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Publication : Characterization of the Astrocyte Calcium Response to Norepinephrine in the Ventral Tegmental Area.

First Author  Speggiorin M Year  2024
Journal  Cells Volume  14
Issue  1 PubMed ID  39791726
Mgi Jnum  J:383153 Mgi Id  MGI:7854157
Doi  10.3390/cells14010024 Citation  Speggiorin M, et al. (2024) Characterization of the Astrocyte Calcium Response to Norepinephrine in the Ventral Tegmental Area. Cells 14(1)
abstractText  Astrocytes from different brain regions respond with Ca(2+) 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(2+) response to NE at both soma and processes. Our results revealed that Gq-coupled alpha1 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(-/-) mice), we found that the astrocyte response to NE, even if reduced, is still present. We also found that in IP3R2(-/-) astrocytes, the residual Ca(2+) elevations elicited by NE depend on the release of Ca(2+) 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.
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