Spatial structure of synchronized inhibition in the olfactory bulb

Mapping Intimacies ◽

10.1101/123695 ◽

2017 ◽

Author(s):

Hannah A. Arnson ◽

Ben W. Strowbridge

Keyword(s):

Olfactory Bulb ◽

Action Potentials ◽

Granule Cells ◽

Gaba Release ◽

Principal Cells ◽

Receptor Neurons ◽

Olfactory Bulb Slices ◽

Cortical Regions ◽

Large Groups ◽

Dendrodendritic Synapses

AbstractOlfactory sensory input is detected by receptor neurons in the nose which then send information to the olfactory bulb, the first brain region for processing olfactory information. Within the olfactory bulb, many local circuit interneurons, including axonless granule cells, function to facilitate fine odor discrimination. How interneurons interact with principal cells to affect bulbar processing is not known though the mechanism is likely to be different than in sensory cortical regions since the olfactory bulb lacks an obvious topographical organization; neighboring glomerular columns, representing inputs from different receptor neuron subtypes, typically have different odor tuning. Determining the spatial scale over which interneurons such as granule cells can affect principal cells is a critical step towards understanding how the olfactory bulb operates. We addressed this question by assaying inhibitory synchrony using intracellular recordings from pairs of principal cells with different inter-somatic spacing. We find that in acute rat olfactory bulb slices, inhibitory synchrony is evident in the spontaneous synaptic input in mitral cells separated up to 300 μm. At all inter-somatic spacing assayed, inhibitory synchrony was dependent on fast Na+ channels, suggesting that action potentials in granule cells function to coordinate GABA release at relatively distant dendrodendritic synapses formed throughout the the dendritic arbor. Our results suggest that individual granule cells are able to influence relatively large groups of mitral and tufted cells belonging to clusters of at least 15 glomerular modules, providing a potential mechanism to integrate signals reflecting a wide variety of odorants.

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Electrophysiology of Interneurons in the Glomerular Layer of the Rat Olfactory Bulb

Journal of Neurophysiology ◽

10.1152/jn.2001.86.4.1899 ◽

2001 ◽

Vol 86 (4) ◽

pp. 1899-1907 ◽

Cited By ~ 52

Author(s):

A. Rory McQuiston ◽

Lawrence C. Katz

Keyword(s):

Olfactory Bulb ◽

Action Potentials ◽

Neuronal Morphology ◽

Bursting Neurons ◽

Whole Cell Patch Clamp ◽

Physiological Properties ◽

Receptor Neurons ◽

Tufted Cells ◽

Olfactory Bulb Slices ◽

Channel Dependent

In the mammalian olfactory bulb, glomeruli are surrounded by a heterogeneous population of interneurons called juxtaglomerular neurons. As they receive direct input from olfactory receptor neurons and connect with mitral cells, they are involved in the initial stages of olfactory information processing, but little is known about their detailed physiological properties. Using whole cell patch-clamp techniques, we recorded from juxtaglomerular neurons in rat olfactory bulb slices. Based on their response to depolarizing pulses, juxtaglomerular neurons could be divided into two physiological classes: bursting and standard firing. When depolarized, the standard firing neurons exhibited a range of responses: accommodating, nonaccommodating, irregular firing, and delayed to firing patterns of action potentials. Although the firing pattern was not rigorously predictive of a particular neuronal morphology, most short axon cells fired accommodating trains of action potentials, while most delayed to firing cells were external tufted cells. In contrast to the standard firing neurons, bursting neurons produced a calcium-channel-dependent low-threshold spike when depolarized either by current injection or by spontaneous or evoked postsynaptic potentials. Bursting neurons also could oscillate spontaneously. Most bursting cells were either periglomerular cells or external tufted cells. Based on their mode of firing and placement in the bulb circuit, these bursting cells are well situated to drive synchronous oscillations in the olfactory bulb.

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Presynaptic NMDARs cooperate with local spikes toward GABA release from the reciprocal olfactory bulb granule cell spine

eLife ◽

10.7554/elife.63737 ◽

2020 ◽

Vol 9 ◽

Author(s):

Vanessa Lage-Rupprecht ◽

Li Zhou ◽

Gaia Bianchini ◽

S Sara Aghvami ◽

Max Mueller ◽

...

