Astrocytes perform various supporting functions, including ion buffering, metabolic supplying and neurotransmitter clearance. They can also sense neuronal activity owing to the presence of specific receptors for neurotransmitters. In turn, astrocytes can regulate synaptic activity through the release of gliotransmitters. Evidence has shown that astrocytes are very sensitive to the locus coeruleus (LC) afferents. However, little is known about how LC neuromodulatory norepinephrine (NE) modulates synaptic transmission through astrocytic activity. In mouse dentate gyrus (DG), we demonstrated an increase in the frequency of miniature excitatory postsynaptic currents (mEPSC) in response to NE, which required the release of glutamate from astrocytes. The rise in glutamate release probability is likely due to the activation of presynaptic GluN2B-containing NMDA receptors. Moreover, we showed that the activation of NE signaling in DG is necessary for the formation of contextual learning memory. Thus, NE signaling activation during fear conditioning training contributed to enduring changes in the frequency of mEPSC in DG. Our results strongly support the physiological neuromodulatory role of NE signaling, which is derived from activation of astrocytes.

星形胶质细胞执行各种支持功能，包括离子缓冲、代谢供应和神经递质清除。由于存在特定的神经递质受体，它们还可以感知神经元活动。反过来，星形胶质细胞可以通过释放胶质递质来调节突触活动。有证据表明，星形胶质细胞对蓝斑 (LC) 传入神经非常敏感。然而，关于 LC 神经调节去甲肾上腺素 (NE) 如何通过星形胶质细胞活动调节突触传递知之甚少。在小鼠齿状回 (DG) 中，我们证明了响应 NE 的微型兴奋性突触后电流 (mEPSC) 的频率增加，这需要从星形胶质细胞中释放谷氨酸。谷氨酸释放概率的增加可能是由于突触前含有 GluN2B 的 NMDA 受体的激活。此外，我们表明 DG 中 NE 信号的激活对于形成情境学习记忆是必要的。因此，恐惧条件反射训练期间的 NE 信号激活有助于 DG 中 mEPSC 频率的持久变化。我们的结果强烈支持 NE 信号的生理神经调节作用，它源自星形胶质细胞的激活。