Laboratory for Neuron-Glia Circuitry, RIKEN Center for Brain Science, Wako, Japan.
Center for Translational Neuromedicine, Faculty of Medical and Health Sciences, University of Copenhagen, Copenhagen, Denmark.
Front Neural Circuits. 2021 Mar 22;15:658343. doi: 10.3389/fncir.2021.658343. eCollection 2021.
Astrocytes elicit transient Ca elevations induced by G protein-coupled receptors (GPCRs), yet their role remains unknown. To address this, transgenic mice with astrocytic expression of the optogenetic Gq-type GPCR, Optoα1AR, were established, in which transient Ca elevations similar to those in wild type mice were induced by brief blue light illumination. Activation of cortical astrocytes resulted in an adenosine A1 receptor-dependent inhibition of neuronal activity. Moreover, sensory stimulation with astrocytic activation induced long-term depression of sensory evoked response. At the behavioral level, repeated astrocytic activation in the anterior cortex gradually affected novel open field exploratory behavior, and remote memory was enhanced in a novel object recognition task. These effects were blocked by A1 receptor antagonism. Together, we demonstrate that GPCR-triggered Ca elevation in cortical astrocytes has causal impacts on neuronal activity and behavior.
星形胶质细胞可引发 G 蛋白偶联受体 (GPCR) 诱导的短暂钙升高，但它们的作用仍不清楚。为了解决这个问题，我们建立了星形胶质细胞表达光遗传学 Gq 型 GPCR（Optoα1AR）的转基因小鼠，在这些小鼠中，短暂的钙升高可通过短暂的蓝光照射诱导，类似于野生型小鼠。皮质星形胶质细胞的激活导致腺苷 A1 受体依赖性神经元活动抑制。此外，用星形胶质细胞激活进行感觉刺激会诱导感觉诱发反应的长期抑制。在行为水平上，在前皮质中重复的星形胶质细胞激活逐渐影响新的开阔场探索行为，并且在新物体识别任务中增强了远程记忆。这些作用被 A1 受体拮抗剂阻断。总之，我们证明了皮质星形胶质细胞中 GPCR 触发的钙升高对神经元活动和行为有因果影响。
