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Proc Natl Acad Sci U S A. 2020 Mar 24;117(12):6831-6835. doi: 10.1073/pnas.1920869117. Epub 2020 Mar 9.

Optofluidic control of rodent learning using cloaked caged glutamate.

Author information

1
Neuroscience Paris Seine, Institut de Biologie Paris Seine, Sorbonne Université, 75005 Paris, France.
2
Department of Neuroscience, Mount Sinai School of Medicine, New York, NY 10029.
3
Neuroscience Paris Seine, Institut de Biologie Paris Seine, Sorbonne Université, 75005 Paris, France; almourot@gmail.com graham.davies@mssm.edu.
4
Department of Neuroscience, Mount Sinai School of Medicine, New York, NY 10029 almourot@gmail.com graham.davies@mssm.edu.

Abstract

Glutamate is the major excitatory neurotransmitter in the brain, and photochemical release of glutamate (or uncaging) is a chemical technique widely used by biologists to interrogate its physiology. A basic prerequisite of these optical probes is bio-inertness before photolysis. However, all caged glutamates are known to have strong antagonism toward receptors of γ-aminobutyric acid, the major inhibitory transmitter. We have developed a caged glutamate probe that is inert toward these receptors at concentrations that are effective for photolysis with violet light. Pharmacological tests in vitro revealed that attachment of a fifth-generation (G5) dendrimer (i.e., cloaking) to the widely used 4-methoxy-7-nitro-indolinyl(MNI)-Glu probe prevented such off-target effects while not changing the photochemical properties of MNI-Glu significantly. G5-MNI-Glu was used with optofluidic delivery to stimulate dopamine neurons of the ventral tegmental area of freely moving mice in a conditioned place-preference protocol so as to mediate Pavlovian conditioning.

KEYWORDS:

GABA-A antagonism; biologically inert; caged glutamate; conditioned place-preference; optofluidics

PMID:
32152102
DOI:
10.1073/pnas.1920869117

Conflict of interest statement

The authors declare no competing interest.

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