Neuron-glia signaling in developing retina mediated by neurotransmitter spillover.
Neuron-glia signaling in developing retina mediated by neurotransmitter spillover.
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DOI：
10.7554/elife.09590
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发表时间：
2015-08-14
期刊：
影响因子：
7.7
通讯作者：
Feller MB
中科院分区：
文献类型：
--
作者：
Rosa JM;Bos R;Sack GS;Fortuny C;Agarwal A;Bergles DE;Flannery JG;Feller MB
神经元-胶质细胞相互作用在神经回路的成熟中起着关键作用;然而，对发育中的CNS中介导其通信的途径知之甚少。我们研究了发育中的视网膜中的神经胶质细胞信号，在那里我们证明了视网膜波可靠地诱导Müller胶质细胞（MC）中的钙瞬变。在胆碱能波期间，MC钙瞬变被毒蕈碱型乙酰胆碱受体拮抗剂阻断，而在谷氨酸能波期间，MC钙瞬变被离子型谷氨酸受体拮抗剂抑制，表明MC的反应性变化与用于支持视网膜波的神经递质相匹配。使用光学谷氨酸传感器，我们表明，MC钙瞬变的下降是由于谷氨酸达到MC的量减少。总之，这些研究表明，神经元和MCs在视网膜成熟的关键时期表现出相关的活动，这是由视网膜突触的神经递质溢出实现的。http://dx.doi.org/10.7554/eLife.09590.001眼睛后部的一个结构被称为视网膜，对视力至关重要。当光线照射到视网膜时，被称为神经元的细胞产生电信号，导致被称为神经递质的化学物质的释放。当这些化学物质到达邻近的神经元时，在该细胞中产生相应的电信号。通过这种方式，我们所看到的信息最终会传递到大脑。视网膜还含有非神经元的细胞，如米勒神经胶质细胞。这些细胞跨越视网膜的厚度，并且似乎很好地与视网膜中所有不同类型的神经元相互作用。其他类型的神经胶质细胞帮助大脑中的神经回路发育，但目前尚不清楚穆勒细胞是否在发育中的视网膜中发挥同样的作用。新生小鼠直到出生后大约两周才睁开眼睛，在此期间，它们的视网膜继续发育。视网膜神经元在这一时期已经很活跃，并自发地产生周期性的电活动，以波的形式传播到发育中的视网膜。现在，Rosa，Bos等人表明，在新生小鼠中，这些波也会触发Müller细胞内钙离子浓度的短暂或“瞬时”增加。米勒细胞的反应方式取决于在波动过程中释放的神经递质。在小鼠睁开眼睛前几天，Müller细胞中的钙瞬变数量急剧减少。与此同时，神经元继续自发地释放一种叫做谷氨酸的特殊神经递质。Rosa，Bos等人使用了一种传感器，可以显示在发育中的视网膜中发现谷氨酸的位置。这表明，随着视网膜成熟，钙瞬变的减少是由于到达Müller细胞的谷氨酸减少。这些发现表明，在视网膜发育的关键时期，Müller细胞参与视网膜中观察到的自发电活动。下一个挑战是确定这种神经元-胶质细胞信号传导如何帮助视网膜成熟。DOI：http://dx.doi.org/10.7554/eLife.09590.002网站
Neuron-glia interactions play a critical role in the maturation of neural circuits; however, little is known about the pathways that mediate their communication in the developing CNS. We investigated neuron-glia signaling in the developing retina, where we demonstrate that retinal waves reliably induce calcium transients in Müller glial cells (MCs). During cholinergic waves, MC calcium transients were blocked by muscarinic acetylcholine receptor antagonists, whereas during glutamatergic waves, MC calcium transients were inhibited by ionotropic glutamate receptor antagonists, indicating that the responsiveness of MCs changes to match the neurotransmitter used to support retinal waves. Using an optical glutamate sensor we show that the decline in MC calcium transients is caused by a reduction in the amount of glutamate reaching MCs. Together, these studies indicate that neurons and MCs exhibit correlated activity during a critical period of retinal maturation that is enabled by neurotransmitter spillover from retinal synapses. DOI: http://dx.doi.org/10.7554/eLife.09590.001 A structure at the back of the eye known as the retina is essential for vision. When light hits the retina, cells called neurons produce electrical signals that lead to the release of chemicals known as neurotransmitters. When these chemicals reach a neighboring neuron, a corresponding electrical signal is produced in this cell. In this way, information about what we can see is ultimately transmitted to the brain. The retina also contains cells that are not neurons, such as Müller glial cells. These cells span the thickness of the retina, and appear well placed to interact with all of the different types of neuron in the retina. Other types of glial cells help the neural circuits in the brain to develop, but it is not clear whether Müller cells perform the same role in the developing retina. Newborn mice do not open their eyes until around two weeks after they are born, during which time their retina continues to develop. The retinal neurons are already active throughout this period, and spontaneously generate periodic bursts of electrical activity that spreads across the developing retina in waves. Now, Rosa, Bos et al. show that in newborn mice, these waves also trigger brief, or ‘transient’, increases in the concentration of calcium ions inside Müller cells. Exactly how the Müller cells respond depends on which neurotransmitters are released during waves. A few days before the mice open their eyes, the number of calcium transients in Müller cells decreases sharply. At the same time, neurons continue to spontaneously release waves of one particular neurotransmitter called glutamate. Rosa, Bos et al. used a sensor that showed where glutamate is found in the developing retina. This revealed that the decrease in calcium transients as the retina matures is due to less glutamate reaching the Müller cells. These findings reveal that Müller cells are involved in the spontaneous electrical activity seen in the retina during a critical period of retinal development. The next challenge is to determine how this neuronal-glial cell signaling helps the retina to mature. DOI: http://dx.doi.org/10.7554/eLife.09590.002