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Ultrafast glutamate sensors resolve high-frequency release at Schaffer collateral synapses

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Ultrafast glutamate sensors resolve high-frequency release at Schaffer collateral synapses. / Helassa, Nordine; Dürst, Céline D; Coates, Catherine; Kerruth, Silke; Arif, Urwa; Schulze, Christian; Wiegert, J Simon; Geeves, Michael; Oertner, Thomas G; Török, Katalin.

In: P NATL ACAD SCI USA, Vol. 115, No. 21, 22.05.2018, p. 5594-5599.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Helassa, N, Dürst, CD, Coates, C, Kerruth, S, Arif, U, Schulze, C, Wiegert, JS, Geeves, M, Oertner, TG & Török, K 2018, 'Ultrafast glutamate sensors resolve high-frequency release at Schaffer collateral synapses', P NATL ACAD SCI USA, vol. 115, no. 21, pp. 5594-5599. https://doi.org/10.1073/pnas.1720648115

APA

Helassa, N., Dürst, C. D., Coates, C., Kerruth, S., Arif, U., Schulze, C., Wiegert, J. S., Geeves, M., Oertner, T. G., & Török, K. (2018). Ultrafast glutamate sensors resolve high-frequency release at Schaffer collateral synapses. P NATL ACAD SCI USA, 115(21), 5594-5599. https://doi.org/10.1073/pnas.1720648115

Vancouver

Helassa N, Dürst CD, Coates C, Kerruth S, Arif U, Schulze C et al. Ultrafast glutamate sensors resolve high-frequency release at Schaffer collateral synapses. P NATL ACAD SCI USA. 2018 May 22;115(21):5594-5599. https://doi.org/10.1073/pnas.1720648115

Bibtex

@article{3fc47cc32d2048818646f3dd2142aef1,
title = "Ultrafast glutamate sensors resolve high-frequency release at Schaffer collateral synapses",
abstract = "Glutamatergic synapses display a rich repertoire of plasticity mechanisms on many different time scales, involving dynamic changes in the efficacy of transmitter release as well as changes in the number and function of postsynaptic glutamate receptors. The genetically encoded glutamate sensor iGluSnFR enables visualization of glutamate release from presynaptic terminals at frequencies up to ∼10 Hz. However, to resolve glutamate dynamics during high-frequency bursts, faster indicators are required. Here, we report the development of fast (iGlu f ) and ultrafast (iGlu u ) variants with comparable brightness but increased Kd for glutamate (137 μM and 600 μM, respectively). Compared with iGluSnFR, iGlu u has a sixfold faster dissociation rate in vitro and fivefold faster kinetics in synapses. Fitting a three-state model to kinetic data, we identify the large conformational change after glutamate binding as the rate-limiting step. In rat hippocampal slice culture stimulated at 100 Hz, we find that iGlu u is sufficiently fast to resolve individual glutamate release events, revealing that glutamate is rapidly cleared from the synaptic cleft. Depression of iGlu u responses during 100-Hz trains correlates with depression of postsynaptic EPSPs, indicating that depression during high-frequency stimulation is purely presynaptic in origin. At individual boutons, the recovery from depression could be predicted from the amount of glutamate released on the second pulse (paired pulse facilitation/depression), demonstrating differential frequency-dependent filtering of spike trains at Schaffer collateral boutons.",
keywords = "Animals, Glutamic Acid, Hippocampus, Male, Neuronal Plasticity, Patch-Clamp Techniques, Presynaptic Terminals, Pyramidal Cells, Rats, Rats, Wistar, Synapses, Synaptic Transmission, Journal Article, Research Support, Non-U.S. Gov't",
author = "Nordine Helassa and D{\"u}rst, {C{\'e}line D} and Catherine Coates and Silke Kerruth and Urwa Arif and Christian Schulze and Wiegert, {J Simon} and Michael Geeves and Oertner, {Thomas G} and Katalin T{\"o}r{\"o}k",
note = "Copyright {\textcopyright} 2018 the Author(s). Published by PNAS.",
year = "2018",
month = may,
day = "22",
doi = "10.1073/pnas.1720648115",
language = "English",
volume = "115",
pages = "5594--5599",
journal = "P NATL ACAD SCI USA",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "21",

}

RIS

TY - JOUR

T1 - Ultrafast glutamate sensors resolve high-frequency release at Schaffer collateral synapses

AU - Helassa, Nordine

AU - Dürst, Céline D

AU - Coates, Catherine

AU - Kerruth, Silke

AU - Arif, Urwa

AU - Schulze, Christian

AU - Wiegert, J Simon

AU - Geeves, Michael

AU - Oertner, Thomas G

AU - Török, Katalin

N1 - Copyright © 2018 the Author(s). Published by PNAS.

