulation of Mitral Cell responses were blocked by the α1 adrenergic antagonist WB-4101 (1 μM). These findings are consistent with observations that the main olfactory bulb exhibits the highest density of α1 receptors in the brain. The α2 receptor agonist clonidine (100 nM) and the β receptor agonist isoproterenol (1 μM) had inconsistent effects on Mitral Cell spontaneous and olfactory nerve-evoked activity. These results indicate that norepinephrine increases Mitral Cell excitatory responses to weak but not strong olfactory nerve inputs in vitro via activation of α1 receptors. This is consistent with recent findings in vivo that synaptically released norepinephrine preferentially increases Mitral Cell excitatory responses to weak olfactory nerve inputs. Taken together, these results suggest that the release of norepinephrine in the olfactory bulb may increase the sensitivity of Mitral Cells to weak odors. Olfactory cues evoke norepinephrine release in the main olfactory bulb, and norepinephrine plays important roles in early olfactory learning and reproductive/maternal behaviors. By increasing Mitral Cell responses to olfactory nerve input, norepinephrine may play a critical role in modulating olfactory function, including formation and/or recall of specific olfactory memories.

  • norepinephrine increases rat Mitral Cell excitatory responses to weak olfactory nerve input via alpha 1 receptors in vitro
    Neuroscience, 1999
    Co-Authors: Kelly J Ciombor, Matthew Ennis, Michael T. Shipley
    Abstract:

    A rat olfactory bulb in vitro slice preparation was used to investigate the actions of norepinephrine on spontaneous and afferent (olfactory nerve) evoked activity of Mitral Cells. Single olfactory nerve shocks elicited a characteristic Mitral Cell response consisting of distinct, early and late spiking components separated by a brief inhibitory epoch. Bath-applied norepinephrine (1 microM) increased the early spiking component elicited by perithreshold (79% increase, P 0.05), intensity olfactory nerve shocks. The facilitatory effect of norepinephrine was due to a reduction in the incidence of response failures to perithreshold intensity shocks. Norepinephrine also decreased the inhibitory epoch separating the early and late spiking components by 44% (P<0.05). By contrast, norepinephrine had no consistent effect on the spontaneous discharge rate of the Mitral Cells. The effects of norepinephrine were mimicked by the al receptor agonist phenylephrine (1 microM, P<0.001). Both norepinephrine and phenylephrine modulation of Mitral Cell responses were blocked by the al adrenergic antagonist WB-4101 (1 microM). These findings are consistent with observations that the main olfactory bulb exhibits the highest density of alpha1 receptors in the brain. The alpha2 receptor agonist clonidine (100 nM) and the beta receptor agonist isoproterenol (1 microM) had inconsistent effects on Mitral Cell spontaneous and olfactory nerve-evoked activity. These results indicate that norepinephrine increases Mitral Cell excitatory responses to weak but not strong olfactory nerve inputs in vitro via activation of al receptors. This is consistent with recent findings in vivo that synaptically released norepinephrine preferentially increases Mitral Cell excitatory responses to weak olfactory nerve inputs. Taken together, these results suggest that the release of norepinephrine in the olfactory bulb may increase the sensitivity of Mitral Cells to weak odors. Olfactory cues evoke norepinephrine release in the main olfactory bulb, and norepinephrine plays important roles in early olfactory learning and reproductive/maternal behaviors. By increasing Mitral Cell responses to olfactory nerve input, norepinephrine may play a critical role in modulating olfactory function, including formation and/or recall of specific olfactory memories.

  • glomerular synaptic responses to olfactory nerve input in rat olfactory bulb slices
    Neuroscience, 1997
    Co-Authors: Vassiliki Aroniadouanderjaska, Matthew Ennis, Michael T. Shipley
    Abstract:

