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

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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Distribution of immunoreactivity for ?-aminobutyric acid in the salamander olfactory bulb

The Journal of Comparative Neurology ◽

10.1002/cne.903190410 ◽

1992 ◽

Vol 319 (4) ◽

pp. 606-614 ◽

Cited By ~ 15

Author(s):

Kathryn A. Hamilton

Keyword(s):

Olfactory Bulb ◽

Aminobutyric Acid

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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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Neurochemical studies on γ-aminobutyric acid(GABA) receptor (XXXVI). Presynaptic regulation of GABA release from GABA terminal: Analysis using in vivo microdialysis.

The Japanese Journal of Pharmacology ◽

10.1016/s0021-5198(19)51507-4 ◽

1993 ◽

Vol 61 ◽

pp. 153

Author(s):

Tsuneichi Hashimoto ◽

Kinya Kuriyama

Keyword(s):

Gaba Receptor ◽

Gaba Release ◽

In Vivo Microdialysis ◽

Aminobutyric Acid ◽

Presynaptic Regulation

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GABA release in posterior hypothalamus across sleep-wake cycle

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1996.271.6.r1707 ◽

1996 ◽

Vol 271 (6) ◽

pp. R1707-R1712 ◽

Cited By ~ 8

Author(s):

D. Nitz ◽

J. M. Siegel

Keyword(s):

Receptor Agonist ◽

High Performance ◽

Slow Wave Sleep ◽

Gaba Release ◽

Posterior Hypothalamus ◽

Aminobutyric Acid ◽

Gamma Aminobutyric Acid ◽

Rapid Eye Movement Sleep ◽

Unit Discharge ◽

Selective Increase

The activity of neurons in the posterior hypothalamus (PH) is thought to contribute to the production of wakefulness and electroencephalograph desynchronization. Inactivation of neuronal activity in this area is known to induce sleep. Most PH neurons decrease unit discharge during slow-wave sleep (SWS) relative to wake and rapid eye movement sleep. In the present study, we sought to examine potential sources of inhibition or disfacilitation underlying the reduction of PH unit activity during SWS in the cat. We employed the microdialysis technique in conjunction with high-performance liquid chromatography methods for the quantification of glutamate, glycine, and gamma-aminobutyric acid (GABA) release. We found a selective increase in GABA release during SWS in the PH. Glutamate and glycine levels were unchanged across the sleep-wake cycle. microinjection of the GABAA-receptor agonist muscimol, into the same areas from which microdialysis samples were collected, increased SWS time. Our studies support the hypothesis that GABA release in the posterior hypothalamus mediates inhibition of posterior hypothalamic neurons, thereby facilitating SWS.

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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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Evidence that γ-Aminobutyric Acid Is Part of the Neural Circuit Mediating Estradiol Negative Feedback in Anestrous Ewes

Endocrinology ◽

10.1210/en.2007-1362 ◽

2008 ◽

Vol 149 (6) ◽

pp. 2762-2772 ◽

Cited By ~ 9

Author(s):

Adrienne L. Bogusz ◽

Steven L. Hardy ◽

Michael N. Lehman ◽

John M. Connors ◽

Stanley M. Hileman ◽

...

Keyword(s):

Negative Feedback ◽

Gaba Receptor ◽

Receptor Agonist ◽

Neural Circuit ◽

Gabab Receptor ◽

Gaba Release ◽

Aminobutyric Acid ◽

Receptor Ligands ◽

Endogenous Gaba ◽

Lh Secretion

Seasonal anestrus in ewes is driven by an increase in response to estradiol (E2) negative feedback. Compelling evidence indicates that inhibitory A15 dopaminergic (DA) neurons mediate the increased inhibitory actions of E2 in anestrus, but these neurons do not contain estrogen receptors. Therefore, we have proposed that estrogen-responsive afferents to A15 neurons are part of the neural circuit mediating E2 negative feedback in anestrus. This study examined the possible role of afferents containing γ-aminobutyric acid (GABA) and nitric oxide (NO) in modulating the activity of A15 neurons. Local administration of NO synthase inhibitors to the A15 had no effect on LH, but GABA receptor ligands produced dramatic changes. Administration of either a GABAA or GABAB receptor agonist to the A15 increased LH secretion in ovary-intact ewes, suggesting that GABA inhibits A15 neural activity. In ovariectomized anestrous ewes, the same doses of GABA receptor agonist had no effect, but combined administration of a GABAA and GABAB receptor antagonist to the A15 inhibited LH secretion. These data are consistent with the hypothesis that endogenous GABA release within the A15 is low in ovary-intact anestrous ewes and elevated after ovariectomy. Using dual immunocytochemistry, we observed that GABAergic varicosities make close contacts on to A15 neurons and that A15 neurons contain both the GABAA-α1 and the GABAB-R1 receptor subunits. Based on these data, we propose that in anestrous ewes, E2 inhibits release of GABA from afferents to A15 DA neurons, increasing the activity of these DA neurons and thus suppressing episodic secretion of GnRH and LH.

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Activation of Nigral and Pallidal Dopamine D1-Like Receptors Modulates Basal Ganglia Outflow in Monkeys

Journal of Neurophysiology ◽

10.1152/jn.00171.2007 ◽

2007 ◽

Vol 98 (3) ◽

pp. 1489-1500 ◽

Cited By ~ 45

Author(s):

Michele A. Kliem ◽

Nigel T. Maidment ◽

Larry C. Ackerson ◽

Sugong Chen ◽

Yoland Smith ◽

...

Keyword(s):

Basal Ganglia ◽

Rhesus Monkeys ◽

Receptor Agonist ◽

Gaba Release ◽

Aminobutyric Acid ◽

Substantia Nigra Pars Reticulata ◽

Axon Terminals ◽

Discharge Rates ◽

Dopaminergic Tone ◽

Output Neurons

Studies of the effects of dopamine in the basal ganglia have focused on the striatum, whereas the functions of dopamine released in the internal pallidal segment (GPi) or in the substantia nigra pars reticulata (SNr) have received less attention. Anatomic and biochemical investigations have demonstrated the presence of dopamine D1-like receptors (D1LRs) in GPi and SNr, which are primarily located on axons and axon terminals of the GABAergic striatopallidal and striatonigral afferents. Our experiments assessed the effects of D1LR ligands in GPi and SNr on local γ-aminobutyric acid (GABA) levels and neuronal activity in these nuclei in rhesus monkeys. Microinjections of the D1LR receptor agonist SKF82958 into GPi and SNr significantly reduced discharge rates in GPi and SNr, whereas injections of the D1LR antagonist SCH23390 increased firing in the majority of GPi neurons. D1LR activation also increased bursting and oscillations in neuronal discharge in the 3- to 15-Hz band in both structures, whereas D1LR blockade had the opposite effects in GPi. Microdialysis measurements of GABA concentrations in GPi and SNr showed that the D1LR agonist increased the level of the transmitter. Both findings are compatible with the hypothesis that D1LR activation leads to GABA release from striatopallidal or striatonigral afferents, which may secondarily reduce firing of basal ganglia output neurons. The antagonist experiments suggest that a dopaminergic “tone” exists in GPi. Our results support the finding that D1LR activation may have powerful effects on GPi and SNr neurons and may mediate some of the effects of dopamine replacement therapies in Parkinson's disease.

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