Ca
            <sup>2+</sup>
            stores and use-dependent facilitation of presynaptic Ca
            <sup>2+</sup>
            signaling

Scott, Ricardo; Rusakov, Dmitri A.

doi:10.1073/pnas.0808119105

Cited by 6 publications

(3 citation statements)

References 4 publications

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“…Internal stores might contribute to Ca 2+ transients (Cochilla and Alford, 1998; Emptage et al, 2001; Scott and Rusakov, 2008). Calculations of Ca 2+ entering, and κ end will be distorted if secondary Ca 2+ sources exist.…”

Section: Resultsmentioning

confidence: 99%

Quantitation and Simulation of Single Action Potential-Evoked Ca²⁺Signals in CA1 Pyramidal Neuron Presynaptic Terminals

Hamid

Church

Alford

2019

eNeuro

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Presynaptic Ca2+ evokes exocytosis, endocytosis, and synaptic plasticity. However, Ca2+ flux and interactions at presynaptic molecular targets are difficult to quantify because fluorescence imaging has limited resolution. In rats of either sex, we measured single varicosity presynaptic Ca2+ using Ca2+ dyes as buffers, and constructed models of Ca2+ dispersal. Action potentials evoked Ca2+ transients with little variation when measured with low-affinity dye (peak amplitude 789 ± 39 nM, within 2 ms of stimulation; decay times, 119 ± 10 ms). Endogenous Ca2+ buffering capacity, action potential-evoked free [Ca2+]i, and total Ca2+ amounts entering terminals were determined using Ca2+ dyes as buffers. These data constrained Monte Carlo (MCell) simulations of Ca2+ entry, buffering, and removal. Simulations of experimentally-determined Ca2+ fluxes, buffered by simulated calbindin28K well fit data, and were consistent with clustered Ca2+ entry followed within 4 ms by diffusion throughout the varicosity. Repetitive stimulation caused free varicosity Ca2+ to sum. However, simulated in nanometer domains, its removal by pumps and buffering was negligible, while local diffusion dominated. Thus, Ca2+ within tens of nanometers of entry, did not accumulate. A model of synaptotagmin1 (syt1)-Ca2+ binding indicates that even with 10 µM free varicosity evoked Ca2+, syt1 must be within tens of nanometers of channels to ensure occupation of all its Ca2+-binding sites. Repetitive stimulation, evoking short-term synaptic enhancement, does not modify probabilities of Ca2+ fully occupying syt1’s C2 domains, suggesting that enhancement is not mediated by Ca2+-syt1 interactions. We conclude that at spatiotemporal scales of fusion machines, Ca2+ necessary for their activation is diffusion dominated.

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Section: Resultsmentioning

confidence: 99%

Quantitation and Simulation of Single Action Potential-Evoked Ca²⁺Signals in CA1 Pyramidal Neuron Presynaptic Terminals

Hamid

Church

Alford

2019

eNeuro

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“…Large mossy fiber varicosities can be visualized in living slices with two-photon excitation fluorescence imaging integrated with patch-clamp electrophysiology (Scott and Rusakov, 2006, 2008; Nistico et al, 2012). Granule cell loading with a morphological tracer such as Alexa Fluor 594 (20–40 μM), together with a high-affinity Ca 2+ indicator, Fluo-4 (200 μM), or Oregon Green BAPTA-1 (200 μM), then potentially allows Ca 2+ signaling in unambiguously identified mossy fiber boutons.…”

Section: Methods Available To Investigate Presynaptic Receptor Functionmentioning

confidence: 99%

Ionotropic receptors at hippocampal mossy fibers: roles in axonal excitability, synaptic transmission, and plasticity

Ruiz¹,

Kullmann²

2013

Front. Neural Circuits

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Dentate granule cells process information from the enthorinal cortex en route to the hippocampus proper. These neurons have a very negative resting membrane potential and are relatively silent in the slice preparation. They are also subject to strong feed-forward inhibition. Their unmyelinated axon or mossy fiber ramifies extensively in the hilus and projects to stratum lucidum where it makes giant en-passant boutons with CA3 pyramidal neurons. There is compelling evidence that mossy fiber boutons express presynaptic GABAA receptors, which are commonly found in granule cell dendrites. There is also suggestive evidence for the presence of other ionotropic receptors, including glycine, NMDA, and kainate receptors, in mossy fiber boutons. These presynaptic receptors have been proposed to lead to mossy fiber membrane depolarization. How this phenomenon alters the excitability of synaptic boutons, the shape of presynaptic action potentials, Ca2+ influx and neurotransmitter release has remained elusive, but high-resolution live imaging of individual varicosities and direct patch-clamp recordings have begun to shed light on these phenomena. Presynaptic GABAA and kainate receptors have also been reported to facilitate the induction of long-term potentiation at mossy fiber—CA3 synapses. Although mossy fibers are highly specialized, some of the principles emerging at this connection may apply elsewhere in the CNS.

