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Interrogating the Spatiotemporal Landscape of Neuromodulatory GPCR Signaling by Real-Time Imaging of cAMP in Intact Neurons and Circuits

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Date Issued:
2018
Summary:
Modulation of neuronal circuits is key to information processing in the brain. The majority of neuromodulators exert their effects by activating G-proteincoupled receptors (GPCRs) that control the production of second messengers directly impacting cellular physiology. How numerous GPCRs integrate neuromodulatory inputs while accommodating diversity of incoming signals is poorly understood. In this study, we develop an in vivo tool and analytical suite for analyzing GPCR responses by monitoring the dynamics of a key second messenger, cyclic AMP (cAMP), with excellent quantitative and spatiotemporal resolution in various neurons. Using this imaging approach in combination with CRISPR/Cas9 editing and optogenetics, we interrogate neuromodulatory mechanisms of defined populations of neurons in an intact mesolimbic reward circuit and describe how individual inputs generate discrete second-messenger signatures in a cell- and receptor- specific fashion. This offers a resource for studying native neuronal GPCR signaling in real time.
Title: Interrogating the Spatiotemporal Landscape of Neuromodulatory GPCR Signaling by Real-Time Imaging of cAMP in Intact Neurons and Circuits.
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Name(s): Brian S. Muntean
Stefano Zucca
Courtney M. MacMullen
Maria T. Dao
Caitlin Johnston
Hideki Iwamoto
Randy D. Blakely
Ronald L. Davis
Kirill A. Martemyanov
Type of Resource: text
Genre: Article
Date Issued: 2018
Publisher: Cell Press
Physical Form: pdf
Extent: 15 p.
Language(s): English
Summary: Modulation of neuronal circuits is key to information processing in the brain. The majority of neuromodulators exert their effects by activating G-proteincoupled receptors (GPCRs) that control the production of second messengers directly impacting cellular physiology. How numerous GPCRs integrate neuromodulatory inputs while accommodating diversity of incoming signals is poorly understood. In this study, we develop an in vivo tool and analytical suite for analyzing GPCR responses by monitoring the dynamics of a key second messenger, cyclic AMP (cAMP), with excellent quantitative and spatiotemporal resolution in various neurons. Using this imaging approach in combination with CRISPR/Cas9 editing and optogenetics, we interrogate neuromodulatory mechanisms of defined populations of neurons in an intact mesolimbic reward circuit and describe how individual inputs generate discrete second-messenger signatures in a cell- and receptor- specific fashion. This offers a resource for studying native neuronal GPCR signaling in real time.
Identifier: FAUIR000525 (IID)
Persistent Link to This Record: http://purl.flvc.org/fau/fd/FAUIR000525
Host Institution: FAU

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