PY - 2018/5/22

Y1 - 2018/5/22

N2 - Glutamatergic synapses display a rich repertoire of plasticity mechanisms on many different time scales, involving dynamic changes in the efficacy of transmitter release as well as changes in the number and function of postsynaptic glutamate receptors. The genetically encoded glutamate sensor iGluSnFR enables visualization of glutamate release from presynaptic terminals at frequencies up to ∼10 Hz. However, to resolve glutamate dynamics during high-frequency bursts, faster indicators are required. Here, we report the development of fast (iGlu f ) and ultrafast (iGlu u ) variants with comparable brightness but increased Kd for glutamate (137 μM and 600 μM, respectively). Compared with iGluSnFR, iGlu u has a sixfold faster dissociation rate in vitro and fivefold faster kinetics in synapses. Fitting a three-state model to kinetic data, we identify the large conformational change after glutamate binding as the rate-limiting step. In rat hippocampal slice culture stimulated at 100 Hz, we find that iGlu u is sufficiently fast to resolve individual glutamate release events, revealing that glutamate is rapidly cleared from the synaptic cleft. Depression of iGlu u responses during 100-Hz trains correlates with depression of postsynaptic EPSPs, indicating that depression during high-frequency stimulation is purely presynaptic in origin. At individual boutons, the recovery from depression could be predicted from the amount of glutamate released on the second pulse (paired pulse facilitation/depression), demonstrating differential frequency-dependent filtering of spike trains at Schaffer collateral boutons.

AB - Glutamatergic synapses display a rich repertoire of plasticity mechanisms on many different time scales, involving dynamic changes in the efficacy of transmitter release as well as changes in the number and function of postsynaptic glutamate receptors. The genetically encoded glutamate sensor iGluSnFR enables visualization of glutamate release from presynaptic terminals at frequencies up to ∼10 Hz. However, to resolve glutamate dynamics during high-frequency bursts, faster indicators are required. Here, we report the development of fast (iGlu f ) and ultrafast (iGlu u ) variants with comparable brightness but increased Kd for glutamate (137 μM and 600 μM, respectively). Compared with iGluSnFR, iGlu u has a sixfold faster dissociation rate in vitro and fivefold faster kinetics in synapses. Fitting a three-state model to kinetic data, we identify the large conformational change after glutamate binding as the rate-limiting step. In rat hippocampal slice culture stimulated at 100 Hz, we find that iGlu u is sufficiently fast to resolve individual glutamate release events, revealing that glutamate is rapidly cleared from the synaptic cleft. Depression of iGlu u responses during 100-Hz trains correlates with depression of postsynaptic EPSPs, indicating that depression during high-frequency stimulation is purely presynaptic in origin. At individual boutons, the recovery from depression could be predicted from the amount of glutamate released on the second pulse (paired pulse facilitation/depression), demonstrating differential frequency-dependent filtering of spike trains at Schaffer collateral boutons.

KW - Animals

KW - Glutamic Acid

KW - Hippocampus

KW - Male

KW - Neuronal Plasticity

KW - Patch-Clamp Techniques

KW - Presynaptic Terminals

KW - Pyramidal Cells

KW - Rats

KW - Rats, Wistar

KW - Synapses

KW - Synaptic Transmission

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1073/pnas.1720648115

DO - 10.1073/pnas.1720648115

M3 - SCORING: Journal article

C2 - 29735711

VL - 115

SP - 5594

EP - 5599

JO - P NATL ACAD SCI USA

JF - P NATL ACAD SCI USA

SN - 0027-8424

IS - 21

ER -