Adenosine inhibits evoked synaptic transmission primarily by reducing presynaptic calcium influx in area CA1 of hippocampus

Neuron ◽  
1994 ◽  
Vol 12 (5) ◽  
pp. 1139-1148 ◽  
Author(s):  
Ling-Gang Wu ◽  
Peter Saggau
Keyword(s):  
Synaptic Transmission ◽  
Calcium Influx ◽  
Area Ca1 ◽  
Presynaptic Calcium

scholarly journals MCTP is an ER-resident calcium sensor that stabilizes synaptic transmission and homeostatic plasticity

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Özgür Genç ◽  
Dion K Dickman ◽  
Wenpei Ma ◽  
Amy Tong ◽  
Richard D Fetter ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Molecular Mechanisms ◽  
Calcium Influx ◽  
Homeostatic Plasticity ◽  
Calcium Sensor ◽  
C2 Domains ◽  
Calcium Dependent ◽  
Disease Associations ◽  
Transmembrane Regions ◽  
Presynaptic Calcium

Presynaptic homeostatic plasticity (PHP) controls synaptic transmission in organisms from Drosophila to human and is hypothesized to be relevant to the cause of human disease. However, the underlying molecular mechanisms of PHP are just emerging and direct disease associations remain obscure. In a forward genetic screen for mutations that block PHP we identified mctp (Multiple C2 Domain Proteins with Two Transmembrane Regions). Here we show that MCTP localizes to the membranes of the endoplasmic reticulum (ER) that elaborate throughout the soma, dendrites, axon and presynaptic terminal. Then, we demonstrate that MCTP functions downstream of presynaptic calcium influx with separable activities to stabilize baseline transmission, short-term release dynamics and PHP. Notably, PHP specifically requires the calcium coordinating residues in each of the three C2 domains of MCTP. Thus, we propose MCTP as a novel, ER-localized calcium sensor and a source of calcium-dependent feedback for the homeostatic stabilization of neurotransmission.

Hyperthermic Preconditioning of Presynaptic Calcium Regulation in Drosophila

2008 ◽  
Vol 99 (5) ◽  
pp. 2420-2430 ◽  
Author(s):  
M. K. Klose ◽  
H. L. Atwood ◽  
R. M. Robertson
Keyword(s):  
Heat Shock ◽  
Synaptic Transmission ◽  
Motor Neurons ◽  
Neuromuscular Junctions ◽  
Calcium Influx ◽  
Calcium Regulation ◽  
Hsp70 Expression ◽  
Presynaptic Calcium ◽  
Hyperthermic Preconditioning ◽  
The Stability

We examined the thermosensitivity of calcium regulation in Drosophila larval neuromuscular junctions, testing effects of prior heat shock and Hsp70 expression. Motor neurons were loaded with either the ratiometric indicator Fura-dextran or the nonratiometric indicator Oregon Green bis-( o-aminophenoxy)- N,N,N′,N′-tetraacetic acid to monitor parameters of calcium regulation as temperature increased. Nerve terminals treated to a prior heat shock, and those of transgenic flies expressing higher than normal levels of Hsp70, were better able to maintain near-normal resting calcium concentrations, calcium influx, and calcium clearance at higher temperatures. Synaptic transmission was also protected by prior heat shock and by higher than normal Hsp70 expression. Thus the thermal limit of synaptic transmission may be directly linked to the stability of calcium regulation.

