Enhancement of Synaptic Excitation by GABAA Receptor Antagonists in Rat Embryonic Midbrain Culture

1998 ◽  
Vol 79 (2) ◽  
pp. 1113-1116 ◽  
Author(s):  
Jutta Rohrbacher ◽  
Katja Sauer ◽  
Andrea Lewen ◽  
Ulrich Misgeld
Keyword(s):  
Transmitter Release ◽  
Glutamate Release ◽  
Synaptic Activity ◽  
Aminobutyric Acid ◽  
Receptor Antagonists ◽  
Synaptic Excitation ◽  
Aspartate Receptor ◽  
Cell Recording ◽  
Per Se ◽  
Excitatory Drive

Rohrbacher, Jutta, Katja Sauer, Andrea Lewen, and Ulrich Misgeld. Enhancement of synaptic excitation by GABAA receptor antagonists in rat embryonic midbrain culture. J. Neurophysiol. 79: 1113–1116, 1998. Alterations of synaptic excitation induced by exposure to γ-aminobutyric acid-A (GABAA) receptor antagonists were investigated employing tight-seal whole cell recording from single neurons or pairs of neurons in rat embryonic midbrain culture. Application of GABAA receptor antagonists led to sustained depolarizations followed by synchronous paroxysmal depolarization shifts (PDSs). PDSs induced a transient increase in miniature excitatory postsynaptic currents in the presence as well as in the absence of a N-methyl-d-aspartate receptor antagonist. The increase in glutamate release supports the excitatory drive required to reinitiate PDSs from the quiescent interburst intervals. After washout of GABAA receptor antagonists, synaptic activity remained grouped, regardless of the presence or absence of PDS blockade by tetrodotoxin (TTX). Impediment of action potential-triggered transmitter release by Cd2+ or TTX also induced grouped activity. We conclude that changes in synaptic excitation are produced by the impaired GABAA inhibition per se and by the initiation of PDSs.

scholarly journals Circuit contributions to sensory-driven glutamatergic drive of olfactory bulb mitral and tufted cells during odorant inhalation

2021 ◽  
Author(s):  
Andrew K. Moran ◽  
Thomas P. Eiting ◽  
Matt Wachowiak
Keyword(s):  
Olfactory Bulb ◽  
Gabab Receptor ◽  
Glutamate Release ◽  
Excitatory Input ◽  
Slight Reduction ◽  
Receptor Antagonists ◽  
Glutamate Signaling ◽  
Inhibitory Circuits ◽  
Primary Determinant ◽  
Excitatory Drive

In the mammalian olfactory bulb (OB), mitral/tufted (MT) cells respond to odorant inhalation with diverse temporal patterns that are thought to encode odor information. Much of this diversity is already apparent at the level of glutamatergic input to MT cells, which receive direct, monosynaptic excitatory input from olfactory sensory neurons (OSNs) as well as multisynaptic excitatory drive via glutamatergic interneurons. Both pathways are also subject to modulation by inhibitory circuits in the glomerular layer of the OB. To understand the role of direct OSN input versus postsynaptic OB circuit mechanisms in shaping diverse dynamics of glutamatergic drive to MT cells, we imaged glutamate signaling onto MT cell dendrites in anesthetized mice while blocking multisynaptic excitatory drive with ionotropic glutamate receptor antagonists and blocking presynaptic modulation of glutamate release from OSNs with GABAB receptor antagonists. GABAB receptor blockade increased the magnitude of inhalation-linked glutamate transients onto MT cell apical dendrites without altering their inhalation-linked dynamics, confirming that presynaptic inhibition impacts the gain of OSN inputs to the OB. Surprisingly, blockade of multisynaptic excitation only modestly impacted glutamatergic input to MT cells, causing a slight reduction in the amplitude of inhalation-linked glutamate transients in response to low odorant concentrations and no change in the dynamics of each transient. Postsynaptic blockade also modestly impacted glutamate dynamics over a slower timescale, mainly by reducing adaptation of the glutamate response across multiple inhalations of odorant. These results suggest that direct glutamatergic input from OSNs provides the bulk of excitatory drive to MT cells, and that diversity in the dynamics of this input may be a primary determinant of the temporal diversity in MT cell responses that underlies odor representations at this stage.

