Analysis of Relations between NMDA Receptors and GABA Release at Olfactory Bulb Reciprocal Synapses

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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Physiological Properties of Late Inspiratory Neurons and Their Possible Involvement in Inspiratory Off-Switching in Cats

Journal of Neurophysiology ◽

10.1152/jn.00470.2001 ◽

2002 ◽

Vol 87 (2) ◽

pp. 1057-1067 ◽

Cited By ~ 29

Author(s):

Akira Haji ◽

Mari Okazaki ◽

Hiromi Yamazaki ◽

Ryuji Takeda

Keyword(s):

Nmda Receptors ◽

Gaba Release ◽

Membrane Depolarization ◽

Inhibitory Neurons ◽

Acid Decarboxylase ◽

Postsynaptic Potentials ◽

Inspiratory Neurons ◽

Small Constant ◽

Physiological Properties ◽

Decerebrate Cats

To assess the functional significance of late inspiratory (late-I) neurons in inspiratory off-switching (IOS), membrane potential and discharge properties were examined in vagotomized, decerebrate cats. During spontaneous IOS, late-I neurons displayed large membrane depolarization and associated discharge of action potentials that started in late inspiration, peaked at the end of inspiration, and ended during postinspiration. Depolarization was decreased by iontophoresis of dizocilpine and eliminated by tetrodotoxin. Stimulation of the vagus nerve or the nucleus parabrachialis medialis (NPBM) also evoked depolarization of late-I neurons and IOS. Waves of spontaneous chloride-dependent inhibitory postsynaptic potentials (IPSPs) preceded membrane depolarization during early inspiration and followed during postinspiration and stage 2 expiration of the respiratory cycle. Iontophoresed bicuculline depressed the IPSPs. Intravenous dizocilpine caused a greatly prolonged inspiratory discharge of the phrenic nerve (apneusis) and suppressed late-inspiratory depolarization as well as early-inspiratory IPSPs, resulting in a small constant depolarization throughout the apneusis. NPBM or vagal stimulation after dizocilpine produced small, stimulus-locked excitatory postsynaptic potentials (EPSPs) in late-I neurons. Neurobiotin-labeled late-I neurons revealed immunoreactivity for glutamic acid decarboxylase as well as N-methyl-d-aspartate (NMDA) receptors. These results suggest that late-I neurons are GABAergic inhibitory neurons, while the effects of bicuculline and dizocilpine indicate that they receive periodic waves of GABAergic IPSPs and glutamatergic EPSPs. The data lead to the conclusion that late-I neurons play an important inhibitory role in IOS. NMDA receptors are assumed to augment and/or synchronize late-inspiratory depolarization and discharge of late-I neurons, leading to GABA release and consequently off-switching of bulbar inspiratory neurons and phrenic motoneurons.

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GABA release triggered by the activation of neuron-like non-NMDA receptors in cultured type 2 astrocytes is carrier-mediated

Glia ◽

10.1002/glia.440040302 ◽

1991 ◽

Vol 4 (3) ◽

pp. 245-255 ◽

Cited By ~ 58

Author(s):

Vittorio Gallo ◽

Mario Patrizio ◽

Giulio Levi

Keyword(s):

Nmda Receptors ◽

Gaba Release

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

Journal of Neurophysiology ◽

10.1152/jn.00925.2017 ◽

2018 ◽

Vol 120 (4) ◽

pp. 2036-2048 ◽

Cited By ~ 1

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.

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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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Mechanisms governing dendritic gamma -aminobutyric acid (GABA) release in the rat olfactory bulb

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.021445798 ◽

2000 ◽

Vol 98 (1) ◽

pp. 337-342 ◽

Cited By ~ 32

Author(s):

J. S. Isaacson

Keyword(s):

Olfactory Bulb ◽

Gaba Release ◽

Aminobutyric Acid ◽

Gamma Aminobutyric Acid

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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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