Transient reversal of the sodium/calcium exchanger boosts presynaptic calcium and synaptic transmission at a cerebellar synapse

2013 ◽  
Vol 109 (6) ◽  
pp. 1669-1680 ◽  
Author(s):  
Chris J. Roome ◽  
Emmet M. Power ◽  
Ruth M. Empson
Keyword(s):  
Synaptic Transmission ◽  
Information Transfer ◽  
Calcium Influx ◽  
Calcium Entry ◽  
Parallel Fiber ◽  
Sodium Calcium Exchanger ◽  
Reverse Mode ◽  
Sodium Calcium ◽  
Presynaptic Calcium

The sodium/calcium exchanger (NCX) is a widespread transporter that exchanges sodium and calcium ions across excitable membranes. Normally, NCX mainly operates in its “forward” mode, harnessing the electrochemical gradient of sodium ions to expel calcium. During membrane depolarization or elevated internal sodium levels, NCX can instead switch the direction of net flux to expel sodium and allow calcium entry. Such “reverse”-mode NCX operation is frequently implicated during pathological or artificially extended periods of depolarization, not during normal activity. We have used fast calcium imaging, mathematical simulation, and whole cell electrophysiology to study the role of NCX at the parallel fiber-to-Purkinje neuron synapse in the mouse cerebellum. We show that nontraditional, reverse-mode NCX activity boosts the amplitude and duration of parallel fiber calcium transients during short bursts of high-frequency action potentials typical of their behavior in vivo. Simulations, supported by experimental manipulations, showed that accumulation of intracellular sodium drove NCX into reverse mode. This mechanism fueled additional calcium influx into the parallel fibers that promoted synaptic transmission to Purkinje neurons for up to 400 ms after the burst. Thus we provide the first functional demonstration of transient and fast NCX-mediated calcium entry at a major central synapse. This unexpected contribution from reverse-mode NCX appears critical for shaping presynaptic calcium dynamics and transiently boosting synaptic transmission, and is likely to optimize the accuracy of cerebellar information transfer.

Calcium Channels Involved in Synaptic Transmission From Reticulospinal Axons in Lamprey

1999 ◽  
Vol 81 (4) ◽  
pp. 1699-1705 ◽  
Author(s):  
P. Krieger ◽  
A. Büschges ◽  
A. el Manira
Keyword(s):  
Calcium Channels ◽  
Synaptic Transmission ◽  
Calcium Channel ◽  
Calcium Channel Blocker ◽  
Presynaptic Inhibition ◽  
Channel Blocker ◽  
Metabotropic Glutamate Receptor ◽  
Calcium Influx ◽  
Combined Application ◽  
Presynaptic Calcium

Calcium channels involved in synaptic transmission from reticulospinal axons in lamprey. The pharmacology of calcium channels involved in glutamatergic synaptic transmission from reticulospinal axons in the lamprey spinal cord was analyzed with specific agonists and antagonists of different high-voltage activated calcium channels. The N-type calcium channel blocker ω-conotoxin GVIA (ω-CgTx) induced a large decrease of the amplitude of reticulospinal-evoked excitatory postsynaptic potentials (EPSPs). The P/Q-type calcium channel blocker ω-agatoxin IVA (ω-Aga) also reduced the amplitude of the reticulospinal EPSPs, but to a lesser extent than ω-CgTx. The dihydropyridine agonist Bay K and antagonist nimodipine had no effect on the amplitude of the reticulospinal EPSP. Combined application of ω-CgTx and ω-Aga strongly decreased the amplitude the EPSPs but was never able to completely block them, indicating that calcium channels insensitive to these toxins (R-type) are also involved in synaptic transmission from reticulospinal axons. We have previously shown that the group III metabotropic glutamate receptor agonistl(+)-2-amino-4-phosphonobutyric acid (l-AP4) mediates presynaptic inhibition at the reticulospinal synapse. To test if this presynaptic effect is mediated through inhibition of calcium influx, the effect of l-AP4 on reticulospinal transmission was tested before and after blockade of N-type channels, which contribute predominantly to transmitter release at this synapse. Blocking the N-type channels with ω-CgTx did not prevent inhibition of reticulospinal synaptic transmission by l-AP4. In addition, l-AP4 had no affect on the calcium current recorded in the somata of reticulospinal neurons or on the calcium component of action potentials in reticulospinal axons. These results show that synaptic transmission from reticulospinal axons in the lamprey is mediated by calcium influx through N-, P/Q- and R-type channels, with N-type channels playing the major role. Furthermore, presynaptic inhibition of reticulospinal transmission byl-AP4 appears not to be mediated through inhibition of presynaptic calcium channels.

