Astrocyte-Mediated Neuronal Synchronization Properties Revealed by False Gliotransmitter Release.
Astrocyte-Mediated Neuronal Synchronization Properties Revealed by False Gliotransmitter Release.
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DOI：
10.1523/jneurosci.2761-16.2017
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发表时间：
2017-10-11
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影响因子：
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通讯作者：
Parri HR
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作者：
Pirttimaki TM;Sims RE;Saunders G;Antonio SA;Codadu NK;Parri HR
星形胶质细胞自发地释放谷氨酸（Glut）作为胶质递质（GT），导致在邻近神经元中产生突触外NMDAR介导的慢内向电流（SICs），这可以增加局部神经元的兴奋性。然而，有一个赤字，我们的知识的因素，控制自发星形胶质细胞GT释放及其影响的程度。我们发现，在大鼠脑切片中，增加生理递质Glut的供应会在较长时间内增加SICs的频率和信号电荷。这种现象被复制的外源性预暴露的氨基酸D-天冬氨酸（D-Asp）。使用D-Asp作为“假”GT，我们确定了腹侧基底丘脑、CA 1海马和体感皮层中GT释放引起的局部神经元兴奋的程度。通过分析同步神经元NMDAR介导的兴奋，我们发现，在不同的大脑区域的兴奋的性质是保守的。在这三个区域中，星形胶质细胞源性GT释放同步的神经元群的距离>;200 μm。单个神经元参与了一个以上的同步群体，这表明单个神经元可以被一个以上的星形胶质细胞兴奋，并且单个星形胶质细胞可以确定神经元的同步网络。结果证实，星形胶质细胞可以作为兴奋性节点，可以影响神经元在一个显着的范围内，在一些大脑区域。我们的研究结果进一步表明，慢性升高的环境谷氨酸水平可以导致增加GT谷氨酸释放，这可能是相关的一些病理状态。星形胶质细胞自发释放谷氨酸盐（Glut）和其他胶质递质（GT），可以改变神经元的活动。在记录前将脑切片暴露于Glut和D-天冬氨酸（D-Asp）导致GT介导的星形胶质细胞-神经元信号传导频率增加。使用D-Asp，可以研究神经元NMDAR的特异性GT释放的影响。钙成像显示皮质、海马和丘脑中的神经元群同步活动。这些群体的大小是相似的，在所有领域和一些神经元参与了一个以上的同步组。研究结果表明，GT的释放是供应依赖性的，并且信号传导和激活网络的特性在不同脑区之间基本上是保守的。
Astrocytes spontaneously release glutamate (Glut) as a gliotransmitter (GT), resulting in the generation of extrasynaptic NMDAR-mediated slow inward currents (SICs) in neighboring neurons, which can increase local neuronal excitability. However, there is a deficit in our knowledge of the factors that control spontaneous astrocyte GT release and the extent of its influence. We found that, in rat brain slices, increasing the supply of the physiological transmitter Glut increased the frequency and signaling charge of SICs over an extended period. This phenomenon was replicated by exogenous preexposure to the amino acid D-aspartate (D-Asp). Using D-Asp as a “false” GT, we determined the extent of local neuron excitation by GT release in ventrobasal thalamus, CA1 hippocampus, and somatosensory cortex. By analyzing synchronized neuronal NMDAR-mediated excitation, we found that the properties of the excitation were conserved in different brain areas. In the three areas, astrocyte-derived GT release synchronized groups of neurons at distances of >;200 μm. Individual neurons participated in more than one synchronized population, indicating that individual neurons can be excited by more than one astrocyte and that individual astrocytes may determine a neuron's synchronized network. The results confirm that astrocytes can act as excitatory nodes that can influence neurons over a significant range in a number of brain regions. Our findings further suggest that chronic elevation of ambient Glut levels can lead to increased GT Glut release, which may be relevant in some pathological states. SIGNIFICANCE STATEMENT Astrocytes spontaneously release glutamate (Glut) and other gliotransmitters (GTs) that can modify neuronal activity. Exposing brain slices to Glut and D-aspartate (D-Asp) before recording resulted in an increase in frequency of GT-mediated astrocyte–neuron signaling. Using D-Asp, it was possible to investigate the effects of specific GT release at neuronal NMDARs. Calcium imaging showed synchronized activity in groups of neurons in cortex, hippocampus, and thalamus. The size of these populations was similar in all areas and some neurons were involved in more than one synchronous group. The findings show that GT release is supply dependent and that the properties of the signaling and activated networks are largely conserved between different brain areas.