Nuriya Mutsuo, Takeuchi Miyabi, Yasui Masato
Department of Pharmacology, School of Medicine, Keio University, Shinjuku, Tokyo, 160-8582, Japan; Keio Advanced Research Center for Water Biology and Medicine, Keio University, Shinjuku, Tokyo, 160-8582, Japan; Graduate School of Environment and Information Sciences, Yokohama National University, Yokohama, Kanagawa, 240-8501, Japan.
Department of Pharmacology, School of Medicine, Keio University, Shinjuku, Tokyo, 160-8582, Japan.
Biochem Biophys Res Commun. 2017 Jan 29;483(1):732-738. doi: 10.1016/j.bbrc.2016.12.073. Epub 2016 Dec 11.
Norepinephrine (NE) levels in the cerebral cortex are regulated in two modes; the brain state is correlated with slow changes in background NE concentration, while salient stimuli induce transient NE spikes. Previous studies have revealed their diverse neuromodulatory actions; however, the modulatory role of NE on astrocytic activity has been poorly characterized thus far. In this study, we evaluated the modulatory action of background NE on astrocytic responses to subsequent stimuli, using two-photon calcium imaging of acute murine cortical brain slices. We find that subthreshold background NE significantly augments calcium responses to subsequent pulsed NE stimulation in astrocytes. This priming effect is independent of neuronal activity and is mediated by the activation of β-adrenoceptors and the downstream cAMP pathway. These results indicate that background NE primes astrocytes for subsequent calcium responses to NE stimulation and suggest a novel gliomodulatory role for brain state-dependent background NE in the cerebral cortex.
大脑皮层中的去甲肾上腺素（NE）水平通过两种模式进行调节；大脑状态与背景NE浓度的缓慢变化相关，而显著刺激会诱发NE的瞬时峰值。先前的研究已经揭示了它们多样的神经调节作用；然而，迄今为止，NE对星形胶质细胞活性的调节作用仍未得到充分表征。在本研究中，我们使用急性小鼠皮质脑片的双光子钙成像技术，评估了背景NE对星形胶质细胞对后续刺激反应的调节作用。我们发现，阈下背景NE显著增强了星形胶质细胞对后续脉冲式NE刺激的钙反应。这种预激发效应独立于神经元活动，并由β-肾上腺素能受体的激活和下游cAMP途径介导。这些结果表明，背景NE使星形胶质细胞对后续NE刺激产生钙反应做好准备，并提示大脑状态依赖性背景NE在大脑皮层中具有一种新的胶质调节作用。
