Heterogeneity in presynaptic regulation of GABA release from hippocampal inhibitory neurons

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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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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Kainate Acts at Presynaptic Receptors to Increase GABA Release From Hypothalamic Neurons

Journal of Neurophysiology ◽

10.1152/jn.1999.82.2.1059 ◽

1999 ◽

Vol 82 (2) ◽

pp. 1059-1062 ◽

Cited By ~ 28

Author(s):

Qing-Song Liu ◽

Peter R. Patrylo ◽

Xiao-Bing Gao ◽

Anthony N. van den Pol

Keyword(s):

Transmitter Release ◽

Hippocampal Neurons ◽

Gaba Release ◽

Presynaptic Receptors ◽

Inhibitory Neurons ◽

Kainate Receptors ◽

Nmda Receptor Antagonists ◽

Presynaptic Site ◽

Site Of Action ◽

Inhibitory Transmitter

Recent reports suggest that kainate acting at presynaptic receptors reduces the release of the inhibitory transmitter GABA from hippocampal neurons. In contrast, in the hypothalamus in the presence of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d-aspartate (NMDA) receptor antagonists [1-(4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466) and d,l-2-amino-5-phosphonopentanoic acid (AP5)], kainate increased GABA release. In the presence of tetrodotoxin, the frequency, but not the amplitude, of GABA-mediated miniature inhibitory postsynaptic currents (IPSCs) was enhanced by kainate, consistent with a presynaptic site of action. Postsynaptic activation of kainate receptors on cell bodies/dendrites was also found. In contrast to the hippocampus where kainate increases excitability by reducing GABA release, in the hypothalamus where a much higher number of GABAergic cells exist, kainate-mediated activation of transmitter release from inhibitory neurons may reduce the level of neuronal activity in the postsynaptic cell.

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Activation of NPY type 5 receptors induces a long-lasting increase in spontaneous GABA release from cerebellar inhibitory interneurons

Journal of Neurophysiology ◽

10.1152/jn.00755.2011 ◽

2012 ◽

Vol 107 (6) ◽

pp. 1655-1665 ◽

Cited By ~ 12

Author(s):

C. J. Dubois ◽

P. Ramamoorthy ◽

M. D. Whim ◽

S. J. Liu

Keyword(s):

Gaba Release ◽

Long Term Potentiation ◽

Network Activity ◽

Inhibitory Neurons ◽

Inhibitory Interneurons ◽

Membrane Excitability ◽

Inhibitory Transmission ◽

Neuronal Network Activity ◽

Sustained Increase

Neuropeptide Y (NPY), a widely distributed neuropeptide in the central nervous system, can transiently suppress inhibitory synaptic transmission and alter membrane excitability via Y2 and Y1 receptors (Y2rs and Y1rs), respectively. Although many GABAergic neurons express Y5rs, the functional role of these receptors in inhibitory neurons is not known. Here, we investigated whether activation of Y5rs can modulate inhibitory transmission in cerebellar slices. Unexpectedly, application of NPY triggered a long-lasting increase in the frequency of miniature inhibitory postsynaptic currents in stellate cells. NPY also induced a sustained increase in spontaneous GABA release in cultured cerebellar neurons. When cerebellar cultures were examined for Y5r immunoreactivity, the staining colocalized with that of VGAT, a presynaptic marker for GABAergic cells, suggesting that Y5rs are located in the presynaptic terminals of inhibitory neurons. RT-PCR experiments confirmed the presence of Y5r mRNA in the cerebellum. The NPY-induced potentiation of GABA release was blocked by Y5r antagonists and mimicked by application of a selective peptide agonist for Y5r. Thus Y5r activation is necessary and sufficient to trigger an increase in GABA release. Finally, the potentiation of inhibitory transmission could not be reversed by a Y5r antagonist once it was initiated, consistent with the development of a long-term potentiation. These results indicate that activation of presynaptic Y5rs induces a sustained increase in spontaneous GABA release from inhibitory neurons in contrast to the transient suppression of inhibitory transmission that is characteristic of Y1r and Y2r activation. Our findings thus reveal a novel role of presynaptic Y5rs in inhibitory interneurons in regulating GABA release and suggest that these receptors could play a role in shaping neuronal network activity in the cerebellum.

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

Life ◽

10.3390/life11121309 ◽

2021 ◽

Vol 11 (12) ◽

pp. 1309

Author(s):

Valery Petrovich Zinchenko ◽

Artem Mikhailovich Kosenkov ◽

Sergei Gennadevich Gaidin ◽

Alexander Igorevich Sergeev ◽

Ludmila Petrovna Dolgacheva ◽

...

Keyword(s):

Ampa Receptors ◽

Neurotransmitter Release ◽

Domoic Acid ◽

Gaba Release ◽

Gabaergic Neurons ◽

Pivotal Role ◽

Inhibitory Neurons ◽

Glutamatergic Neurons ◽

Selective Agonist ◽

First Time

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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