    Abstract In olfactory bulb slices from young rats, the field potential evoked in the glomerular layer by stimulation in the olfactory nerve layer consisted of two negative components: an early component (N1) which was blocked by bath application of the kainate/amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10  μ M), and a late, prolonged component (N2; duration ≥350 msec) which was unaffected by CNQX, was enhanced by reduction of Mg 2+ in the medium, and was blocked by the N -methyl- d -aspartate receptor antagonist dl -2-amino-5-phosphonovalerate (50  μ M). A comparison of the glomerular field potentials before and after knife cuts that isolated the glomerular layer from the deeper layers of the olfactory bulb indicated that both N1 and N2 were produced by currents generated, for the most part, within the glomeruli. A laminar analysis of the field potential profiles evoked by olfactory nerve stimulation in standard medium, or in the presence of CNQX, showed that N1 and N2 reversed polarity in the external plexiform and Mitral Cell layers, suggesting that both components reflected synaptic responses in the distal, apical dendrites of Mitral/tufted Cells. Simultaneous field potential recordings in the glomerular layer and intraCellular recordings in the Mitral Cell layer showed that: (i) N1 is associated with a brief, short-latency spiking activity of Mitral Cells, and (ii) N2 is associated with prolonged Mitral Cell spiking, since N2 and the late Cell firing had similar time-courses, and both were blocked by bath applied dl -2-amino-5-phosphonovalerate. Application of the GABA A receptor antagonist bicuculline methiodide (10  μ M) to standard medium selectively enhanced N2. The enhanced N2 was significantly reduced by dl -2-amino-5-phosphonovalerate. Strychnine, an antagonist of glycine receptors, had similar effects to those of bicuculline, but only at high concentrations that have been previously shown to block GABA A receptors; at low concentrations strychnine had no effect. The effects of all drugs tested were reversible. In the rat olfactory bulb, activation of the olfactory nerve evokes a kainate/AMPA receptor-mediated response in the distal, apical dendrites of Mitral/tufted Cells, followed by a slow N -methyl- d -aspartate receptor-mediated response which triggers prolonged discharge of Mitral Cells. GABA A receptor-mediated inhibition appears to suppress, preferentially, this N -methyl- d -aspartate receptor-mediated component. The presence of prolonged N -methyl- d -aspartate receptor-mediated postsynaptic activity at the primary synapses of the olfactory system may play a key role in olfactory processing by facilitating synaptic integration and plasticity.

  • activation of locus coeruleus enhances the responses of olfactory bulb Mitral Cells to weak olfactory nerve input
    The Journal of Neuroscience, 1996
    Co-Authors: Maorong Jiang, Lee A. Zimmer, Matthew Ennis, Edwin R Griff, Michael T. Shipley
    Abstract:

    The main olfactory bulb (MOB) receives a dense projection from the pontine nucleus locus coeruleus (LC), the largest collection of norepinephrine (NE)-containing Cells in the brain. LC is the sole source of NE innervation of MOB. Previous studies of the actions of exogenously applied NE on Mitral Cells, the principal output neurons of MOB, are contradictory. The effect of synaptically released NE on Mitral Cell activity is not known, nor is the influence of NE on responses of Mitral Cells to olfactory nerve inputs. The goal of the present study was to assess the influence of LC activation on spontaneous and olfactory nerve-evoked activity of Mitral Cells. In methoxyflurane-anesthetized rats, intracoerulear microinfusions of acetylcholine (ACh) (200 mm; 90–120 nl) evoked a four- to fivefold increase in LC neuronal discharge, and a transient EEG desynchronization and decrease in Mitral Cell discharge. LC activation increased excitatory responses of Mitral Cells evoked by weak (i.e., perithreshold) nasal epithelium shocks (1.0 Hz) in 17/18 Cells (mean increase = 67%). The discharge rate of Mitral Cells at the time that epithelium-evoked responses were increased did not differ significantly from pre-LC activation baseline values. Thus, changes in Mitral baseline activity do not account for the increased response to epithelium stimulation. These findings suggest that increased activity in LC–NE projections to MOB may enhance detection of relatively weak odors.

Debra Ann Fadool - One of the best experts on this subject based on the ideXlab platform.

  • the incretin hormone glucagon like peptide 1 increases Mitral Cell excitability by decreasing conductance of a voltage dependent potassium channel
    The Journal of Physiology, 2016
    Co-Authors: Nicolas Thiebaud, Frank Reimann, Stefan Trapp, Fiona M Gribble, Ida J Llewellynsmith, Debra Ann Fadool
    Abstract:

    KEY POINTS: The gut hormone called glucagon-like peptide 1 (GLP-1) is a strong moderator of energy homeostasis and communication between the peripheral organs and the brain. GLP-1 signalling occurs in the brain; using a newly developed genetic reporter line of mice, we have discovered GLP-synthesizing Cells in the olfactory bulb. GLP-1 increases the firing frequency of neurons (Mitral Cells) that encode olfactory information by decreasing activity of voltage-dependent K channels (Kv1.3). Modifying GLP-1 levels, either therapeutically or following the ingestion of food, could alter the excitability of neurons in the olfactory bulb in a nutrition or energy state-dependent manner to influence olfactory detection or metabolic sensing. The results of the present study uncover a new function for an olfactory bulb neuron (deep short axon Cells, Cajal Cells) that could be capable of modifying Mitral Cell activity through the release of GLP-1. This might be of relevance for the action of GLP-1 mimetics now widely used in the treatment of diabetes. ABSTRACT: The olfactory system is intricately linked with the endocrine system where it may serve as a detector of the internal metabolic state or energy homeostasis in addition to its classical function as a sensor of external olfactory information. The recent development of transgenic mGLU-yellow fluorescent protein mice that express a genetic reporter under the control of the preproglucagon reporter suggested the presence of the gut hormone, glucagon-like peptide (GLP-1), in deep short axon Cells (Cajal Cells) of the olfactory bulb and its neuromodulatory effect on Mitral Cell (MC) first-order neurons. A MC target for the peptide was determined using GLP-1 receptor binding assays, immunocytochemistry for the receptor and injection of fluorescence-labelled GLP-1 analogue exendin-4. Using patch clamp recording of olfactory bulb slices in the whole-Cell configuration, we report that GLP-1 and its stable analogue exendin-4 increase the action potential firing frequency of MCs by decreasing the interburst interval rather than modifying the action potential shape, train length or interspike interval. GLP-1 decreases Kv1.3 channel contribution to outward currents in voltage clamp recordings as determined by pharmacological blockade of Kv1.3 or utilizing mice with Kv1.3 gene-targeted deletion as a negative control. Because fluctuations in GLP-1 concentrations monitored by the olfactory bulb can modify the firing frequency of MCs, olfactory coding could change depending upon nutritional or physiological state. As a regulator of neuronal activity, GLP-1 or its analogue may comprise a new metabolic factor with a potential therapeutic target in the olfactory bulb (i.e. via intranasal delivery) for controlling an imbalance in energy homeostasis.

