Standardized and reproducible measurement of decision-making in mice.
Standardized and reproducible measurement of decision-making in mice.
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DOI：
10.7554/elife.63711
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发表时间：
2021-05-20
期刊：
影响因子：
7.7
通讯作者：
Zador AM
中科院分区：
文献类型：
--
作者：
International Brain Laboratory;Aguillon-Rodriguez V;Angelaki D;Bayer H;Bonacchi N;Carandini M;Cazettes F;Chapuis G;Churchland AK;Dan Y;Dewitt E;Faulkner M;Forrest H;Haetzel L;Häusser M;Hofer SB;Hu F;Khanal A;Krasniak C;Laranjeira I;Mainen ZF;Meijer G;Miska NJ;Mrsic-Flogel TD;Murakami M;Noel JP;Pan-Vazquez A;Rossant C;Sanders J;Socha K;Terry R;Urai AE;Vergara H;Wells M;Wilson CJ;Witten IB;Wool LE;Zador AM
科学的进步需要标准化的分析方法，其结果可以在实验室间方便地共享、比较和复制。然而，可重复性一直是神经科学关注的问题，尤其是对小鼠行为的测量。在这里，我们展示了一个标准化的任务来探测老鼠的决策，在多个实验室中产生了可重复的结果。我们采用了一项固定头部小鼠的任务来分析感知和基于价值的决策，我们标准化了训练方案和实验硬件、软件和程序。我们在三个国家的七个实验室训练了140只老鼠，并将500万只老鼠的选择收集到一个公开可用的数据库中。老鼠和实验室的学习速度是不同的，但一旦训练完成，实验室的行为没有显著差异。不同实验室的小鼠采用了类似的依赖视觉刺激、过去的成功和失败以及对刺激先验概率的估计来指导它们的选择。这些结果表明，复杂的小鼠行为可以在多个实验室中重现。他们为可复制的啮齿动物行为建立了标准，并提供了前所未有的数据集和开放获取工具来研究老鼠的决策。更一般地说，它们表明了通过协作开放科学方法实现神经科学可重复性的途径。在科学上，多项研究证实同一结果是至关重要的。因此，研究人员需要知道以前实验的所有细节，以便尽可能准确地实施这些程序。然而，这正在成为神经科学的一个主要问题，因为动物行为研究已被证明是难以复制的，而且大多数实验从未被其他实验室复制。老鼠越来越多地被用来研究决策的神经机制，利用老鼠大脑可用的遗传、成像和生理工具。然而，缺乏标准化的行为分析导致实验室之间的结果不一致。这使得在物理学和遗传学等其他领域取得重大突破的大规模合作变得具有挑战性。为了使这些研究更具可重复性，国际大脑实验室（一个合作研究小组）等人开发了一种标准化的方法来研究小鼠的决策过程，其中包含了该过程的每一步；从训练方案到用于分析数据的软件。在实验中，研究人员向老鼠展示了不同对比度的图像，并要求他们用方向盘指示图像是出现在自己的左边还是右边。然后，每做一次纠正决定，老鼠就会得到一滴糖水。当图像对比度高时，小鼠可以依靠自己的视觉。然而，当图像对比度非常低或为零时，他们需要考虑之前试验的信息，选择最近出现频率较高的一面。该方法在来自三个不同国家的七个实验室中对140只小鼠进行了训练。结果显示，不同的老鼠和实验室的学习速度不同，但一旦训练完成，老鼠的行为一致，依靠视觉刺激或经验以类似的方式指导它们的选择。这些结果表明，小鼠的复杂行为可以在多个实验室中重现，为研究决策提供了前所未有的数据集和开放获取工具。这项工作可以作为其他小组的基础，为神经科学领域的合作铺平道路，帮助解决复杂的研究挑战。
Progress in science requires standardized assays whose results can be readily shared, compared, and reproduced across laboratories. Reproducibility, however, has been a concern in neuroscience, particularly for measurements of mouse behavior. Here, we show that a standardized task to probe decision-making in mice produces reproducible results across multiple laboratories. We adopted a task for head-fixed mice that assays perceptual and value-based decision making, and we standardized training protocol and experimental hardware, software, and procedures. We trained 140 mice across seven laboratories in three countries, and we collected 5 million mouse choices into a publicly available database. Learning speed was variable across mice and laboratories, but once training was complete there were no significant differences in behavior across laboratories. Mice in different laboratories adopted similar reliance on visual stimuli, on past successes and failures, and on estimates of stimulus prior probability to guide their choices. These results reveal that a complex mouse behavior can be reproduced across multiple laboratories. They establish a standard for reproducible rodent behavior, and provide an unprecedented dataset and open-access tools to study decision-making in mice. More generally, they indicate a path toward achieving reproducibility in neuroscience through collaborative open-science approaches. In science, it is of vital importance that multiple studies corroborate the same result. Researchers therefore need to know all the details of previous experiments in order to implement the procedures as exactly as possible. However, this is becoming a major problem in neuroscience, as animal studies of behavior have proven to be hard to reproduce, and most experiments are never replicated by other laboratories. Mice are increasingly being used to study the neural mechanisms of decision making, taking advantage of the genetic, imaging and physiological tools that are available for mouse brains. Yet, the lack of standardized behavioral assays is leading to inconsistent results between laboratories. This makes it challenging to carry out large-scale collaborations which have led to massive breakthroughs in other fields such as physics and genetics. To help make these studies more reproducible, the International Brain Laboratory (a collaborative research group) et al. developed a standardized approach for investigating decision making in mice that incorporates every step of the process; from the training protocol to the software used to analyze the data. In the experiment, mice were shown images with different contrast and had to indicate, using a steering wheel, whether it appeared on their right or left. The mice then received a drop of sugar water for every correction decision. When the image contrast was high, mice could rely on their vision. However, when the image contrast was very low or zero, they needed to consider the information of previous trials and choose the side that had recently appeared more frequently. This method was used to train 140 mice in seven laboratories from three different countries. The results showed that learning speed was different across mice and laboratories, but once training was complete the mice behaved consistently, relying on visual stimuli or experiences to guide their choices in a similar way. These results show that complex behaviors in mice can be reproduced across multiple laboratories, providing an unprecedented dataset and open-access tools for studying decision making. This work could serve as a foundation for other groups, paving the way to a more collaborative approach in the field of neuroscience that could help to tackle complex research challenges.