scholarly journals SYMPOSIUM REPORT. Background synaptic activity in rat entorhinal cortical neurones: differential control of transmitter release by presynaptic receptors

2004 ◽  
Vol 562 (1) ◽  
pp. 107-120 ◽  
Author(s):  
Roland S. G. Jones ◽  
Gavin L. Woodhall
Keyword(s):  
Transmitter Release ◽  
Presynaptic Receptors ◽  
Synaptic Activity ◽  
Symposium Report ◽  
Differential Control

Influence of presynaptic receptors on neuromuscular transmission in rat

1982 ◽  
Vol 242 (5) ◽  
pp. C366-C372 ◽  
Author(s):  
D. F. Wilson
Keyword(s):  
Transmitter Release ◽  
Action Potentials ◽  
Physiological Function ◽  
Motor Nerve ◽  
Presynaptic Receptors ◽  
End Plate ◽  
Feedback Pathway ◽  
Partial Blockade ◽  
Ach Receptors

The presence and physiological significance of acetylcholine (ACh) receptors on motor nerve terminals was examined at the rat diaphragm neuromuscular junction. Intracellular recording techniques were used to monitor end-plate potentials (EPP), miniature end-plate potentials (MEPP), and resting potentials of the muscle fibers. Muscle action potentials were blocked by the cut-muscle technique. Quantal release was determined by the ratio EPP/MEPP, after correcting for nonlinear summation. Blockade of acetylcholinesterase with eserine and neostigmine was tested to determine the influence of residual ACh on transmitter release. Partial blockade of ACh receptors with curare was examined to further clarify the role of these presynaptic receptors. The experiments demonstrate that residual ACh inhibits transmitter release and that blockade of ACh receptors enhances transmitter release. It is concluded that presynaptic ACh receptors exist and that they serve an important physiological function. It is suggested that the presynaptic ACh receptors normally serve to limit transmitter release in a negative feedback pathway.

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.

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.

Impulse activity of a crayfish motoneuron regulated its neuromuscular synaptic properties

1989 ◽  
Vol 61 (1) ◽  
pp. 91-96 ◽  
Author(s):  
G. A. Lnenicka ◽  
H. L. Atwood
Keyword(s):  
Muscle Activity ◽  
Transmitter Release ◽  
Impulse Activity ◽  
Peripheral Region ◽  
Synaptic Activity ◽  
Synaptic Physiology ◽  
Neuromuscular Synapses ◽  
Long Term Changes

1. Previous studies have demonstrated that initial transmitter release, fatigability, and the morphology of identified crayfish neuromuscular synapses adapt to long-term changes in motoneuron impulse activity. 2. Experiments were performed to determine whether these long-term, adaptive alterations in neuromuscular synaptic physiology are triggered by changes in neuromuscular synaptic activity, muscle activity, or neuronal impulse activity. The fast closer excitor of the crayfish claw, a phasic motoneuron, was studied. Either the central or the peripheral region of the motoneuron was selectively stimulated in vivo by blocking impulse activity midway along the motor axon with localized application of tetrodotoxin and stimulating either central or distal to the blocked region. 3. Neither muscle activity nor transmitter release from the neuromuscular synapses was required to trigger the changes in synaptic physiology. Stimulation central to the block induced changes in neuromuscular transmission that included a long-lasting decrease in initial transmitter release and increased fatique resistance. 4. Because peripheral stimulation also produced decreased initial transmitter release, it appears that increased impulse activity in either region of the motoneuron can produce the synaptic changes. These results along with earlier findings suggest that neuronal depolarization induces adaptive, long-term changes in synapses. 5. These results are discussed in relation to findings at vertebrate and invertebrate synapses.

Analysis of repolarization of presynaptic motor terminals in Drosophila larvae using potassium-channel-blocking drugs and mutations

1992 ◽  
Vol 170 (1) ◽  
pp. 93-111
Author(s):  
M. Gho ◽  
B. Ganetzky
Keyword(s):  
Transmitter Release ◽  
Neuronal Cell ◽  
Potassium Currents ◽  
Ionic Currents ◽  
Major Effect ◽  
Synaptic Activity ◽  
Synaptic Currents ◽  
Presynaptic Terminals ◽  
Neuronal Cell Bodies ◽  
Drosophila Larvae

In Drosophila melanogaster muscles and neuronal cell bodies at least four different potassium currents have been identified whose activity shapes the electrical properties of these cells. Potassium currents also control repolarization of presynaptic terminals and, therefore, exert a major effect on transmitter release and synaptic plasticity. However, because of the small size of presynaptic terminals in Drosophila, it has not been possible to analyze the potassium currents they express. As a first approach to characterizing the ionic currents present at presynaptic motor terminals of Drosophila larvae, we recorded synaptic currents at the neuromuscular junction. From the alterations in evoked synaptic currents caused by various drugs and by mutations known to affect potassium currents in other tissues, we suggest that the repolarizing mechanism in presynaptic terminals consists of at least four distinct currents. One is affected by aminopyridines or Sh mutations, a second component is affected by the slo mutation, a third is sensitive to quinidine and one or more additional components are blocked by tetraethylammonium. Depolarization depends on a presynaptic calcium current, which displays only slight voltage-dependent inactivation. Because the mechanism of repolarization exerts a major effect on synaptic activity, this analysis provides a framework for further genetic and molecular dissection of the basic processes involved in the regulation of transmitter release.

