Interrogating the Spatiotemporal Landscape of Neuromodulatory GPCR Signaling by Real-Time Imaging of cAMP in Intact Neurons and Circuits
Summary: Modulation of neuronal circuits is key to information processing in the brain. The majority of neuromodulators exert their effects by activating G-protein-coupled receptors (GPCRs) that control the production of second messengers directly impacting cellular physiology. How numerous GPCRs in...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-01-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717318314 |
| _version_ | 1818200126321065984 |
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| author | Brian S. Muntean Stefano Zucca Courtney M. MacMullen Maria T. Dao Caitlin Johnston Hideki Iwamoto Randy D. Blakely Ronald L. Davis Kirill A. Martemyanov |
| author_facet | Brian S. Muntean Stefano Zucca Courtney M. MacMullen Maria T. Dao Caitlin Johnston Hideki Iwamoto Randy D. Blakely Ronald L. Davis Kirill A. Martemyanov |
| author_sort | Brian S. Muntean |
| collection | DOAJ |
| description | Summary: Modulation of neuronal circuits is key to information processing in the brain. The majority of neuromodulators exert their effects by activating G-protein-coupled 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. : Muntean et al. develop an in vivo reagent to study processing of neurotransmitter GPCR signals by monitoring real-time dynamics of cAMP responses. They demonstrate application of this approach, in combination with CRISPR/Cas9 gene editing and optogenetics, to interrogate the functional organization of a striatal circuit. Keywords: cAMP, GPCR, neuromodulation, dopamine, striatum, imaging, optogenetics |
| first_indexed | 2024-12-12T02:32:42Z |
| format | Article |
| id | doaj.art-207ebaaf212843c9b8f60c16dd36bffd |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-12T02:32:42Z |
| publishDate | 2018-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-207ebaaf212843c9b8f60c16dd36bffd2022-12-22T00:41:21ZengElsevierCell Reports2211-12472018-01-01221255268Interrogating the Spatiotemporal Landscape of Neuromodulatory GPCR Signaling by Real-Time Imaging of cAMP in Intact Neurons and CircuitsBrian S. Muntean0Stefano Zucca1Courtney M. MacMullen2Maria T. Dao3Caitlin Johnston4Hideki Iwamoto5Randy D. Blakely6Ronald L. Davis7Kirill A. Martemyanov8Department of Neuroscience, The Scripps Research Institute, Jupiter, FL 33458 USADepartment of Neuroscience, The Scripps Research Institute, Jupiter, FL 33458 USADepartment of Neuroscience, The Scripps Research Institute, Jupiter, FL 33458 USADepartment of Neuroscience, The Scripps Research Institute, Jupiter, FL 33458 USADepartment of Neuroscience, The Scripps Research Institute, Jupiter, FL 33458 USADepartment of Biomedical Science and Brain Institute, Charles E. Schmidt College of Medicine, Florida Atlantic University, Jupiter, FL 33458, USADepartment of Biomedical Science and Brain Institute, Charles E. Schmidt College of Medicine, Florida Atlantic University, Jupiter, FL 33458, USADepartment of Neuroscience, The Scripps Research Institute, Jupiter, FL 33458 USADepartment of Neuroscience, The Scripps Research Institute, Jupiter, FL 33458 USA; Corresponding authorSummary: Modulation of neuronal circuits is key to information processing in the brain. The majority of neuromodulators exert their effects by activating G-protein-coupled 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. : Muntean et al. develop an in vivo reagent to study processing of neurotransmitter GPCR signals by monitoring real-time dynamics of cAMP responses. They demonstrate application of this approach, in combination with CRISPR/Cas9 gene editing and optogenetics, to interrogate the functional organization of a striatal circuit. Keywords: cAMP, GPCR, neuromodulation, dopamine, striatum, imaging, optogeneticshttp://www.sciencedirect.com/science/article/pii/S2211124717318314 |
| spellingShingle | Brian S. Muntean Stefano Zucca Courtney M. MacMullen Maria T. Dao Caitlin Johnston Hideki Iwamoto Randy D. Blakely Ronald L. Davis Kirill A. Martemyanov Interrogating the Spatiotemporal Landscape of Neuromodulatory GPCR Signaling by Real-Time Imaging of cAMP in Intact Neurons and Circuits Cell Reports |
| title | Interrogating the Spatiotemporal Landscape of Neuromodulatory GPCR Signaling by Real-Time Imaging of cAMP in Intact Neurons and Circuits |
| title_full | Interrogating the Spatiotemporal Landscape of Neuromodulatory GPCR Signaling by Real-Time Imaging of cAMP in Intact Neurons and Circuits |
| title_fullStr | Interrogating the Spatiotemporal Landscape of Neuromodulatory GPCR Signaling by Real-Time Imaging of cAMP in Intact Neurons and Circuits |
| title_full_unstemmed | Interrogating the Spatiotemporal Landscape of Neuromodulatory GPCR Signaling by Real-Time Imaging of cAMP in Intact Neurons and Circuits |
| title_short | Interrogating the Spatiotemporal Landscape of Neuromodulatory GPCR Signaling by Real-Time Imaging of cAMP in Intact Neurons and Circuits |
| title_sort | interrogating the spatiotemporal landscape of neuromodulatory gpcr signaling by real time imaging of camp in intact neurons and circuits |
| url | http://www.sciencedirect.com/science/article/pii/S2211124717318314 |
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