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

2020 ◽  
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.

scholarly journals A dominant role for the beta 4 nicotinic receptor subunit in nicotinic modulation of glomerular microcircuits in the mouse olfactory bulb

2018 ◽  
Vol 120 (4) ◽  
pp. 2036-2048 ◽  
Author(s):  
Michael S. Spindle ◽  
Pirooz V. Parsa ◽  
Spencer G. Bowles ◽  
Rinaldo D. D’Souza ◽  
Sukumar Vijayaraghavan
Keyword(s):  
Olfactory Bulb ◽  
Nicotinic Acetylcholine Receptors ◽  
Information Transfer ◽  
Time Course ◽  
Feedback Inhibition ◽  
Dominant Role ◽  
Receptor Gene ◽  
Gaba Release ◽  
Cell Types ◽  
Receptor Activation

Nicotinic acetylcholine receptors (nAChRs) regulate information transfer across the main olfactory bulb by instituting a high-pass intensity filter allowing for the filtering out of weak inputs. Excitation-driven inhibition of the glomerular microcircuit via GABA release from periglomerular cells appears to underlie this effect of nAChR activation. The multiplicity of nAChR subtypes and cellular locations raises questions about their respective roles in mediating their effects on the glomerular output. In this study, we address this issue by targeting heteromeric nAChRs using receptor knockouts (KOs) for the two dominant nAChR β-subunit genes known to be expressed in the central nervous system. KOs of the β2-nAChR subunit did not affect nAChR currents from mitral cells (MCs) but attenuated those from the external tufted (ET) cells. In slices from these animals, activation of nAChRs still effectively inhibited excitatory postsynaptic currents (EPSCs) and firing on MCs evoked by the olfactory nerve (ON) stimulation, thereby indicating that the filter mechanism was intact. On the other hand, recordings from β4-KOs showed that nAChR responses from MCs were abolished and those from ET cells were attenuated. Excitation-driven feedback was abolished as was the effect of nAChR activation on ON-evoked EPSCs. Experiments using calcium imaging showed that one possible consequence of the β2-subunit activation might be to alter the time course of calcium transients in juxtaglomerular neurons suggesting a role for these receptors in calcium signaling. Our results indicate that nAChRs containing the β4-subunit are critical in the filtering of odor inputs and play a determinant role in the cholinergic modulation of glomerular output. NEW & NOTEWORTHY In this study, using receptor gene knockouts we examine the relative contributions of heteromeric nAChR subtypes located on different cell types to this effect of receptor activation. Our results demonstrate that nAChRs containing the β4-subunit activate MCs resulting in feedback inhibition from glomerular interneurons. This period of inhibition results in the selective filtering of weak odor inputs providing one mechanism by which nAChRs can enhance discrimination between two closely related odors.

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

2009 ◽  
Vol 101 (4) ◽  
pp. 2052-2061 ◽  
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.

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

2015 ◽  
Vol 113 (4) ◽  
pp. 1234-1248 ◽  
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.

scholarly journals Spatial structure of synchronized inhibition in the olfactory bulb

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.

scholarly journals Local Postsynaptic Signaling on Slow Time Scales in Reciprocal Olfactory Bulb Granule Cell Spines Matches Asynchronous Release

2020 ◽  
Vol 12 ◽  
Author(s):  
Tiffany Ona Jodar ◽  
Vanessa Lage-Rupprecht ◽  
Nixon M. Abraham ◽  
Christine R. Rose ◽  
Veronica Egger
Keyword(s):  
Olfactory Bulb ◽  
Time Scales ◽  
Granule Cell ◽  
Slow Time ◽  
Asynchronous Release

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

eLife ◽  
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.

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

2003 ◽  
Vol 90 (3) ◽  
pp. 1921-1935 ◽  
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.

scholarly journals Calcium Influx through NMDA Receptors Directly Evokes GABA Release in Olfactory Bulb Granule Cells

2000 ◽  
Vol 20 (13) ◽  
pp. 5124-5134 ◽  
Author(s):  
Brian Halabisky ◽  
Daniel Friedman ◽  
Milan Radojicic ◽  
Ben W. Strowbridge
Keyword(s):  
Olfactory Bulb ◽  
Nmda Receptors ◽  
Granule Cells ◽  
Calcium Influx ◽  
Gaba Release

scholarly journals Target-specific control of olfactory bulb periglomerular cells by GABAergic and cholinergic basal forebrain inputs

2021 ◽  
Author(s):  
Didier Desaintjan
Keyword(s):  
Olfactory Bulb ◽  
Basal Forebrain ◽  
Internal State ◽  
Low Frequency ◽  
Gaba Release ◽  
Patch Clamp Recording ◽  
Cholinergic Basal Forebrain ◽  
Adult Mice ◽  
Whole Cell Patch Clamp ◽  
M1 Muscarinic

The olfactory bulb (OB), the first relay for odor processing, receives dense GABAergic and cholinergic long-range projections from basal forebrain (BF) nuclei that provide information about the internal state and behavioral context of the animal. However, the targets, impact and dynamics of these afferents are still unclear. I studied how BF synaptic inputs modulate activity in diverse subtypes of periglomerular (PG) interneurons using optogenetic stimulation and loose cell-attached or whole-cell patch-clamp recording in OB slices from adult mice. GABAergic BF inputs potently blocked PG cells firing except in a minority of calretinin-expressing cells in which GABA release elicited spiking. Parallel cholinergic projections excited a previously overlooked PG cell subtype via synaptic activation of M1 muscarinic receptors. Low frequency stimulation of the cholinergic axons drove persistent firing in these PG cells thereby increasing tonic inhibition in principal neurons. Taken together, these findings suggest that modality-specific BF inputs can orchestrate inhibition in OB glomeruli using multiple, potentially independent, inhibitory or excitatory target-specific pathways.

scholarly journals Presynaptic NMDA receptors cooperate with local action potentials to implement activity-dependent GABA release from the reciprocal olfactory bulb granule cell spine

2018 ◽  
Author(s):  
Vanessa Lage-Rupprecht ◽  
Li Zhou ◽  
Gaia Bianchini ◽  
S. Sara Aghvami ◽  
Max Mueller ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Nmda Receptors ◽  
Granule Cells ◽  
Specific Activity ◽  
Sensory System ◽  
Gaba Release ◽  
Cooperative Action ◽  
Two Photon ◽  
Presynaptic Nmda Receptors ◽  
Activity Dependent

AbstractIn 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), i.e. 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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