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 Dynamic Modulation of Phasic and Asynchronous Glutamate Release in Hippocampal Synapses

2010 ◽  
Vol 103 (1) ◽  
pp. 392-401 ◽  
Author(s):  
Chun Yun Chang ◽  
Steven Mennerick
Keyword(s):  
Action Potential ◽  
Transmitter Release ◽  
Hippocampal Neurons ◽  
Glutamate Release ◽  
Inhibitory Effects ◽  
Vesicle Release ◽  
Hippocampal Synapses ◽  
Asynchronous Release ◽  
Independent Effects ◽  
Differential Control

Although frequency-dependent short-term presynaptic plasticity has been of long-standing interest, most studies have emphasized modulation of the synchronous, phasic component of transmitter release, most evident with a single or a few presynaptic stimuli. Asynchronous transmitter release, vesicle fusion not closely time locked to presynaptic action potentials, can also be prominent under certain conditions, including repetitive stimulation. Asynchrony has often been attributed to residual Ca2+ buildup in the presynaptic terminal. We verified that a number of manipulations of Ca2+ handling and influx selectively alter asynchronous release relative to phasic transmitter release during action potential trains in cultured excitatory autaptic hippocampal neurons. To determine whether other manipulations of vesicle release probability also selectively modulate asynchrony, we probed the actions of one thoroughly studied modulator class whose actions on phasic versus asynchronous release have not been investigated. We examined the effects of the phorbol ester PDBu, which has protein kinase C (PKC) dependent and independent actions on presynaptic transmitter release. PDBu increased phasic and asynchronous release in parallel. However, while PKC inhibition had relatively minor inhibitory effects on PDBu potentiation of phasic and total release during action potential trains, PKC inhibition strongly reduced phorbol-potentiated asynchrony, through actions most evident late during stimulus trains. These results lend new insight into PKC-dependent and -independent effects on transmitter release and suggest the possibility of differential control of synchronous versus asynchronous vesicle release.

Evidence that transmitter release in sympathetic nerves is not set by feedback via presynaptic receptors

1983 ◽  
Vol 61 (10) ◽  
pp. 1197-1201 ◽  
Author(s):  
Stanley Kalsner
Keyword(s):  
Guinea Pig ◽  
Negative Feedback ◽  
Noradrenaline Release ◽  
Transmitter Release ◽  
Feedback Regulation ◽  
Feedback System ◽  
Sympathetic Nerves ◽  
Presynaptic Receptors ◽  
Negative Feedback Regulation

The possibility of negative feedback regulation of noradrenaline release was studied in the sympathetically innervated ureters of the guinea pig mounted in vitro. Tissues were transmurally stimulated with 300 pulses at 2 Hz over a range of voltages, from 10 to 60 V. It was determined that the output of transmitter increased with increasing voltage but that the effects of supposed presynaptic antagonism by yohimbine and presynaptic agonism by added noradrenaline did not fulfill the requirements of presynaptic theory governing negative feedback. It is concluded that the presynaptic effects of these drugs is neither linked to the operation of a negative feedback system nor sensitive to the perineuronal concentrations of free and active neurotransmitter.

scholarly journals Aberrant Morphology and Residual Transmitter Release at the Munc13-Deficient Mouse Neuromuscular Synapse

2005 ◽  
Vol 25 (14) ◽  
pp. 5973-5984 ◽  
Author(s):  
Frédérique Varoqueaux ◽  
Michèle S. Sons ◽  
Jaap J. Plomp ◽  
Nils Brose
Keyword(s):  
Neuromuscular Junction ◽  
Synaptic Vesicle ◽  
Motor Neurons ◽  
Transmitter Release ◽  
Hippocampal Neurons ◽  
Neuromuscular Junctions ◽  
Neuromuscular Synapse ◽  
Synaptic Activity ◽  
Neuromuscular Synaptogenesis ◽  
Deficient Mice

ABSTRACT In cultured hippocampal neurons, synaptogenesis is largely independent of synaptic transmission, while several accounts in the literature indicate that synaptogenesis at cholinergic neuromuscular junctions in mammals appears to partially depend on synaptic activity. To systematically examine the role of synaptic activity in synaptogenesis at the neuromuscular junction, we investigated neuromuscular synaptogenesis and neurotransmitter release of mice lacking all synaptic vesicle priming proteins of the Munc13 family. Munc13-deficient mice are completely paralyzed at birth and die immediately, but form specialized neuromuscular endplates that display typical synaptic features. However, the distribution, number, size, and shape of these synapses, as well as the number of motor neurons they originate from and the maturation state of muscle cells, are profoundly altered. Surprisingly, Munc13-deficient synapses exhibit significantly increased spontaneous quantal acetylcholine release, although fewer fusion-competent synaptic vesicles are present and nerve stimulation-evoked secretion is hardly elicitable and strongly reduced in magnitude. We conclude that the residual transmitter release in Munc13-deficient mice is not sufficient to sustain normal synaptogenesis at the neuromuscular junction, essentially causing morphological aberrations that are also seen upon total blockade of neuromuscular transmission in other genetic models. Our data confirm the importance of Munc13 proteins in synaptic vesicle priming at the neuromuscular junction but indicate also that priming at this synapse may differ from priming at glutamatergic and γ-aminobutyric acid-ergic synapses and is partly Munc13 independent. Thus, non-Munc13 priming proteins exist at this synapse or vesicle priming occurs in part spontaneously: i.e., without dedicated priming proteins in the release machinery.

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