Wu Ai-Mei, Zhang Jing-Ya, Lun Wei-Zhong, Geng Zhi, Yang Ye, Wu Jun-Cang, Chen Gui-Hai
Department of Neurology (Sleep Disorders), The Affiliated Chaohu Hospital of Anhui Medical University, Hefei, Anhui, 230011, China.
Department of Neurology, The Second People's Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, Anhui, 230011, China.
Neurobiol Stress. 2024 Oct 4;33:100676. doi: 10.1016/j.ynstr.2024.100676. eCollection 2024 Nov.
Astrocytes play significant roles in regulating the central stress response. Chronic stress impairs the structure and function of astrocytes in many brain regions such as media prefrontal cortex (mPFC) in multiple neuropsychiatric conditions, but the astrocytic dynamics on the timescale of behavior remains unclear. Here, we recorded mPFC astrocytic activity in freely behaving mice and found that astrocytes are activated immediately by different aversive stimuli. Astrocyte specific GCaMP6s calcium indicator were virally expressed in mPFC astrocytes and fiber photometry experiments revealed that astrocytes are activated by tail-restraint (TRT), foot shock (FS), open arm exploration, stressor of height, predator odor and social defeat (SD) stress. ΔF/F analyses demonstrated that an unpredictable stimulus such as elevated platform stress (EPS) at the initial encounter induced the most intense and rapid changes in astrocytic calcium activity, while a predictable 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) stimulus resulted in the weakest response with a longer peak latency. In TRT, FS or SD test, a somatic stimulus led to higher average calcium activity level and faster average peak latency in repeated trails. Similar to TMT stimulus, astrocytic calcium activity in elevated plus maze (EPM) test exhibited a smaller average change in amplitude and the longest peak latency during open arm exploration. Moreover, astrocytic calcium activity exhibited different changes across behavioral states in SD tests. Our findings show that mPFC astrocytes exhibit distinct patterns of calcium activity in response to various negative stimuli, indicating that the dynamic activity of astrocytes may reflect the stress-related behavioral state under different stimulus conditions.
星形胶质细胞在调节中枢应激反应中发挥着重要作用。在多种神经精神疾病中，慢性应激会损害许多脑区（如内侧前额叶皮质（mPFC））中星形胶质细胞的结构和功能，但行为时间尺度上的星形胶质细胞动态变化仍不清楚。在这里，我们记录了自由活动小鼠的mPFC星形胶质细胞活动，发现星形胶质细胞会被不同的厌恶刺激立即激活。在mPFC星形胶质细胞中通过病毒表达星形胶质细胞特异性的GCaMP6s钙指示剂，纤维光度测量实验表明，星形胶质细胞会被尾部束缚（TRT）、足部电击（FS）、开放臂探索、高度应激源、捕食者气味和社会挫败（SD）应激激活。ΔF/F分析表明，在初次接触时，诸如高架平台应激（EPS）等不可预测的刺激会引起星形胶质细胞钙活性最强烈、最快速的变化，而可预测的2,5-二氢-2,4,5-三甲基噻唑啉（TMT）刺激导致的反应最弱，峰值潜伏期更长。在TRT、FS或SD测试中，躯体刺激在重复试验中导致更高的平均钙活性水平和更快的平均峰值潜伏期。与TMT刺激类似，在高架十字迷宫（EPM）测试中，星形胶质细胞钙活性在开放臂探索期间表现出较小的平均幅度变化和最长的峰值潜伏期。此外，在SD测试中，星形胶质细胞钙活性在不同行为状态下表现出不同的变化。我们的研究结果表明，mPFC星形胶质细胞在对各种负面刺激的反应中表现出不同的钙活性模式，表明星形胶质细胞的动态活动可能反映了不同刺激条件下与应激相关的行为状态。
