Properties of GABAergic Neurons Containing Calcium-Permeable Kainate and AMPA-Receptors

Calcium-permeable kainate and AMPA receptors (CP-KARs and CP-AMPARs), as well as NMDARs, play a pivotal role in plasticity and in regulating neurotransmitter release. Here we visualized in the mature hippocampal neuroglial cultures the neurons expressing CP-AMPARs and CP-KARs. These neurons were visualized by a characteristic fast sustained [Ca2+]i increase in response to the agonist of these receptors, domoic acid (DoA), and a selective agonist of GluK1-containing KARs, ATPA. Neurons from both subpopulations are GABAergic. The subpopulation of neurons expressing CP-AMPARs includes a larger percentage of calbindin-positive neurons (39.4 ± 6.0%) than the subpopulation of neurons expressing CP-KARs (14.2 ± 7.5% of CB+ neurons). In addition, we have shown for the first time that NH4Cl-induced depolarization faster induces an [Ca2+]i elevation in GABAergic neurons expressing CP-KARs and CP-AMPARs than in most glutamatergic neurons. CP-AMPARs antagonist, NASPM, increased the amplitude of the DoA-induced Ca2+ response in GABAergic neurons expressing CP-KARs, indicating that neurons expressing CP-AMPARs innervate GABAergic neurons expressing CP-KARs. We assume that CP-KARs in inhibitory neurons are involved in the mechanism of outstripping GABA release upon hyperexcitation.

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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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Participation of Na+ channels in the response of carotid body chemoreceptor cells to hypoxia

AJP Cell Physiology ◽

10.1152/ajpcell.1994.267.3.c738 ◽

1994 ◽

Vol 267 (3) ◽

pp. C738-C744 ◽

Cited By ~ 19

Author(s):

A. Rocher ◽

A. Obeso ◽

M. T. Cachero ◽

B. Herreros ◽

C. Gonzalez

Keyword(s):

Carotid Body ◽

Neurotransmitter Release ◽

Marked Reduction ◽

Adult Rabbit ◽

Na Channels ◽

Na Current ◽

Chemoreceptor Cells ◽

Cell Depolarization ◽

First Time ◽

Mild Hypoxia

The role played by Na+ channels of carotid body (CB) chemoreceptor cells was investigated by studying the effects of tetrodotoxin (TTX) on the release of 3H-labeled catecholamines ([3H]CA) by adult rabbit CBs previously incubated with the precursor [3H]tyrosine. TTX inhibited partially the release of [3H]CA elicited by mild hypoxia (10 or 7% O2) or by depolarizing incubation medium containing 20 or 30 mM KCl, but the response to more intense hypoxia (5 or 2% O2) or to higher KCl concentration (40 or 50 mM) was not significantly affected. The release of [3H]CA elicited by acidic stimuli, either 20% CO2 (pH 6.6) or the protonophore dinitrophenol (100 microM), although comparable in magnitude to that elicited by mild hypoxia, was not modified by TTX. These results provide evidence for the first time that Na+ channels of chemoreceptor cells participate in the transduction of hypoxic stimuli into the neurotransmitter release response of these cells and suggest that Na+ current operates as an amplifying device that enhances the initial cell depolarization mediated by the closure of the O2-sensitive K+ channels. Sympathetic denervation of CBs was followed by a marked reduction in the release of [3H]CA elicited by veratridine or by 20 mM KCl, suggesting that the number of Na+ channels in chemoreceptor cells decreases after denervation.

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Selective Inhibition of Spontaneous But Not Ca2+-Dependent Release Machinery by Presynaptic Group II mGluRs in Rat Cerebellar Slices

Journal of Neurophysiology ◽

10.1152/jn.01282.2005 ◽

2006 ◽

Vol 96 (1) ◽

pp. 86-96 ◽

Cited By ~ 26

Author(s):

Maike Glitsch

Keyword(s):

Action Potential ◽

Glutamate Receptors ◽

Neurotransmitter Release ◽

Metabotropic Glutamate Receptors ◽

Gaba Release ◽

Spontaneous Release ◽

Metabotropic Receptors ◽

Voltage Gated ◽

Metabotropic Glutamate ◽

Group Ii

Two main forms of neurotransmitter release are known: action potential-evoked and spontaneous release. Action potential-evoked release depends on Ca2+entry through voltage-gated Ca2+channels, whereas spontaneous release is thought to be Ca2+-independent. Generally, spontaneous and action potential-evoked release are believed to use the same release machinery to release neurotransmitter. This study shows, using the whole cell patch-clamp technique in rat cerebellar slices, that at the interneuron- Purkinje cell synapse activation of presynaptic group II metabotropic glutamate receptors suppresses spontaneous GABA release through a mechanism independent of voltage-gated Ca2+channels, store-operated Ca2+channels, and Ca2+release from intracellular Ca2+stores, suggesting that the metabotropic receptors target the release machinery directly. Voltage gated Ca2+channel-independent release following increased presynaptic cAMP production is similarly inhibited by these metabotropic receptors. In contrast, both voltage-gated Ca2+channel-dependent and presynaptic N-methyl-d-aspartate receptor-dependent GABA release were unaffected by activation of group II metabotropic glutamate receptors. Hence, the mechanisms underlying spontaneous and Ca2+-dependent GABA release are distinct in that only the former is blocked by group II metabotropic glutamate receptors. Thus the same neurotransmitter, glutamate, can activate or inhibit neurotransmitter release by selecting different receptors that target different release machineries.

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Restoration of Mecp2 expression in GABAergic neurons is sufficient to rescue multiple disease features in a mouse model of Rett syndrome

eLife ◽

10.7554/elife.14198 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 53

Author(s):

Kerstin Ure ◽

Hui Lu ◽

Wei Wang ◽

Aya Ito-Ishida ◽

Zhenyu Wu ◽

...

Keyword(s):

Social Skills ◽

Mouse Model ◽

Rett Syndrome ◽

Therapeutic Option ◽

Neurodevelopmental Disorder ◽

Gabaergic Neurons ◽

Inhibitory Neurons ◽

Extended Lifespan ◽

Inhibitory Signaling

The postnatal neurodevelopmental disorder Rett syndrome, caused by mutations in MECP2, produces a diverse array of symptoms, including loss of language, motor, and social skills and the development of hand stereotypies, anxiety, tremor, ataxia, respiratory dysrhythmias, and seizures. Surprisingly, despite the diversity of these features, we have found that deleting Mecp2 only from GABAergic inhibitory neurons in mice replicates most of this phenotype. Here we show that genetically restoring Mecp2 expression only in GABAergic neurons of male Mecp2 null mice enhanced inhibitory signaling, extended lifespan, and rescued ataxia, apraxia, and social abnormalities but did not rescue tremor or anxiety. Female Mecp2+/- mice showed a less dramatic but still substantial rescue. These findings highlight the critical regulatory role of GABAergic neurons in certain behaviors and suggest that modulating the excitatory/inhibitory balance through GABAergic neurons could prove a viable therapeutic option in Rett syndrome.

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