Calbindin-D28K limits dopamine release in ventral but not dorsal striatum by regulating Ca2+ availability and dopamine transporter function
The calcium-binding protein calbindin-D28K, or calb1, is expressed at higher levels by dopamine (DA) neurons originating in ventral tegmental area (VTA) than in adjacent substantia nigra pars compacta (SNc). Calb1 has received attention for a potential role in neuroprotection in Parkinson’s disease....
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
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American Chemical Society
2019
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| _version_ | 1826266126973140992 |
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| author | Brimblecombe, K Vietti-Michelina, S Platt, N Kastli, R Hnieno, A Gracie, C Cragg, S |
| author_facet | Brimblecombe, K Vietti-Michelina, S Platt, N Kastli, R Hnieno, A Gracie, C Cragg, S |
| author_sort | Brimblecombe, K |
| collection | OXFORD |
| description | The calcium-binding protein calbindin-D28K, or calb1, is expressed at higher levels by dopamine (DA) neurons originating in ventral tegmental area (VTA) than in adjacent substantia nigra pars compacta (SNc). Calb1 has received attention for a potential role in neuroprotection in Parkinson’s disease. The underlying physiological roles for calb1 are incompletely understood. We used cre-loxP technology to knockdown calb1 in mouse DA neurons to test whether calb1 governs axonal release of DA in striatum, detected using fast-scan cyclic voltammetry ex vivo. In ventral but not dorsal striatum, calb1 knockdown elevated DA release and modified the spatiotemporal coupling of Ca2+ entry to DA release. Furthermore, calb1 knockdown enhanced DA uptake but attenuated the impact of DA transporter (DAT) inhibition by cocaine on underlying DA release. These data reveal that calb1 acts through a range of mechanisms underpinning both DA release and uptake to limit DA transmission in ventral but not dorsal striatum. |
| first_indexed | 2024-03-06T20:34:13Z |
| format | Journal article |
| id | oxford-uuid:3213af3e-936d-4ced-86ee-354f0ec56877 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:34:13Z |
| publishDate | 2019 |
| publisher | American Chemical Society |
| record_format | dspace |
| spelling | oxford-uuid:3213af3e-936d-4ced-86ee-354f0ec568772022-03-26T13:11:50ZCalbindin-D28K limits dopamine release in ventral but not dorsal striatum by regulating Ca2+ availability and dopamine transporter functionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3213af3e-936d-4ced-86ee-354f0ec56877EnglishSymplectic Elements at OxfordAmerican Chemical Society2019Brimblecombe, KVietti-Michelina, SPlatt, NKastli, RHnieno, AGracie, CCragg, SThe calcium-binding protein calbindin-D28K, or calb1, is expressed at higher levels by dopamine (DA) neurons originating in ventral tegmental area (VTA) than in adjacent substantia nigra pars compacta (SNc). Calb1 has received attention for a potential role in neuroprotection in Parkinson’s disease. The underlying physiological roles for calb1 are incompletely understood. We used cre-loxP technology to knockdown calb1 in mouse DA neurons to test whether calb1 governs axonal release of DA in striatum, detected using fast-scan cyclic voltammetry ex vivo. In ventral but not dorsal striatum, calb1 knockdown elevated DA release and modified the spatiotemporal coupling of Ca2+ entry to DA release. Furthermore, calb1 knockdown enhanced DA uptake but attenuated the impact of DA transporter (DAT) inhibition by cocaine on underlying DA release. These data reveal that calb1 acts through a range of mechanisms underpinning both DA release and uptake to limit DA transmission in ventral but not dorsal striatum. |
| spellingShingle | Brimblecombe, K Vietti-Michelina, S Platt, N Kastli, R Hnieno, A Gracie, C Cragg, S Calbindin-D28K limits dopamine release in ventral but not dorsal striatum by regulating Ca2+ availability and dopamine transporter function |
| title | Calbindin-D28K limits dopamine release in ventral but not dorsal striatum by regulating Ca2+ availability and dopamine transporter function |
| title_full | Calbindin-D28K limits dopamine release in ventral but not dorsal striatum by regulating Ca2+ availability and dopamine transporter function |
| title_fullStr | Calbindin-D28K limits dopamine release in ventral but not dorsal striatum by regulating Ca2+ availability and dopamine transporter function |
| title_full_unstemmed | Calbindin-D28K limits dopamine release in ventral but not dorsal striatum by regulating Ca2+ availability and dopamine transporter function |
| title_short | Calbindin-D28K limits dopamine release in ventral but not dorsal striatum by regulating Ca2+ availability and dopamine transporter function |
| title_sort | calbindin d28k limits dopamine release in ventral but not dorsal striatum by regulating ca2 availability and dopamine transporter function |
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