Watson School of Biological Sciences and.
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724.
J Neurosci. 2018 Nov 21;38(47):10143-10155. doi: 10.1523/JNEUROSCI.3478-17.2018. Epub 2018 Oct 15.
The ability to manipulate neural activity with precision is an asset in uncovering neural circuits for decision-making. Diverse tools for manipulating neurons are available for mice, but their feasibility remains unclear, especially when decisions require accumulating visual evidence. For example, whether mice' decisions reflect leaky accumulation is unknown, as are the relevant/irrelevant factors that influence decisions. Further, causal circuits for visual evidence accumulation are poorly understood. To address this, we measured decisions in mice judging the fluctuating rate of a flash sequence. An initial analysis (>500,000 trials, 29 male and female mice) demonstrated that information throughout the 1000 ms trial influenced choice, with early information most influential. This suggests that information persists in neural circuits for ∼1000 ms with minimal accumulation leak. Next, in a subset of animals, we probed strategy more extensively and found that although animals were influenced by stimulus rate, they were unable to entirely suppress the influence of stimulus brightness. Finally, we identified anteromedial (AM) visual area via retinotopic mapping and optogenetically inhibited it using JAWS. Light activation biased choices in both injected and uninjected animals, demonstrating that light alone influences behavior. By varying stimulus-response contingency while holding stimulated hemisphere constant, we surmounted this obstacle to demonstrate that AM suppression biases decisions. By leveraging a large dataset to quantitatively characterize decision-making behavior, we establish mice as suitable for neural circuit manipulation studies. Further, by demonstrating that mice accumulate visual evidence, we demonstrate that this strategy for reducing uncertainty in decision-making is used by animals with diverse visual systems. To connect behaviors to their underlying neural mechanism, a deep understanding of behavioral strategy is needed. This understanding is incomplete for mice. To surmount this, we measured the outcome of >500,000 decisions made by 29 mice trained to judge visual stimuli and performed behavioral/optogenetic manipulations in smaller subsets. Our analyses offer new insights into mice' decision-making strategies and compares them with those of other species. We then disrupted neural activity in a candidate neural structure and examined the effect on decisions. Our findings establish mice as suitable for visual accumulation of evidence decisions. Further, the results highlight similarities in decision-making strategies across very different species.
精准操控神经活动的能力对于揭示决策的神经回路是非常有帮助的。有多种用于操控神经元的工具可用于小鼠，但它们的可行性尚不清楚，特别是当决策需要积累视觉证据时。例如，小鼠的决策是否反映了渗漏性积累尚不清楚，影响决策的相关/不相关因素也不清楚。此外，视觉证据积累的因果回路也知之甚少。为了解决这个问题，我们在判断闪烁序列波动率的小鼠中测量了决策。最初的分析（超过 50 万次试验，29 只雄性和雌性小鼠）表明，整个 1000 毫秒试验中的信息都会影响选择，早期信息最具影响力。这表明信息在神经回路中持续存在约 1000 毫秒，且累积泄漏最小。接下来，在一小部分动物中，我们更广泛地探测了策略，发现尽管动物受到刺激率的影响，但它们无法完全抑制刺激亮度的影响。最后，我们通过视网膜映射确定了前内侧（AM）视觉区域，并通过 JAWS 对其进行光遗传抑制。光激活使注射和未注射动物的选择产生偏差，表明光本身会影响行为。通过在保持刺激半球不变的情况下改变刺激-反应的关联性，我们克服了这个障碍，证明 AM 抑制会使决策产生偏差。通过利用一个大型数据集来定量描述决策行为，我们证明小鼠适合进行神经回路操作研究。此外，通过证明小鼠积累视觉证据，我们证明了这种在决策中减少不确定性的策略被具有不同视觉系统的动物使用。为了将行为与其潜在的神经机制联系起来，需要对行为策略有深入的了解。对于老鼠来说，这种理解并不完整。为了克服这一障碍，我们测量了 29 只接受过判断视觉刺激训练的老鼠做出的超过 50 万次决策的结果，并在更小的亚组中进行了行为/光遗传操作。我们的分析为小鼠的决策策略提供了新的见解，并将其与其他物种进行了比较。然后，我们破坏了候选神经结构中的神经活动，并检查了其对决策的影响。我们的发现表明，小鼠适合进行视觉证据积累决策。此外，结果突出了不同物种在决策策略上的相似性。
