Characterization of the Astrocyte Calcium Response to Norepinephrine in the Ventral Tegmental Area
Astrocytes from different brain regions respond with Ca<sup>2+</sup> elevations to the catecholamine norepinephrine (NE). However, whether this noradrenergic-mediated signaling is present in astrocytes from the ventral tegmental area (VTA), a dopaminergic circuit receiving noradrenergic...
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2024-12-01
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| author | Michele Speggiorin Angela Chiavegato Micaela Zonta Marta Gómez-Gonzalo |
| author_facet | Michele Speggiorin Angela Chiavegato Micaela Zonta Marta Gómez-Gonzalo |
| author_sort | Michele Speggiorin |
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| description | Astrocytes from different brain regions respond with Ca<sup>2+</sup> elevations to the catecholamine norepinephrine (NE). However, whether this noradrenergic-mediated signaling is present in astrocytes from the ventral tegmental area (VTA), a dopaminergic circuit receiving noradrenergic inputs, has not yet been investigated. To fill in this gap, we applied a pharmacological approach along with two-photon microscopy and an AAV strategy to express a genetically encoded calcium indicator in VTA astrocytes. We found that VTA astrocytes from both female and male young adult mice showed a strong Ca<sup>2+</sup> response to NE at both soma and processes. Our results revealed that Gq-coupled α1 adrenergic receptors, which elicit the production of IP3, are the main mediators of the astrocyte response. In mice lacking the IP3 receptor type-2 (IP3R2<sup>−/−</sup> mice), we found that the astrocyte response to NE, even if reduced, is still present. We also found that in IP3R2<sup>−/−</sup> astrocytes, the residual Ca<sup>2+</sup> elevations elicited by NE depend on the release of Ca<sup>2+</sup> from the endoplasmic reticulum, through IP3Rs different from IP3R2. In conclusion, our results reveal VTA astrocytes as novel targets of the noradrenergic signaling, opening to new interpretations of the cellular and molecular mechanisms that mediate the NE effects in the VTA. |
| format | Article |
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| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2024-12-01 |
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| spelling | doaj-art-2c2eedd9898f411d8193760f3c3872152025-01-10T13:16:17ZengMDPI AGCells2073-44092024-12-011412410.3390/cells14010024Characterization of the Astrocyte Calcium Response to Norepinephrine in the Ventral Tegmental AreaMichele Speggiorin0Angela Chiavegato1Micaela Zonta2Marta Gómez-Gonzalo3Department of Biomedical Sciences, Università degli Studi di Padova, 35131 Padova, ItalyDepartment of Biomedical Sciences, Università degli Studi di Padova, 35131 Padova, ItalyNeuroscience Institute, Section of Padova, National Research Council (CNR), 35131 Padova, ItalyNeuroscience Institute, Section of Padova, National Research Council (CNR), 35131 Padova, ItalyAstrocytes from different brain regions respond with Ca<sup>2+</sup> elevations to the catecholamine norepinephrine (NE). However, whether this noradrenergic-mediated signaling is present in astrocytes from the ventral tegmental area (VTA), a dopaminergic circuit receiving noradrenergic inputs, has not yet been investigated. To fill in this gap, we applied a pharmacological approach along with two-photon microscopy and an AAV strategy to express a genetically encoded calcium indicator in VTA astrocytes. We found that VTA astrocytes from both female and male young adult mice showed a strong Ca<sup>2+</sup> response to NE at both soma and processes. Our results revealed that Gq-coupled α1 adrenergic receptors, which elicit the production of IP3, are the main mediators of the astrocyte response. In mice lacking the IP3 receptor type-2 (IP3R2<sup>−/−</sup> mice), we found that the astrocyte response to NE, even if reduced, is still present. We also found that in IP3R2<sup>−/−</sup> astrocytes, the residual Ca<sup>2+</sup> elevations elicited by NE depend on the release of Ca<sup>2+</sup> from the endoplasmic reticulum, through IP3Rs different from IP3R2. In conclusion, our results reveal VTA astrocytes as novel targets of the noradrenergic signaling, opening to new interpretations of the cellular and molecular mechanisms that mediate the NE effects in the VTA.https://www.mdpi.com/2073-4409/14/1/24ventral tegmental areaastrocytecalciumnorepinephrineIP3 receptor |
| spellingShingle | Michele Speggiorin Angela Chiavegato Micaela Zonta Marta Gómez-Gonzalo Characterization of the Astrocyte Calcium Response to Norepinephrine in the Ventral Tegmental Area Cells ventral tegmental area astrocyte calcium norepinephrine IP3 receptor |
| title | Characterization of the Astrocyte Calcium Response to Norepinephrine in the Ventral Tegmental Area |
| title_full | Characterization of the Astrocyte Calcium Response to Norepinephrine in the Ventral Tegmental Area |
| title_fullStr | Characterization of the Astrocyte Calcium Response to Norepinephrine in the Ventral Tegmental Area |
| title_full_unstemmed | Characterization of the Astrocyte Calcium Response to Norepinephrine in the Ventral Tegmental Area |
| title_short | Characterization of the Astrocyte Calcium Response to Norepinephrine in the Ventral Tegmental Area |
| title_sort | characterization of the astrocyte calcium response to norepinephrine in the ventral tegmental area |
| topic | ventral tegmental area astrocyte calcium norepinephrine IP3 receptor |
| url | https://www.mdpi.com/2073-4409/14/1/24 |
| work_keys_str_mv | AT michelespeggiorin characterizationoftheastrocytecalciumresponsetonorepinephrineintheventraltegmentalarea AT angelachiavegato characterizationoftheastrocytecalciumresponsetonorepinephrineintheventraltegmentalarea AT micaelazonta characterizationoftheastrocytecalciumresponsetonorepinephrineintheventraltegmentalarea AT martagomezgonzalo characterizationoftheastrocytecalciumresponsetonorepinephrineintheventraltegmentalarea |