  • olfactory sensory deprivation increases the number of probdnf immunoreactive Mitral Cells in the olfactory bulb of mice
    Neuroscience Letters, 2008
    Co-Authors: K C Biju, Thomas G Mast, Debra Ann Fadool
    Abstract:

    In the olfactory bulb, apoptotic Cell-death induced by sensory deprivation is restricted to interneurons in the glomerular and granule Cell layers, and to a lesser extent in the external plexiform layer, whereas Mitral Cells do not typically undergo apoptosis. With the goal to understand whether brain-derived neurotrophic factor (BDNF) mediates Mitral Cell survival, we performed unilateral naris occlusion on mice at postnatal day one (P1) and examined the subsequent BDNF-immunoreactive (BDNF-ir) profile of the olfactory bulb at P20, P30, and P40. Ipsilateral to the naris occlusion, there was a significant increase in the number of BDNF-ir Mitral Cells per unit area that was independent of the duration of the sensory deprivation induced by occlusion. The number of BDNF-ir juxtaglomerular Cells per unit area, however, was clearly diminished. Western blot analysis revealed the presence of primarily proBDNF in the olfactory bulb. These data provide evidence for a neurotrophic role of proBDNF in the olfactory system of mice and suggest that proBDNF may act to protect Mitral Cells from the effects of apoptotic changes induced by odor sensory deprivation.

Bert Sakmann - One of the best experts on this subject based on the ideXlab platform.

  • reciprocal intraglomerular excitation and intra and interglomerular lateral inhibition between mouse olfactory bulb Mitral Cells
    The Journal of Physiology, 2002
    Co-Authors: Nathaniel N. Urban, Bert Sakmann
    Abstract:

    How patterns of odour-evoked glomerular activity are transformed into patterns of Mitral Cell action potentials (APs) in the olfactory bulb is determined by the functional connectivity of the Cell populations in the bulb. We have used paired whole-Cell voltage recordings from olfactory bulb slices to compare the functional connectivity of Mitral Cells to the known anatomy of the Mitral Cell network. Both inhibitory and excitatory coupling were observed between pairs of Mitral Cells. Inhibitory coupling was seen as an increased frequency of small, asynchronous GABAergic IPSPs following APs in the presynaptic Cell. Excitatory coupling was short in latency, beginning about 1.3 ms after the presynaptic AP and was mediated by both NMDA and AMPA receptors. Mitral Cell pairs were coupled by excitation if and only if their apical dendrites terminated in the same glomerulus. The excitatory coupling between Mitral Cells resembles conventional fast synaptic transmission in its time course, amplitude and latency, despite the absence of evidence for anatomically defined synapses between Mitral Cells.

  • action potential propagation in Mitral Cell lateral dendrites is decremental and controls recurrent and lateral inhibition in the mammalian olfactory bulb
    Proceedings of the National Academy of Sciences of the United States of America, 2001
    Co-Authors: Troy W Margrie, Bert Sakmann, Nathaniel N. Urban
    Abstract:

    In the mammalian main olfactory bulb (MOB), the release of glutamate from lateral dendrites of Mitral Cells onto the dendrites of granule Cells evokes recurrent and lateral inhibition of Mitral Cell activity. Whole-Cell voltage recordings in the mouse MOB in vivo and in vitro show that recurrent and lateral inhibition together control the number, duration, and onset of odor-evoked action potential (AP) firing in Mitral Cells. APs in Mitral Cells propagate into the lateral dendrites and evoke a transient increase in dendritic calcium concentration ([Ca2+]), which is decremental with distance from the soma, and increases with AP number. These results suggest that the extent of AP propagation in lateral dendrites of Mitral Cells, along with the concomitant dendritic Ca2+ transient, controls the amplitude of lateral and recurrent inhibition and thus is a critical determinant of odor-specific AP patterns in the MOB.