Keyword(s):

Olfactory Bulb ◽

Efficient Solution ◽

Granule Cells ◽

Specific Activity ◽

Sensory System ◽

Gaba Release ◽

Cooperative Action ◽

Two Photon ◽

Activity Dependent ◽

Dendrodendritic Synapses

In the rodent olfactory bulb the smooth dendrites of the principal glutamatergic mitral cells (MCs) form reciprocal dendrodendritic synapses with large spines on GABAergic granule cells (GC), where unitary release of glutamate can trigger postsynaptic local activation of voltage-gated Na+-channels (Navs), that is a spine spike. Can such single MC input evoke reciprocal release? We find that unitary-like activation via two-photon uncaging of glutamate causes GC spines to release GABA both synchronously and asynchronously onto MC dendrites. This release indeed requires activation of Navs and high-voltage-activated Ca2+-channels (HVACCs), but also of NMDA receptors (NMDAR). Simulations show temporally overlapping HVACC- and NMDAR-mediated Ca2+-currents during the spine spike, and ultrastructural data prove NMDAR presence within the GABAergic presynapse. This cooperative action of presynaptic NMDARs allows to implement synapse-specific, activity-dependent lateral inhibition, and thus could provide an efficient solution to combinatorial percept synthesis in a sensory system with many receptor channels.

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Transient Activity Induces a Long-Lasting Increase in the Excitability of Olfactory Bulb Interneurons

Journal of Neurophysiology ◽

10.1152/jn.00526.2007 ◽

2008 ◽

Vol 99 (1) ◽

pp. 187-199 ◽

Cited By ~ 8

Author(s):

Tsuyoshi Inoue ◽

Ben W. Strowbridge

Keyword(s):

Olfactory Bulb ◽

Granule Cells ◽

Receptor Activation ◽

Brain Regions ◽

Persistent Activity ◽

Cellular Mechanisms ◽

Calcium Dependent ◽

Transient Activity ◽

Olfactory Bulb Slices ◽

Processing And Storage

Little is known about the cellular mechanisms that underlie the processing and storage of sensory in the mammalian olfactory system. Here we show that persistent spiking, an activity pattern associated with working memory in other brain regions, can be evoked in the olfactory bulb by stimuli that mimic physiological patterns of synaptic input. We find that brief discharges trigger persistent activity in individual interneurons that receive slow, subthreshold oscillatory input in acute rat olfactory bulb slices. A 2- to 5-Hz oscillatory input, which resembles the synaptic drive that the olfactory bulb receives during sniffing, is required to maintain persistent firing. Persistent activity depends on muscarinic receptor activation and results from interactions between calcium-dependent afterdepolarizations and low-threshold Ca spikes in granule cells. Computer simulations suggest that intrinsically generated persistent activity in granule cells can evoke correlated spiking in reciprocally connected mitral cells. The interaction between the intrinsic currents present in reciprocally connected olfactory bulb neurons constitutes a novel mechanism for synchronized firing in subpopulations of neurons during olfactory processing.

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Presynaptic Muscarinic Receptors Enhance Glutamate Release at the Mitral/Tufted to Granule Cell Dendrodendritic Synapse in the Rat Main Olfactory Bulb

Journal of Neurophysiology ◽

10.1152/jn.90734.2008 ◽

2009 ◽

Vol 101 (4) ◽

pp. 2052-2061 ◽

Cited By ~ 20

Author(s):

Ambarish S. Ghatpande ◽

Alan Gelperin

Keyword(s):

Olfactory Bulb ◽

Granule Cell ◽

Basal Forebrain ◽

Granule Cells ◽

Calcium Influx ◽

Glutamate Release ◽

Gaba Release ◽

Cellular Mechanisms ◽

Tufted Cells

The mammalian olfactory bulb receives multiple modulatory inputs, including a cholinergic input from the basal forebrain. Understanding the functional roles played by the cholinergic input requires an understanding of the cellular mechanisms it modulates. In an in vitro olfactory bulb slice preparation we demonstrate cholinergic muscarinic modulation of glutamate release onto granule cells that results in γ-aminobutyric acid (GABA) release onto mitral/tufted cells. We demonstrate that the broad-spectrum cholinergic agonist carbachol triggers glutamate release from mitral/tufted cells that activates both AMPA and NMDA receptors on granule cells. Activation of the granule cell glutamate receptors leads to calcium influx through voltage-gated calcium channels, resulting in spike-independent, asynchronous GABA release at reciprocal dendrodendritic synapses that granule cells form with mitral/tufted cells. This cholinergic modulation of glutamate release persists through much of postnatal bulbar development, suggesting a functional role for cholinergic inputs from the basal forebrain in bulbar processing of olfactory inputs and possibly in postnatal development of the olfactory bulb.

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

Journal of Neurophysiology ◽

10.1152/jn.00594.2014 ◽

2015 ◽

Vol 113 (4) ◽

pp. 1234-1248 ◽

Cited By ~ 3

Author(s):

Mavis Irwin ◽

Ann Greig ◽

Petr Tvrdik ◽

Mary T. Lucero

Keyword(s):

Olfactory Bulb ◽

Indirect Effects ◽

Calcium Ion ◽

Gaba Receptors ◽

Sensory Input ◽

Granule Cells ◽

Gaba Release ◽

Network Activity ◽

Pituitary Adenylate Cyclase ◽

Ion Activity

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.