Relative magnitude of tonic and phasic synaptic excitation of medullary inspiratory neurons in dogs

2000 ◽  
Vol 279 (2) ◽  
pp. R639-R649 ◽  
Author(s):  
M. Krolo ◽  
E. A. Stuth ◽  
M. Tonkovic-Capin ◽  
F. A. Hopp ◽  
D. R. McCrimmon ◽  
...  
Keyword(s):  
Nmda Receptors ◽  
Late Onset ◽  
Relative Magnitude ◽  
Cholinergic Receptors ◽  
Aminobutyric Acid ◽  
Tonic Activity ◽  
Synaptic Excitation ◽  
Relative Contribution ◽  
Discharge Patterns ◽  
Excitatory Drive

The relative contribution of phasic and tonic excitatory synaptic drives to the augmenting discharge patterns of inspiratory (I) neurons within the ventral respiratory group (VRG) was studied in anesthetized, ventilated, paralyzed, and vagotomized dogs. Multibarrel micropipettes were used to record simultaneously single-unit neuronal activity and pressure microejected antagonists of GABAergic, glycinergic, N-methyl-d-aspartate (NMDA) and non-NMDA glutamatergic, and cholinergic receptors. The discharge patterns were quantified via cycle-trigger histograms. The findings suggest that two-thirds of the excitatory drive to caudal VRG I neurons is tonic and mediated by NMDA receptors and the other third is ramp-like phasic and mediated by non-NMDA receptors. Cholinergic receptors do not appear to be involved. The silent expiratory phase is produced by phasic inhibition of the tonic activity, and ≈80% of this inhibition is mediated by γ-aminobutyric acid receptors (GABAA) and ≈20% by glycine receptors. Phasic I inhibition by the I decrementing neurons does not appear to contribute to the predominantly step-ramp patterns of these I neurons. However, this decrementing inhibition may be very prominent in controlling the rate of augmentation in late-onset I neurons and those with ramp patterns lacking the step component.

scholarly journals Synaptic excitation is regulated by the postsynaptic dSK channel at the Drosophila larval NMJ

2014 ◽  
Vol 111 (12) ◽  
pp. 2533-2543 ◽  
Author(s):  
Daniel M. Gertner ◽  
Sunil Desai ◽  
Gregory A. Lnenicka
Keyword(s):  
Transmitter Release ◽  
Membrane Conductance ◽  
Postsynaptic Membrane ◽  
Synaptic Activity ◽  
Muscle Membrane ◽  
Resting Membrane Potential ◽  
Excitatory Postsynaptic Potential ◽  
Synaptic Excitation ◽  
Sk Channel ◽  
Larval Neuromuscular Junction

In the mammalian central nervous system, the postsynaptic small-conductance Ca2+-dependent K+ (SK) channel has been shown to reduce postsynaptic depolarization and limit Ca2+ influx through N-methyl-d-aspartate receptors. To examine further the role of the postsynaptic SK channel in synaptic transmission, we studied its action at the Drosophila larval neuromuscular junction (NMJ). Repetitive synaptic stimulation produced an increase in postsynaptic membrane conductance leading to depression of excitatory postsynaptic potential amplitude and hyperpolarization of the resting membrane potential (RMP). This reduction in synaptic excitation was due to the postsynaptic Drosophila SK (dSK) channel; synaptic depression, increased membrane conductance and RMP hyperpolarization were reduced in dSK mutants or after expressing a Ca2+ buffer in the muscle. Ca2+ entering at the postsynaptic membrane was sufficient to activate dSK channels based upon studies in which the muscle membrane was voltage clamped to prevent opening voltage-dependent Ca2+ channels. Increasing external Ca2+ produced an increase in resting membrane conductance and RMP that was not seen in dSK mutants or after adding the glutamate-receptor blocker philanthotoxin. Thus it appeared that dSK channels were also activated by spontaneous transmitter release and played a role in setting membrane conductance and RMP. In mammals, dephosphorylation by protein phosphatase 2A (PP2A) increased the Ca2+ sensitivity of the SK channel; PP2A appeared to increase the sensitivity of the dSK channel since PP2A inhibitors reduced activation of the dSK channel by evoked synaptic activity or increased external Ca2+. It is proposed that spontaneous and evoked transmitter release activate the postsynaptic dSK channel to limit synaptic excitation and stabilize synapses.

scholarly journals Gamma-Aminobutyric Acid Modulates Local Brain Oxygen Consumption and Blood Flow in Rat Cerebellar Cortex

2007 ◽  
Vol 28 (5) ◽  
pp. 906-915 ◽  
Author(s):  
Kirsten Caesar ◽  
Nikolas Offenhauser ◽  
Martin Lauritzen
Keyword(s):  
Blood Flow ◽  
Oxygen Consumption ◽  
Metabolic Rate ◽  
Climbing Fiber ◽  
Synaptic Activity ◽  
Aminobutyric Acid ◽  
Control Mechanisms ◽  
Gamma Aminobutyric Acid ◽  
Synaptic Excitation ◽  
Fiber Stimulation

