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The Residence of Synaptically Released Dopamine on D2-Autoreceptors

18 Pages Posted: 10 Feb 2021 Publication Status: Published

See all articles by Alec F. Condon

Alec F. Condon

Oregon Health and Science University - Vollum Institute

Brooks G. Robinson

Oregon Health and Science University - Vollum Institute

Naeem Asad

Oregon Health and Science University - Vollum Institute

Timothy M. Dore

New York University Abu Dhabi; University of Georgia

Lin Tian

Oregon Health and Science University - Vollum Institute

John T. Williams

Oregon Health and Science University - Vollum Institute

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Abstract

Neuromodulation mediated by synaptically released endogenous transmitters acting in G protein coupled receptors (GPCRs) is slow primarily because of multistep downstream signaling. What is not known is the spatial and temporal kinetics of transmitter and receptor interaction. The present work used the combination of the dopamine sensor, dLight, to detect the spatial release and diffusion of dopamine and a caged form of a D2-dopamine receptor antagonist, CyHQ-sulpiride, to rapidly block the D2-autoreceptors. Photoactivation of the CyHQ-sulpiride blocked receptors in milliseconds such that the time course of dopamine/receptor interaction was mapped onto the downstream signaling. The results show that highly localized release, but not dopamine diffusion, defines the time course of the functional interaction between dopamine and D2-autoreceptors, which determines downstream inhibition.

Suggested Citation

Condon, Alec F. and Robinson, Brooks G. and Asad, Naeem and Dore, Timothy M. and Tian, Lin and Williams, John T., The Residence of Synaptically Released Dopamine on D2-Autoreceptors. Available at SSRN: https://ssrn.com/abstract=3783407 or http://dx.doi.org/10.2139/ssrn.3783407
This version of the paper has not been formally peer reviewed.

Alec F. Condon

Oregon Health and Science University - Vollum Institute ( email )

Marquam Hill Campus
Portland, OR 97239
United States

Brooks G. Robinson

Oregon Health and Science University - Vollum Institute ( email )

Marquam Hill Campus
Portland, OR 97239
United States

Naeem Asad

Oregon Health and Science University - Vollum Institute ( email )

Marquam Hill Campus
Portland, OR 97239
United States

Timothy M. Dore

New York University Abu Dhabi ( email )

Saadiyat Island
PO Box 129188
Abu Dhabi
United Arab Emirates

University of Georgia ( email )

Athens, GA 30602
United States

Lin Tian

Oregon Health and Science University - Vollum Institute

Marquam Hill Campus
Portland, OR 97239
United States

John T. Williams (Contact Author)

Oregon Health and Science University - Vollum Institute ( email )

Marquam Hill Campus
Portland, OR 97239
United States

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