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Local postsynaptic signalling on slow time scales in reciprocal olfactory bulb granule cell spines matches asynchronous release

10.1101/2020.09.03.281642 ◽

2020 ◽

Cited By ~ 2

Author(s):

Tiffany Ona Jodar ◽

Vanessa Lage-Rupprecht ◽

Nixon M. Abraham ◽

Christine R. Rose ◽

Veronica Egger

Keyword(s):

Olfactory Bulb ◽

Time Scales ◽

Time Course ◽

Granule Cells ◽

Gaba Release ◽

Fluorescence Signal ◽

Slow Time ◽

Triggered Release ◽

Time To Peak ◽

Adult Mice

AbstractIn the vertebrate olfactory bulb (OB), axonless granule cells (GC) mediate self- and lateral inhibitory interactions between mitral/tufted cells via reciprocal dendrodendritic synapses. Locally triggered release of GABA from the large reciprocal GC spines occurs on both fast and slow time scales, possibly enabling parallel processing during olfactory perception. Here we investigate local mechanisms for asynchronous spine output.To reveal the temporal and spatial characteristics of postsynaptic ion transients, we imaged spine and adjacent dendrite Ca2+- and Na+-signals with minimal exogenous buffering by the respective fluorescent indicator dyes upon two-photon uncaging of DNI-glutamate in OB slices from juvenile rats. Both postsynaptic fluorescence signals decayed slowly, with average half durations in the spine head of t1/2_Δ[Ca2+]i ~500 ms and t1/2_Δ[Na+]i ~1000 ms. We also analysed the kinetics of already existing data of postsynaptic spine Ca2+-signals in response to glomerular stimulation in OB slices from adult mice, either WT or animals with partial GC glutamate receptor deletions (NMDAR: GluN1 subunit; AMPAR: GluA2 subunit). In a large subset of spines the fluorescence signal had a protracted rise time (average time to peak ~400 ms, range 20 ms - >1000 ms). This slow rise was independent of Ca2+ entry via NMDARs, since similarly slow signals occurred in ΔGluN1 GCs. Additional Ca2+ entry in ΔGluA2 GCs (with AMPARs rendered Ca2+-permeable), however, resulted in larger ΔF/Fs that rose yet more slowly.Thus GC spines appear to dispose of several local mechanisms to promote asynchronous GABA release, which are reflected in the time course of mitral/tufted cell recurrent inhibition.

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Dendrodendritic Inhibition and Simulated Odor Responses in a Detailed Olfactory Bulb Network Model

Journal of Neurophysiology ◽

10.1152/jn.00623.2002 ◽

2003 ◽

Vol 90 (3) ◽

pp. 1921-1935 ◽

Cited By ~ 59

Author(s):

Andrew P. Davison ◽

Jianfeng Feng ◽

David Brown

Keyword(s):

Experimental Data ◽

Spatial Distribution ◽

Olfactory Bulb ◽

Time Course ◽

Granule Cells ◽

Temporal Structure ◽

Network Connectivity ◽

Realistic Model ◽

Mitral Cells ◽

Dendrodendritic Synapses

In the olfactory bulb, both the spatial distribution and the temporal structure of neuronal activity appear to be important for processing odor information, but it is currently impossible to measure both of these simultaneously with high resolution and in all layers of the bulb. We have developed a biologically realistic model of the mammalian olfactory bulb, incorporating the mitral and granule cells and the dendrodendritic synapses between them, which allows us to observe the network behavior in detail. The cell models were based on previously published work. The attributes of the synapses were obtained from the literature. The pattern of synaptic connections was based on the limited experimental data in the literature on the statistics of connections between neurons in the bulb. The results of simulation experiments with electrical stimulation agree closely in most details with published experimental data. This gives confidence that the model is capturing features of network interactions in the real olfactory bulb. The model predicts that the time course of dendrodendritic inhibition is dependent on the network connectivity as well as on the intrinsic parameters of the synapses. In response to simulated odor stimulation, strongly activated mitral cells tend to suppress neighboring cells, the mitral cells readily synchronize their firing, and increasing the stimulus intensity increases the degree of synchronization. Preliminary experiments suggest that slow temporal changes in the degree of synchronization are more useful in distinguishing between very similar odorants than is the spatial distribution of mean firing rate.