In the awake brain, the global metabolic rate of oxygen consumption is largely constant, while variations exist between regions dependent on the ongoing activity. This suggests that control mechanisms related to activity, that is, neuronal signaling, may redistribute metabolism in favor of active networks. This study examined the influence of γ-aminobutyric acid (GABA) tone on local increases in cerebellar metabolic rate of oxygen (CeMRO2) evoked by stimulation of the excitatory, glutamatergic climbing fiber-Purkinje cell synapse in rat cerebellum. In this network, the postsynaptic depolarization produced by synaptic excitation is preserved despite variations in GABAergic tone. Climbing fiber stimulation induced frequency-dependent increases in synaptic activity and CeMRO2 under control conditions. Topical application of the GABAA receptor agonist muscimol blocked the increase in CeMRO2 evoked by synaptic excitation concomitant with attenuation of cerebellar blood flow (CeBF) responses. The effect was reversed by the GABAA receptor antagonist bicuculline, which also reversed the effect of muscimol on synaptic activity and CeBF. Climbing fiber stimulation during bicuculline application alone produced a delayed undershoot in CeBF concomitant with a prolonged rise in CeMRO2. The findings are consistent with the hypothesis that activity-dependent rises in CeBF and CeMRO2 are controlled by a common feed-forward pathway and provide evidence for modification of cerebral blood flow and CMRO2 by GABA.

Characterization of postsynaptic Ca2+ signals at the Drosophila larval NMJ

2011 ◽  
Vol 106 (2) ◽  
pp. 710-721 ◽  
Author(s):  
Sunil A. Desai ◽  
Gregory A. Lnenicka
Keyword(s):  
Transmitter Release ◽  
Postsynaptic Membrane ◽  
Synaptic Activity ◽  
Synaptic Efficacy ◽  
Single Action ◽  
Synaptic Homeostasis ◽  
Multiple Transcripts ◽  
Quantal Size ◽  
Intracellular Ca ◽  
Larval Neuromuscular Junction

Postsynaptic intracellular Ca2+ concentration ([Ca2+]i) has been proposed to play an important role in both synaptic plasticity and synaptic homeostasis. In particular, postsynaptic Ca2+ signals can alter synaptic efficacy by influencing transmitter release, receptor sensitivity, and protein synthesis. We examined the postsynaptic Ca2+ transients at the Drosophila larval neuromuscular junction (NMJ) by injecting the muscle fibers with Ca2+ indicators rhod-2 and Oregon Green BAPTA-1 (OGB-1) and then monitoring their increased fluorescence during synaptic activity. We observed discrete postsynaptic Ca2+ transients along the NMJ during single action potentials (APs) and quantal Ca2+ transients produced by spontaneous transmitter release. Most of the evoked Ca2+ transients resulted from the release of one or two quanta of transmitter and occurred largely at synaptic boutons. The magnitude of the Ca2+ signals was correlated with synaptic efficacy; the Is terminals, which produce larger excitatory postsynaptic potentials (EPSPs) and have a greater quantal size than Ib terminals, produced a larger Ca2+ signal per terminal length and larger quantal Ca2+ signals than the Ib terminals. During a train of APs, the postsynaptic Ca2+ signal increased but remained localized to the postsynaptic membrane. In addition, we showed that the plasma membrane Ca2+-ATPase (PMCA) played a role in extruding Ca2+ from the postsynaptic region of the muscle. Drosophila melanogaster has a single PMCA gene, predicted to give rise to various isoforms by alternative splicing. Using RT-PCR, we detected the expression of multiple transcripts in muscle and nervous tissues; the physiological significance of the same is yet to be determined.

Altered desensitization produces enhancement of EPSPs in neocortical neurons

1994 ◽  
Vol 72 (2) ◽  
pp. 1032-1036 ◽  
Author(s):  
M. R. Pelletier ◽  
J. J. Hablitz
Keyword(s):  
Nmda Receptors ◽  
Time Course ◽  
Glutamate Release ◽  
Epileptiform Activity ◽  
Brain Slices ◽  
Synaptic Activity ◽  
Membrane Properties ◽  
Repetitive Firing ◽  
Resting Membrane Potential ◽  
Bath Application

1. Neocortical brain slices were prepared from rats (35–50 days of age) and maintained in vitro. Intracellular recordings were obtained from neurons in cortical layers II/III. The effect of bath application of cyclothiazide (CYZ), a potent blocker of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor desensitization, on evoked synaptic activity and passive membrane properties was investigated. 2. Bath application of CYZ did not significantly affect resting membrane potential, input resistance, or repetitive firing. CYZ increased both the amplitude and duration of evoked excitatory postsynaptic potentials (EPSPs). Polysynaptic responses were also augumented. These effects persisted after the blockade of N-methyl-D-aspartate (NMDA) receptors with D-2-amino-5-phosphonovaleric acid (D-APV). The magnitude of these effects appeared to vary directly with stimulation intensity and presumably, amount of glutamate release. 3. Epileptiform activity was induced by bath application of bicuculline methiodide. The amplitude and duration of evoked paroxysmal discharges were increased by CYZ. Similar results were seen in presence of D-APV. 4. These results indicate that CYZ has significant effects on synaptic transmission. Desensitization of non-NMDA receptors may be an important mechanism for determining the time course of EPSPs and in curtailing epileptiform responses in the rat neocortex.

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