AAV-compatible optogenetic tools for activating endogenous calcium channels in vivo
Abstract Calcium ions (Ca2+) play pivotal roles in regulating diverse brain functions, including cognition, emotion, locomotion, and learning and memory. These functions are intricately regulated by a variety of Ca2+-dependent cellular processes, encompassing synaptic plasticity, neuro/gliotransmitt...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-10-01
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| Series: | Molecular Brain |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13041-023-01061-7 |
| _version_ | 1797451076902846464 |
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| author | Yeon Hee Kook Hyoin Lee Jinsu Lee Yeonji Jeong Jaerang Rho Won Do Heo Sangkyu Lee |
| author_facet | Yeon Hee Kook Hyoin Lee Jinsu Lee Yeonji Jeong Jaerang Rho Won Do Heo Sangkyu Lee |
| author_sort | Yeon Hee Kook |
| collection | DOAJ |
| description | Abstract Calcium ions (Ca2+) play pivotal roles in regulating diverse brain functions, including cognition, emotion, locomotion, and learning and memory. These functions are intricately regulated by a variety of Ca2+-dependent cellular processes, encompassing synaptic plasticity, neuro/gliotransmitter release, and gene expression. In our previous work, we developed ‘monster OptoSTIM1’ (monSTIM1), an improved OptoSTIM1 that selectively activates Ca2+-release–activated Ca2+ (CRAC) channels in the plasma membrane through blue light, allowing precise control over intracellular Ca2+ signaling and specific brain functions. However, the large size of the coding sequence of monSTIM1 poses a limitation for its widespread use, as it exceeds the packaging capacity of adeno-associated virus (AAV). To address this constraint, we have introduced monSTIM1 variants with reduced coding sequence sizes and established AAV-based systems for expressing them in neurons and glial cells in the mouse brain. Upon expression by AAVs, these monSTIM1 variants significantly increased the expression levels of cFos in neurons and astrocytes in the hippocampal CA1 region following non-invasive light illumination. The use of monSTIM1 variants offers a promising avenue for investigating the spatiotemporal roles of Ca2+-mediated cellular activities in various brain functions. Furthermore, this toolkit holds potential as a therapeutic strategy for addressing brain disorders associated with aberrant Ca2+ signaling. |
| first_indexed | 2024-03-09T14:48:46Z |
| format | Article |
| id | doaj.art-d6a1b78b16564f3da613eeb823b102d2 |
| institution | Directory Open Access Journal |
| issn | 1756-6606 |
| language | English |
| last_indexed | 2024-03-09T14:48:46Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Brain |
| spelling | doaj.art-d6a1b78b16564f3da613eeb823b102d22023-11-26T14:35:55ZengBMCMolecular Brain1756-66062023-10-0116111610.1186/s13041-023-01061-7AAV-compatible optogenetic tools for activating endogenous calcium channels in vivoYeon Hee Kook0Hyoin Lee1Jinsu Lee2Yeonji Jeong3Jaerang Rho4Won Do Heo5Sangkyu Lee6Center for Cognition and Sociality, Institute for Basic Science (IBS)Center for Cognition and Sociality, Institute for Basic Science (IBS)Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST)Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST)Department of Bioscience and Biotechnology, Graduate School, Chungnam National UniversityDepartment of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST)Center for Cognition and Sociality, Institute for Basic Science (IBS)Abstract Calcium ions (Ca2+) play pivotal roles in regulating diverse brain functions, including cognition, emotion, locomotion, and learning and memory. These functions are intricately regulated by a variety of Ca2+-dependent cellular processes, encompassing synaptic plasticity, neuro/gliotransmitter release, and gene expression. In our previous work, we developed ‘monster OptoSTIM1’ (monSTIM1), an improved OptoSTIM1 that selectively activates Ca2+-release–activated Ca2+ (CRAC) channels in the plasma membrane through blue light, allowing precise control over intracellular Ca2+ signaling and specific brain functions. However, the large size of the coding sequence of monSTIM1 poses a limitation for its widespread use, as it exceeds the packaging capacity of adeno-associated virus (AAV). To address this constraint, we have introduced monSTIM1 variants with reduced coding sequence sizes and established AAV-based systems for expressing them in neurons and glial cells in the mouse brain. Upon expression by AAVs, these monSTIM1 variants significantly increased the expression levels of cFos in neurons and astrocytes in the hippocampal CA1 region following non-invasive light illumination. The use of monSTIM1 variants offers a promising avenue for investigating the spatiotemporal roles of Ca2+-mediated cellular activities in various brain functions. Furthermore, this toolkit holds potential as a therapeutic strategy for addressing brain disorders associated with aberrant Ca2+ signaling.https://doi.org/10.1186/s13041-023-01061-7Calcium ionOptogeneticsAdeno-associated virusNeuronsGlial cells |
| spellingShingle | Yeon Hee Kook Hyoin Lee Jinsu Lee Yeonji Jeong Jaerang Rho Won Do Heo Sangkyu Lee AAV-compatible optogenetic tools for activating endogenous calcium channels in vivo Molecular Brain Calcium ion Optogenetics Adeno-associated virus Neurons Glial cells |
| title | AAV-compatible optogenetic tools for activating endogenous calcium channels in vivo |
| title_full | AAV-compatible optogenetic tools for activating endogenous calcium channels in vivo |
| title_fullStr | AAV-compatible optogenetic tools for activating endogenous calcium channels in vivo |
| title_full_unstemmed | AAV-compatible optogenetic tools for activating endogenous calcium channels in vivo |
| title_short | AAV-compatible optogenetic tools for activating endogenous calcium channels in vivo |
| title_sort | aav compatible optogenetic tools for activating endogenous calcium channels in vivo |
| topic | Calcium ion Optogenetics Adeno-associated virus Neurons Glial cells |
| url | https://doi.org/10.1186/s13041-023-01061-7 |
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