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Intracellular responses of identified rat olfactory bulb interneurons to electrical and odor stimulation

Journal of Neurophysiology ◽

10.1152/jn.1990.64.3.932 ◽

1990 ◽

Vol 64 (3) ◽

pp. 932-947 ◽

Cited By ~ 83

Author(s):

D. P. Wellis ◽

J. W. Scott

Keyword(s):

Electrical Stimulation ◽

Olfactory Bulb ◽

Granule Cell ◽

Action Potentials ◽

Granule Cells ◽

Olfactory Nerve ◽

Mitral Cell ◽

Intracellular Recordings ◽

Postsynaptic Potential ◽

Stimulation Of

1. Intracellular recordings were made from 28 granule cells and 6 periglomerular cells of the rat olfactory bulb during odor stimulation and electrical stimulation of the olfactory nerve layer (ONL) and lateral olfactory tract (LOT). Neurons were identified by injection of horseradish peroxidase (HRP) or biocytin and/or intracellular response characteristics. Odorants were presented in a cyclic sniff paradigm, as reported previously. 2. All interneurons could be activated from a wide number of stimulation sites on the ONL, with distances exceeding their known dendritic spreads and the dispersion of nerve fibers within the ONL, indicating that multisynaptic pathways must also exist at the glomerular region. All types of interneurons also responded to odorant stimulation, showing a variety of responses. 3. Granule cells responded to electrical stimulation of the LOT and ONL as reported previously. However, intracellular potential, excitability, and conductance analysis suggested that the mitral cell-mediated excitatory postsynaptic potential (EPSP) is followed by a long inhibitory postsynaptic potential (IPSP). An early negative potential, before the EPSP, was also observed in every granule cell and correlated with component I of the extracellular LOT-induced field potential. We have interpreted this negativity as a "field effect," that may be diagnostic of granule cells. 4. Most granule cells exhibited excitatory responses to odorant stimulation. Odors could produce spiking responses that were either nonhabituating (response to every sniff) or rapidly habituating (response to first sniff only). Other granule cells, while spiking to electrical stimulation, showed depolarizations that did not evoke spikes to odor stimulation. These depolarizations were transient with each sniff or sustained across a series of sniffs. These physiological differences to odor stimulation correlated with granule cell position beneath the mitral cell layer for 12 cells, suggesting that morphological subtypes of granule cells may show physiological differences. Some features of the granule cell odor responses seem to correlate with some of the features we have observed in mitral/tufted cell intracellular recordings. Only one cell showed inhibition to odors. 5. Periglomerular (PG) cells showed a response to ONL stimulation that was unlike that found in other olfactory bulb neurons. There was a long-duration hyperpolarization after a spike and large depolarization or burst of spikes (20-30 ms in duration). Odor stimulation produced simple bursts of action potentials, Odor stimulation produced simple bursts of action potentials, suggesting that PG cells may simply follow input from the olfactory nerve.(ABSTRACT TRUNCATED AT 400 WORDS)

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Disruption of GABAA Receptors on GABAergic Interneurons Leads to Increased Oscillatory Power in the Olfactory Bulb Network

Journal of Neurophysiology ◽

10.1152/jn.2001.86.6.2823 ◽

2001 ◽

Vol 86 (6) ◽

pp. 2823-2833 ◽

Cited By ~ 144

Author(s):

Zoltan Nusser ◽

Leslie M. Kay ◽

Gilles Laurent ◽

Gregg E. Homanics ◽

Istvan Mody

Keyword(s):

Olfactory Bulb ◽

Granule Cells ◽

Fold Increase ◽

Network Activity ◽

Gabaergic Interneurons ◽

Synaptic Inhibition ◽

Principal Cells ◽

Network Oscillations

Synchronized neural activity is believed to be essential for many CNS functions, including neuronal development, sensory perception, and memory formation. In several brain areas GABAA receptor–mediated synaptic inhibition is thought to be important for the generation of synchronous network activity. We have used GABAA receptor β3 subunit deficient mice (β3−/−) to study the role of GABAergic inhibition in the generation of network oscillations in the olfactory bulb (OB) and to reveal the role of such oscillations in olfaction. The expression of functional GABAA receptors was drastically reduced (>93%) in β3−/− granule cells, the local inhibitory interneurons of the OB. This was revealed by a large reduction of muscimol-evoked whole-cell current and the total current mediated by spontaneous, miniature inhibitory postsynaptic currents (mIPSCs). In β3−/− mitral/tufted cells (principal cells), there was a two-fold increase in mIPSC amplitudes without any significant change in their kinetics or frequency. In parallel with the altered inhibition, there was a significant increase in the amplitude of theta (80% increase) and gamma (178% increase) frequency oscillations in β3−/− OBs recorded in vivo from freely moving mice. In odor discrimination tests, we found β3−/− mice to be initially the same as, but better with experience than β3+/+ mice in distinguishing closely related monomolecular alcohols. However, β3−/− mice were initially better and then worse with practice than control mice in distinguishing closely related mixtures of alcohols. Our results indicate that the disruption of GABAAreceptor–mediated synaptic inhibition of GABAergic interneurons and the augmentation of IPSCs in principal cells result in increased network oscillations in the OB with complex effects on olfactory discrimination, which can be explained by an increase in the size or effective power of oscillating neural cell assemblies among the mitral cells of β3−/− mice.

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