Calcium dynamics regulating the timing of decision-making in C. elegans.
Calcium dynamics regulating the timing of decision-making in C. elegans.
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DOI：
10.7554/elife.21629
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发表时间：
2017-05-23
期刊：
影响因子：
7.7
通讯作者：
Kimura KD
中科院分区：
文献类型：
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作者：
Tanimoto Y;Yamazoe-Umemoto A;Fujita K;Kawazoe Y;Miyanishi Y;Yamazaki SJ;Fei X;Busch KE;Gengyo-Ando K;Nakai J;Iino Y;Iwasaki Y;Hashimoto K;Kimura KD
大脑以不同的时间来调节行为反应。在这里，我们调查的细胞和分子机制的决策在秀丽隐杆线虫嗅觉导航的时间。我们发现，基于气味浓度的微妙变化，动物似乎从多次试验中选择适当的迁移方向作为行为决策的一种形式。通过视觉生理学，数学和遗传分析的神经活动下的虚拟气味梯度，我们进一步发现，气味浓度信息的时间整合的决定，通过逐渐增加的细胞内钙离子浓度（[Ca 2 +]i），这发生在一对嗅觉神经元的L型电压门控钙通道。相反，对于反射样行为反应，[Ca 2 +]i通过一对伤害性神经元中的多种类型的钙通道迅速增加。因此，神经元反应的时间是由钙通道的细胞类型依赖性参与决定的，这可以作为决策的细胞基础。DOI：http://dx.doi.org/10.7554/eLife.21629.001动物利用来自环境的信息来做决定，比如去哪里，吃什么，和谁交配。这些信息可能是变化的或令人困惑的，当感官信息清晰时，决策可能会很快，而当感官线索混乱时，决策可能会慢一些。科学家们经常在猴子和啮齿动物身上研究这种决策，但很难确定确切的决策机制，因为这些动物的大脑中有数亿个神经元。在神经元较少的简单生物体中，研究决策机制可能更容易。一种叫做秀丽隐杆线虫的小蛔虫就是这样一种生物，它只有302个神经元。这些蠕虫避免有毒气味，当它们发现气味时，首先四处游荡，然后逃跑。大约80%的时间，蠕虫会朝着正确的方向逃跑，以逃避恶臭。然而，目前尚不清楚蠕虫如何决定向哪个方向逃跑。现在，Tanimoto，Yamazoe-Umemoto等人表明，蠕虫通过数学计算气味浓度的信息来选择移动的方向。在实验中，机器人显微镜同时测量神经活动和蠕虫的行为，同时呈现气味。具体地，测量神经元中的钙的量。实验表明，当蠕虫游荡以确定向哪个方向逃离时，神经元中的钙含量与气味浓度随时间变化的程度成正比。实验表明，动物使用一种称为积分的数学过程来计算气味浓度随时间的变化，当总量达到一定阈值时，动物成功地离开了来源。Tanimoto，Yamazoe-Umemoto等人也鉴定了能够进行这些计算的基因。更复杂的动物也会做出类似的计算，在做出决定时会考虑到环境随时间的变化。未来的实验需要确定更复杂的动物是否也使用与C相同的机制。以及是否是同一个基因负责。DOI：http://dx.doi.org/10.7554/eLife.21629.002网站
Brains regulate behavioral responses with distinct timings. Here we investigate the cellular and molecular mechanisms underlying the timing of decision-making during olfactory navigation in Caenorhabditis elegans. We find that, based on subtle changes in odor concentrations, the animals appear to choose the appropriate migratory direction from multiple trials as a form of behavioral decision-making. Through optophysiological, mathematical and genetic analyses of neural activity under virtual odor gradients, we further find that odor concentration information is temporally integrated for a decision by a gradual increase in intracellular calcium concentration ([Ca2+]i), which occurs via L-type voltage-gated calcium channels in a pair of olfactory neurons. In contrast, for a reflex-like behavioral response, [Ca2+]i rapidly increases via multiple types of calcium channels in a pair of nociceptive neurons. Thus, the timing of neuronal responses is determined by cell type-dependent involvement of calcium channels, which may serve as a cellular basis for decision-making. DOI: http://dx.doi.org/10.7554/eLife.21629.001 Animals use information from their environment to make decisions, like where to go, what to eat, and with whom to mate. This information may be changing or confusing, and decisions may be quick when the sensory information is clear, or slower when the sensory clues are muddled. Scientists often study this kind of decision-making in monkeys and rodents, but it can be hard to pinpoint the exact decision-making mechanisms because these animals have hundreds of millions neurons in their brains. Studying the mechanisms that underlie decision-making can be easier in a simpler organism with fewer neurons. A tiny roundworm called Caenorhabditis elegans is one such creature, with only 302 neurons. These worms avoid noxious odors, by first wandering around when they detect the odor, and then fleeing. About 80% of the time the worms flee in the correct direction to escape the foul smell. However, it was not clear how the worms decided which direction to flee. Now, Tanimoto, Yamazoe-Umemoto et al. show that the worms choose which direction to move by mathematically calculating information about odor concentrations. In the experiments, a robotic microscope simultaneously measured nerve activity and the worm’s behavior while an odor was presented. Specifically, the amount of calcium in the neurons was measured. The experiments showed that when the worms were wandering to determine which direction to flee the amount of calcium in the neurons changed in proportion to how much the concentration of the odor changed overtime. The experiments suggest that the animals use a mathematical process called integration to add up the changes in the concentration of the odor over time, and when the total reaches a certain threshold the animal successfully moves away from the source. Tanimoto, Yamazoe-Umemoto et al. also identified the gene that enables these calculations. More complicated animals make similar calculations that take into account environmental changes over time when making a decision. Future experiments are needed to determine if more complex animals also use the same mechanism as C. elegans, and whether the same gene is responsible. DOI: http://dx.doi.org/10.7554/eLife.21629.002