University of Bordeaux, CNRS, Interdisciplinary Institute for Neuroscience, Bordeaux, France.
Okinawa Institute of Science and Technology Graduate University, Tancha, Onna-son, Okinawa, Japan.
Neuroscience. 2023 Aug 10;525:38-46. doi: 10.1016/j.neuroscience.2023.05.032. Epub 2023 Jun 7.
Astrocytes have been increasingly acknowledged to play active roles in regulating synaptic transmission and plasticity. Through a variety of metabotropic and ionotropic receptors expressed on their surface, astrocytes detect extracellular neurotransmitters, and in turn, release gliotransmitters to modify synaptic strength, while they can also alter neuronal membrane excitability by modulating extracellular ionic milieu. Given the seemingly large repertoire of synaptic modulation, when, where and how astrocytes interact with synapses remain to be fully understood. Previously, we have identified a role for astrocyte NMDA receptor and L-VGCCs signaling in heterosynaptic presynaptic plasticity and promoting the heterogeneity of presynaptic strengths at hippocampal synapses. Here, we have sought to further clarify the mode by which astrocytes regulate presynaptic plasticity by exploiting a reduced culture system to globally evoke NMDA receptor-dependent presynaptic plasticity. Recording from a postsynaptic neuron intracellularly loaded with BAPTA, briefly bath applying NMDA and glycine induces a stable decrease in the rate of spontaneous glutamate release, which requires the presence of astrocytes and the activation of A1 adenosine receptors. Upon preventing astrocyte calcium signaling or blocking L-VGCCs, NMDA + glycine application triggers an increase, rather than a decrease, in the rate of spontaneous glutamate release, thereby shifting the presynaptic plasticity to promote an increase in strength. Our findings point to a crucial and surprising role of astrocytes in controlling the polarity of NMDA receptor and adenosine-dependent presynaptic plasticity. Such a pivotal mechanism unveils the power of astrocytes in regulating computations performed by neural circuits and is expected to profoundly impact cognitive processes.
星形胶质细胞在调节突触传递和可塑性方面的作用越来越受到认可。通过其表面表达的各种代谢型和离子型受体，星形胶质细胞检测细胞外神经递质，并相应地释放神经胶质递质来调节突触强度，同时通过调节细胞外离子环境改变神经元膜的兴奋性。鉴于似乎有大量的突触调节，星形胶质细胞与突触相互作用的时间、地点和方式仍有待充分了解。此前，我们已经确定星形胶质细胞 NMDA 受体和 L-VGCC 信号在异突触突触前可塑性中的作用，并促进海马突触的突触前强度的异质性。在这里，我们试图通过利用全局激发 NMDA 受体依赖性突触前可塑性的简化培养系统，进一步阐明星形胶质细胞调节突触前可塑性的模式。从细胞内负载 BAPTA 的突触后神经元进行记录，短暂浴用 NMDA 和甘氨酸诱导自发谷氨酸释放率的稳定下降，这需要星形胶质细胞的存在和 A1 腺苷受体的激活。在防止星形胶质细胞钙信号或阻断 L-VGCCs 后，NMDA+甘氨酸的应用会触发自发谷氨酸释放率的增加，而不是减少，从而使突触前可塑性向促进强度增加的方向转变。我们的发现指出了星形胶质细胞在控制 NMDA 受体和腺苷依赖性突触前可塑性极性方面的关键和惊人作用。这种关键机制揭示了星形胶质细胞在调节神经回路进行的计算中的强大功能，并有望对认知过程产生深远影响。
