Photoactivatable AMPA for the study of glutamatergic neuronal transmission using two-photon excitation

Davide Deodato; Naeem Asad; Timothy M. Dore

doi:10.1039/d1ob01006a

Photoactivatable AMPA for the study of glutamatergic neuronal transmission using two-photon excitation

Davide Deodato, Naeem Asad, Timothy M. Dore

Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

We report a photoactivatable agonist of the AMPA subtype of ionotropic glutamate receptors, TMP-CyHQ-AMPA, which was designed to study the fast excitatory transmission between neurons. Upon visible light excitation, TMP-CyHQ-AMPA quantitatively released AMPA in high quantum yield on an ultra-short timescale. Intriguingly, the photolyisis can be carried out using 2-photon excitation (2PE) with remarkable efficiency, giving a two-photon uncaging action cross section (δ_u) value of 1.71 GM. TMP-CyHQ-AMPA is soluble in pysiological buffer and no hydrolysis was detected in the absence of light. Molecular docking experiments indicated that the photocaging strategy abolishes the affinity of AMPA for the GluR2 receptor and no GABAergic effects (as commonly observed in caged glutamates) are expected. TMP-CyHQ-AMPA can be used to study glutamatergic neuronal transmission with exceptional spatial-temporal resolution in complex tissue preparations.

Original language	English (US)
Pages (from-to)	5589-5594
Number of pages	6
Journal	Organic and Biomolecular Chemistry
Volume	19
Issue number	25
DOIs	https://doi.org/10.1039/d1ob01006a
State	Published - Jul 7 2021

ASJC Scopus subject areas

Biochemistry
Physical and Theoretical Chemistry
Organic Chemistry

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title = "Photoactivatable AMPA for the study of glutamatergic neuronal transmission using two-photon excitation",

abstract = "We report a photoactivatable agonist of the AMPA subtype of ionotropic glutamate receptors, TMP-CyHQ-AMPA, which was designed to study the fast excitatory transmission between neurons. Upon visible light excitation, TMP-CyHQ-AMPA quantitatively released AMPA in high quantum yield on an ultra-short timescale. Intriguingly, the photolyisis can be carried out using 2-photon excitation (2PE) with remarkable efficiency, giving a two-photon uncaging action cross section (δu) value of 1.71 GM. TMP-CyHQ-AMPA is soluble in pysiological buffer and no hydrolysis was detected in the absence of light. Molecular docking experiments indicated that the photocaging strategy abolishes the affinity of AMPA for the GluR2 receptor and no GABAergic effects (as commonly observed in caged glutamates) are expected. TMP-CyHQ-AMPA can be used to study glutamatergic neuronal transmission with exceptional spatial-temporal resolution in complex tissue preparations.",

author = "Davide Deodato and Naeem Asad and Dore, {Timothy M.}",

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T1 - Photoactivatable AMPA for the study of glutamatergic neuronal transmission using two-photon excitation

AU - Deodato, Davide

AU - Asad, Naeem

AU - Dore, Timothy M.

N1 - Publisher Copyright: © The Royal Society of Chemistry 2021.

PY - 2021/7/7

Y1 - 2021/7/7

N2 - We report a photoactivatable agonist of the AMPA subtype of ionotropic glutamate receptors, TMP-CyHQ-AMPA, which was designed to study the fast excitatory transmission between neurons. Upon visible light excitation, TMP-CyHQ-AMPA quantitatively released AMPA in high quantum yield on an ultra-short timescale. Intriguingly, the photolyisis can be carried out using 2-photon excitation (2PE) with remarkable efficiency, giving a two-photon uncaging action cross section (δu) value of 1.71 GM. TMP-CyHQ-AMPA is soluble in pysiological buffer and no hydrolysis was detected in the absence of light. Molecular docking experiments indicated that the photocaging strategy abolishes the affinity of AMPA for the GluR2 receptor and no GABAergic effects (as commonly observed in caged glutamates) are expected. TMP-CyHQ-AMPA can be used to study glutamatergic neuronal transmission with exceptional spatial-temporal resolution in complex tissue preparations.

AB - We report a photoactivatable agonist of the AMPA subtype of ionotropic glutamate receptors, TMP-CyHQ-AMPA, which was designed to study the fast excitatory transmission between neurons. Upon visible light excitation, TMP-CyHQ-AMPA quantitatively released AMPA in high quantum yield on an ultra-short timescale. Intriguingly, the photolyisis can be carried out using 2-photon excitation (2PE) with remarkable efficiency, giving a two-photon uncaging action cross section (δu) value of 1.71 GM. TMP-CyHQ-AMPA is soluble in pysiological buffer and no hydrolysis was detected in the absence of light. Molecular docking experiments indicated that the photocaging strategy abolishes the affinity of AMPA for the GluR2 receptor and no GABAergic effects (as commonly observed in caged glutamates) are expected. TMP-CyHQ-AMPA can be used to study glutamatergic neuronal transmission with exceptional spatial-temporal resolution in complex tissue preparations.

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Photoactivatable AMPA for the study of glutamatergic neuronal transmission using two-photon excitation

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