Growth Hormone Enhances Excitatory Synaptic Transmission in Area CA1 of Rat Hippocampus

2006 ◽  
Vol 95 (5) ◽  
pp. 2962-2974 ◽  
Author(s):  
Ghada S. Mahmoud ◽  
Lawrence M. Grover
Keyword(s):  
Growth Hormone ◽  
Synaptic Transmission ◽  
Pi3 Kinase ◽  
Janus Kinase ◽  
Excitatory Synaptic Transmission ◽  
Common Mechanism ◽  
Hippocampal Function ◽  
Short Term ◽  
Area Ca1 ◽  
Short Term Effects

The hippocampus produces growth hormone (GH) and contains GH receptors, suggesting a potential role for GH signaling in the regulation of hippocampal function. In agreement with this possibility, previous investigations have found altered hippocampal function and hippocampal-dependent learning and memory after chronic GH administration or deficiency. In this study we applied GH to in vitro rat hippocampal brain slices, to determine whether GH has short-term effects on hippocampal function in addition to previously documented chronic effects. We found that GH enhanced both AMPA- and NMDA-receptor–mediated excitatory postsynaptic potentials (EPSPs) in hippocampal area CA1, but did not alter GABAA-receptor–mediated inhibitory synaptic transmission. GH enhancement of excitatory synaptic transmission was gradual, requiring 60–70 min to reach maximum, and occurred without any change in paired-pulse facilitation, suggesting a possible postsynaptic site of action. In CA1 pyramidal neurons, GH enhancement of EPSPs was correlated with significant hyperpolarization and decreased input resistance. GH enhancement of EPSPs required Janus kinase 2 (JAK2), phosphatidylinositol-3 (PI3) kinase, mitogen-activated protein (MAP) kinase kinase (MEK), and synthesis of new proteins. Although PI3 kinase and MEK were required for initiation of GH effects on excitatory synaptic transmission, they were not required for maintained enhancement of EPSPs. GH treatment and tetanus-induced long-term potentiation were mutually occluding, suggesting a common mechanism or mechanisms in both forms of synaptic enhancement. Our results demonstrate that GH has powerful short-term effects on hippocampal function, and extend the timescale for potential roles of GH in regulating hippocampal function and hippocampal-dependent behaviors.

scholarly journals Homeostatic synaptic depression is achieved through a regulated decrease in presynaptic calcium channel abundance

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Michael A Gaviño ◽  
Kevin J Ford ◽  
Santiago Archila ◽  
Graeme W Davis
Keyword(s):  
Synaptic Plasticity ◽  
Neuromuscular Junction ◽  
Action Potential ◽  
Calcium Channel ◽  
Neurotransmitter Release ◽  
Calcium Influx ◽  
Homeostatic Synaptic Plasticity ◽  
Action Potential Waveform ◽  
Presynaptic Calcium ◽  
Potential Waveform

Homeostatic signaling stabilizes synaptic transmission at the neuromuscular junction (NMJ) of Drosophila, mice, and human. It is believed that homeostatic signaling at the NMJ is bi-directional and considerable progress has been made identifying mechanisms underlying the homeostatic potentiation of neurotransmitter release. However, very little is understood mechanistically about the opposing process, homeostatic depression, and how bi-directional plasticity is achieved. Here, we show that homeostatic potentiation and depression can be simultaneously induced, demonstrating true bi-directional plasticity. Next, we show that mutations that block homeostatic potentiation do not alter homeostatic depression, demonstrating that these are genetically separable processes. Finally, we show that homeostatic depression is achieved by decreased presynaptic calcium channel abundance and calcium influx, changes that are independent of the presynaptic action potential waveform. Thus, we identify a novel mechanism of homeostatic synaptic plasticity and propose a model that can account for the observed bi-directional, homeostatic control of presynaptic neurotransmitter release.

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