A day in the life of a larval zebrafish. Characterization and Modeling of Behavioral Dynamics and Interoceptive Homeostasis

项目1 在恒河的家中，斑马鱼面临着特定的挑战，这些挑战与环境不同， 进化了。在一个典型的一天，一个斑马鱼幼虫将不得不导航移动的水流，并防止被席卷 进入未知的领域，它可能必须避免在过度拥挤的浅滩缺氧和干燥，它可能会在身体上 被困在死胡同里，它需要寻找和捕猎潜在的难以捉摸的猎物。它的行为策略， 外感受性和内感受性，在决定其在这种环境中的进化适应性方面发挥着重要作用。 受到斑马鱼在自然界中发现的这些挑战的优雅和通用性的启发，我们设计了 在受控实验室环境下模拟此类行为学相关条件的一系列行为测定，以及 这让我们能够提取计算算法。例如，我们已经表明，鱼类执行时间 在相干点视动反射（cdOMR）1的背景下，对噪声刺激进行积分，我们发现它们计算 空间积分沿着他们的横向线，以估计速度梯度的上下文中的rheotaxis2，他们沉默 在游泳过程中自我诱导和预期传入的体感流信号，从而保护他们敏感的头发 细胞从这些大扰动3.在这里，我们建议扩展这些正在进行的分析，并添加额外的行为 同时传递潜在冲突的感觉输入，并且动物被迫 在互斥的电机输出之间做出决定。 为了超越这些快速的算法计算，为了明确地参与内部的自主调节， 我们将用各种令人厌恶的条件来挑战动物，包括暴露在缺氧等威胁中， 或高盐4，或当动物的运动是徒劳的，他们放弃时发生的挫折5，6。该第二组 行为挑战和相关分析需要在我们的建模框架中包含更长的时间常数。 除了更新动物的行为输出外，它们还涉及心脏反应的调节， 这使得它们非常适合于研究自主和内感受状态的调节。 我们的总体目标是通过设计概率算法来建立动物行为的综合模型， 运动和心脏对各种感觉输入的反应。我们包括心脏（在某些情况下包括呼吸） 活动，因为这些作为内部状态的指标，否则必须推测为大脑的隐藏修饰符 功能，但也因为他们提供了一个读出如何感觉输入影响内部稳态。 为了使我们的实验方法适应每个特定行为测定所需的分辨率和控制，我们 我在各种空间尺度的竞技场中设计了几种开放和封闭的循环配置，以及完全沉浸式的 虚拟现实设置为栓系准备。我们希望这些研究将促进我们对算法的理解 将环境和内部环境与行为输出联系起来， 在经典的外感受性意义上，作为完整动物8所做的总运动，以及 内感受水平9.

Project 1 At home in the Ganges, zebrafish are faced with specific challenges that are idiosyncratic to the environment they evolved in. On a typical day, a larval zebrafish will have to navigate moving water currents and prevent getting swept into unknown territory, it might have to avoid hypoxia and desiccation in overcrowded shallows, it could get physically trapped in cul-de-sacs, and it will need to find and hunt potentially elusive prey. Its behavioral strategies, both exteroceptive and interoceptive, play major roles in determining its evolutionary fitness in this environment. Inspired by the elegance and generality of the solutions a zebrafish finds to these challenges in nature, we have designed a series of behavioral assays that emulate such ethologically relevant conditions under controlled laboratory settings, and which allow us to extract the computational algorithms. For example, we have shown that fish perform temporal integration over noisy stimuli in the context of the coherent-dot optomotor reflex (cdOMR)1, we found that they calculate spatial integrals along their lateral line to estimate velocity gradients in the context of rheotaxis2, and that they silence self-induced and expected incoming somatosensory flow signals during swims and thereby protect their sensitive hair cells from these large perturbations3. Here, we propose to extend these ongoing analyses and to add additional behavioral paradigms where potentially conflicting sensory inputs are delivered simultaneously, and where the animal is forced to make decisions between mutually exclusive motor outputs. To go beyond these fast algorithmic computations, and in order to explicitly engage the autonomic regulation of internal states, we will challenge the animal with a variety of aversive conditions, including exposure to threats such as hypoxia or high salt4, or the frustration that occurs when an animal's motion is futile and they give up5,6. This second set of behavioral challenges and related analyses requires the inclusion of longer time constants into our modeling framework. They also are known to involve modulation of cardiac responses in addition to updating the animal's behavioral output, which makes them well suited to investigate the regulation of autonomic and interoceptive states. Our overall goal is to create comprehensive models of animal behavior by devising probabilistic algorithms that model motor and cardiac responses to a variety of sensory inputs. We are including cardiac (and in some cases respiratory) activity because these serve as indicators of internal states7 that must otherwise be surmised as hidden modifiers of brain function, but also because they offer a readout for how sensory input affects internal homeostasis. In order to adapt our experimental approach to the resolution and control required by each specific behavioral assay, we have designed several open and closed loop configurations in arenas of various spatial scales, as well as fully immersive virtual reality settings for tethered preparations. We hope these studies will advance our understanding of the algorithms that relate and interconnect environmental and internal context to behavioral output, where we define behavioral output operationally both in the classical - exteroceptive - sense as the total movements made by the intact animal 8, as well as at the interoceptive level9.