Center for Neuroscience, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea; Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea.
Center for Neuroscience, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea; Department of Neuroscience, Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology, Seoul 02792, Korea.
Cell Rep. 2019 Jul 30;28(5):1154-1166.e5. doi: 10.1016/j.celrep.2019.06.071.
The underlying mechanisms of how positive emotional valence (e.g., pleasure) causes preference of an associated context is poorly understood. Here, we show that activation of astrocytic μ-opioid receptor (MOR) drives conditioned place preference (CPP) by means of specific modulation of astrocytic MOR, an exemplar endogenous Gi protein-coupled receptor (Gi-GPCR), in the CA1 hippocampus. Long-term potentiation (LTP) induced by a subthreshold stimulation with the activation of astrocytic MOR at the Schaffer collateral pathway accounts for the memory acquisition to induce CPP. This astrocytic MOR-mediated LTP induction is dependent on astrocytic glutamate released upon activation of the astrocytic MOR and the consequent activation of the presynaptic mGluR1. The astrocytic MOR-dependent LTP and CPP were recapitulated by a chemogenetic activation of astrocyte-specifically expressed Gi-DREADD hM4Di. Our study reveals that the transduction of inhibitory Gi-signaling into augmented excitatory synaptic transmission through astrocytic glutamate is critical for the acquisition of contextual memory for CPP.
积极情绪效价（例如愉悦）如何导致对相关情境的偏好的潜在机制尚未得到充分理解。在这里，我们表明，通过在 CA1 海马体中特异性调节星形胶质细胞 μ 阿片受体 (MOR)，作为内源性 Gi 蛋白偶联受体 (Gi-GPCR) 的范例，星形胶质细胞 MOR 的激活会导致条件性位置偏好 (CPP)。用星形胶质细胞 MOR 的激活进行亚阈刺激诱导的长时程增强 (LTP) 解释了诱导 CPP 的记忆获取。这种星形胶质细胞 MOR 介导的 LTP 诱导依赖于星形胶质细胞 MOR 激活时释放的星形胶质细胞谷氨酸，以及随后激活的突触前 mGluR1。通过化学遗传激活星形胶质细胞特异性表达的 Gi-DREADD hM4Di 可以重现星形胶质细胞 MOR 依赖性 LTP 和 CPP。我们的研究表明，通过星形胶质细胞谷氨酸将抑制性 Gi 信号转导转化为增强的兴奋性突触传递对于 CPP 的情境记忆获得至关重要。
