Fernández de la Puebla Mario, Zhang Xiaoyi, Nagelhus Erlend A, Bjørås Magnar, Tang Wannan
Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway.
Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, 0372 Oslo, Norway.
Cells. 2025 Jul 18;14(14):1103. doi: 10.3390/cells14141103.
Accumulating studies have shown that astrocytes are essential for regulating neurons at both synaptic and circuit levels. The main mechanism of brain astrocytic intracellular Ca activity is through the release of Ca via the inositol 1,4,5-trisphosphate receptor type 2 (IP3R2) from the endoplasmic reticulum (ER). Studies using IP3R2 knockout mouse models () have shown that eliminating IP3R2 leads to a significant reduction in astrocytic Ca activity However, there is ongoing controversy regarding the effect of this IP3R2-dependent reduction in astrocytic Ca transients on neuronal activity. In our study, we employed dual-color two-photon Ca imaging to study astrocytes and neurons simultaneously in vibrissa somatosensory cortex (vS1) in awake-behaving wild-type and mice. We systematically characterized and compared both recorded astrocytic and neuronal Ca activities in wild-type and mice during various animal behaviors, particularly during the transition period from stillness to locomotion. We report that vS1 astrocytic Ca elevation in both wild-type and mice was significantly modulated by free whisking and locomotion. However, vS1 neurons were only significantly modulated by locomotion in wild-type mice, but not in mice. Our study suggests a non-synaptic modulatory mechanism on functions of astrocytic IP3R2-dependent Ca transients to local neurons.
越来越多的研究表明，星形胶质细胞在突触和回路水平上对调节神经元至关重要。脑星形胶质细胞内钙活动的主要机制是通过内质网（ER）中的2型肌醇1,4,5-三磷酸受体（IP3R2）释放钙。使用IP3R2基因敲除小鼠模型的研究表明，消除IP3R2会导致星形胶质细胞钙活动显著降低。然而，关于这种依赖IP3R2的星形胶质细胞钙瞬变减少对神经元活动的影响，目前仍存在争议。在我们的研究中，我们采用双色双光子钙成像技术，在清醒行为的野生型和[此处缺失特定小鼠类型信息]小鼠的触须体感皮层（vS1）中同时研究星形胶质细胞和神经元。我们系统地表征和比较了野生型和[此处缺失特定小鼠类型信息]小鼠在各种动物行为期间，特别是从静止到运动的过渡期间记录的星形胶质细胞和神经元的钙活动。我们报告说，野生型和[此处缺失特定小鼠类型信息]小鼠的vS1星形胶质细胞钙升高都受到自由触须运动和运动的显著调节。然而，vS1神经元仅在野生型小鼠中受到运动的显著调节，而在[此处缺失特定小鼠类型信息]小鼠中则没有。我们的研究表明了一种对局部神经元的星形胶质细胞IP3R2依赖性钙瞬变功能的非突触调节机制。