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“…Internal stores might contribute to Ca 2+ transients (Cochilla and Alford, 1998;Emptage et al, 2001;Scott and Rusakov, 2008). Calculations of Ca 2+ entering, and kend will be distorted if secondary Ca 2+ sources exist.…”

Section: Ca 2+ Source and Removal From The Terminalmentioning

confidence: 99%

Quantitation of single action potential-evoked Ca²⁺signals in CA1 pyramidal neuron presynaptic terminals

Church

Hamid

Alford

2018

Preprint

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Presynaptic Ca 2+ evokes exocytosis, endocytosis, and short-term synaptic plasticity. However, Ca 2+ flux and interactions at presynaptic molecular targets are difficult to determine, because imaging has limited resolution. We measured single varicosity presynaptic Ca 2+ using Ca 2+ dyes as buffers, and constructed models of Ca 2+ dispersal. Action potentials evoked Ca 2+ transients (peak amplitude, 789±39 nM, within 2 ms of stimulation; decay times, 119±10 ms) with little variation when measured with low-affinity dye. Endogenous Ca 2+ buffering capacities, action potential-evoked free [Ca 2+ ]i and total amounts entering terminals were determined using highaffinity Ca 2+ dyes to buffer Ca 2+ transients. These data constrained Monte Carlo (MCell) simulations of Ca 2+ entry, buffering, and removal. Data were well-fit with simulations of experimentally-determined Ca 2+ fluxes, buffered by simulated Calbindin28K. Simulations were consistent with clustered Ca 2+ entry followed within 2 ms by diffusion throughout the varicosity.Repetitive stimulation caused free varicosity Ca 2+ to sum. However, simulated in nanometer domains, its removal by pumps and buffering was negligible, while diffusion rates were high.Thus, Ca 2+ within tens of nanometers of entry, did not accumulate during sequential stimuli. A model of synaptotagmin1-Ca 2+ binding indicates that even with 10 µM free varicosity Ca 2+ , synaptogmin1 must be within tens of nanometers of channels to ensure occupation of all its Ca 2+ binding sites. Repetitive stimulation, which evokes short-term synaptic enhancement, does not modify probabilities of Ca 2+ fully occupying synaptotagmin1's C2 domains, suggesting that enhancement is not mediated by Ca 2+ -synaptotagmin1. We conclude that at spatio-temporal scale of fusion machines, Ca 2+ necessary for their activation is diffusion dominated.

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Ca ²⁺ stores and use-dependent facilitation of presynaptic Ca ²⁺ signaling

Cited by 6 publications

References 4 publications

Quantitation and Simulation of Single Action Potential-Evoked Ca²⁺Signals in CA1 Pyramidal Neuron Presynaptic Terminals

Quantitation and Simulation of Single Action Potential-Evoked Ca²⁺Signals in CA1 Pyramidal Neuron Presynaptic Terminals

Ionotropic receptors at hippocampal mossy fibers: roles in axonal excitability, synaptic transmission, and plasticity

Quantitation of single action potential-evoked Ca²⁺signals in CA1 pyramidal neuron presynaptic terminals

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Ca 2+ stores and use-dependent facilitation of presynaptic Ca 2+ signaling

Cited by 6 publications

References 4 publications

Quantitation and Simulation of Single Action Potential-Evoked Ca2+Signals in CA1 Pyramidal Neuron Presynaptic Terminals

Quantitation and Simulation of Single Action Potential-Evoked Ca2+Signals in CA1 Pyramidal Neuron Presynaptic Terminals

Ionotropic receptors at hippocampal mossy fibers: roles in axonal excitability, synaptic transmission, and plasticity

Quantitation of single action potential-evoked Ca2+signals in CA1 pyramidal neuron presynaptic terminals

Contact Info

Product

Resources

About

Ca ²⁺ stores and use-dependent facilitation of presynaptic Ca ²⁺ signaling

Quantitation and Simulation of Single Action Potential-Evoked Ca²⁺Signals in CA1 Pyramidal Neuron Presynaptic Terminals

Quantitation and Simulation of Single Action Potential-Evoked Ca²⁺Signals in CA1 Pyramidal Neuron Presynaptic Terminals

Quantitation of single action potential-evoked Ca²⁺signals in CA1 pyramidal neuron presynaptic terminals