Astrocytes play a key role in brain homeostasis and functions such as memory. Specifically, astrocytes express multiple receptors that transduce signals via the second messenger cAMP. However, the involvement of astrocytic cAMP in animal behavior and the underlying glial–neuronal interactions remains largely unknown. Here, we show that an increase in astrocytic cAMP is sufficient to induce synaptic plasticity and modulate memory. We developed a method to increase astrocytic cAMP levels in vivo using photoactivated adenylyl cyclase and found that increased cAMP in hippocampal astrocytes at different time points facilitated memory formation but interrupted memory retention via NMDA receptor–dependent plasticity. Furthermore, we found that the cAMP-induced modulation of memory was mediated by the astrocyte–neuron lactate shuttle. Thus, our study unveils a role of astrocytic cAMP in brain function by providing a tool to modulate astrocytic cAMP in vivo.

星形胶质细胞在大脑稳态和记忆等功能中起着关键作用。具体而言，星形胶质细胞表达多种受体，这些受体通过第二信使 cAMP 转导信号。然而，星形细胞 cAMP 在动物行为中的参与以及潜在的神经胶质 - 神经元相互作用仍然很大程度上未知。在这里，我们表明星形细胞 cAMP 的增加足以诱导突触可塑性和调节记忆。我们开发了一种使用光活化腺苷酸环化酶在体内增加星形胶质细胞 cAMP 水平的方法，发现在不同时间点海马星形胶质细胞中 cAMP 的增加促进了记忆的形成，但通过 NMDA 受体依赖性可塑性中断了记忆保留。此外，我们发现 cAMP 诱导的记忆调节是由星形胶质细胞 - 神经元乳酸穿梭介导的。因此，