Edmond and Lily Safra Center for Brain Sciences (ELSC), The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
ELSC Vector Core Facility, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Cell. 2018 Jun 28;174(1):59-71.e14. doi: 10.1016/j.cell.2018.05.002. Epub 2018 May 24.
Astrocytes respond to neuronal activity and were shown to be necessary for plasticity and memory. To test whether astrocytic activity is also sufficient to generate synaptic potentiation and enhance memory, we expressed the Gq-coupled receptor hM3Dq in CA1 astrocytes, allowing their activation by a designer drug. We discovered that astrocytic activation is not only necessary for synaptic plasticity, but also sufficient to induce NMDA-dependent de novo long-term potentiation in the hippocampus that persisted after astrocytic activation ceased. In vivo, astrocytic activation enhanced memory allocation; i.e., it increased neuronal activity in a task-specific way only when coupled with learning, but not in home-caged mice. Furthermore, astrocytic activation using either a chemogenetic or an optogenetic tool during acquisition resulted in memory recall enhancement on the following day. Conversely, directly increasing neuronal activity resulted in dramatic memory impairment. Our findings that astrocytes induce plasticity and enhance memory may have important clinical implications for cognitive augmentation treatments.
星形胶质细胞对神经元活动作出反应，被证明对可塑性和记忆至关重要。为了测试星形胶质细胞活动是否足以产生突触增强并增强记忆，我们在 CA1 星形胶质细胞中表达了与 Gq 偶联的受体 hM3Dq，使其能够被一种设计药物激活。我们发现，星形胶质细胞的激活不仅是突触可塑性所必需的，而且足以诱导海马体中的 NMDA 依赖性新的长期增强，这种增强在星形胶质细胞激活停止后仍然存在。在体内，星形胶质细胞的激活增强了记忆分配；也就是说，只有在与学习相结合时，它才会以特定于任务的方式增加神经元活动，而不是在家庭笼养的小鼠中。此外，在获得过程中使用化学遗传学或光遗传学工具激活星形胶质细胞会导致第二天记忆回忆增强。相反，直接增加神经元活动会导致记忆严重受损。我们的发现表明，星形胶质细胞诱导可塑性并增强记忆，这可能对认知增强治疗具有重要的临床意义。
