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Proc Natl Acad Sci U S A ; 117(12): 6831-6835, 2020 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-32152102

RESUMO

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.


Assuntos
Glutamatos/farmacologia , Indóis/farmacologia , Aprendizagem/fisiologia , Microfluídica , Neurônios/fisiologia , Neurotransmissores/farmacologia , Animais , Aprendizagem/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Neuroquímica , Neurônios/efeitos dos fármacos , Fotoquímica , Fotólise , Receptores de GABA/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo
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