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

斑马鱼幼虫生命中的一天。

• 批准号: 10686986
• 负责人: MARK C FISHMAN
• 金额: $ 67.2万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-25 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10686986
• 关键词: Adult; Affect; Algorithms; Animal Behavior; Animal Model; Animals; Behavior; Behavioral; Behavioral Assay; Behavioral Model; Behavioral Paradigm; Biological Assay; Brain; Cardiac; Cardiovascular system; Complex; Computational algorithm; Crowding; Decision Making; Desiccation; Environment; Exposure to; Face; Fishes; Frequencies; Frustration; Generations; Goals; Hair Cells; Hand; Heart; Heart Rate; Home; Homeostasis; Hypoxia; Laboratories; Larva; Life; Light; Maps; Measurement; Mind; Modality; Modeling; Monitor; Motion; Motor; Motor output; Movement; Nature; Neural Interconnection; Neurons; Oral cavity; Output; Oxygen; Pathway interactions; Pattern; Pectoral; Performance; Phase; Physiological; Play; Preparation; Proxy; Reflex action; Regulation; Research; Resolution; Role; Sensory; Series; Signal Transduction; Sodium Chloride; Statistical Models; Stimulus; Swimming; System; Testing; Time; Update; Variant; Vertebrates; Water; Zebrafish; connectome; design; environmental change; experimental study; fitness; lateral line; mind body interaction; motor behavior; multimodality; multisensory; neural; neural circuit; prevent; respiratory; response; sensorimotor system; sensory input; sensory integration; somatosensory; virtual reality; virtual reality environment

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.

项目1 在恒河的家中，斑马鱼面临着它们所处环境特有的特殊挑战 进化到。在典型的一天，幼虫斑马鱼将不得不在流动的水流中航行，防止被冲刷。 进入未知领域，它可能不得不避免过度拥挤的浅水区的缺氧和干燥，它可能会 被困在死胡同里，它将需要寻找和猎杀潜在的难以捉摸的猎物。它的行为策略，无论是 外部感觉和内部感觉，在决定其在这种环境中的进化适合性方面发挥着重要作用。 受斑马鱼对自然界这些挑战的解决方案的优雅和一般性的启发，我们设计了 在受控实验室环境下模拟这种行为学相关条件的一系列行为分析，以及 这使我们能够提取计算算法。例如，我们已经证明了鱼执行时间 在相干点视运动反射(CdOMR)1的背景下，我们发现它们计算 沿它们的侧线的空间积分，以在流变性的背景下估计速度梯度2，并且它们是沉默的 游泳过程中自我感应和预期传入的体感流动信号，从而保护他们敏感的头发 来自这些大扰动的细胞3。在这里，我们建议扩展这些正在进行的分析，并添加其他行为 潜在的相互冲突的感觉输入同时传递的范例，以及动物被迫 在互不相容的电机输出之间做出决定。 超越了这些快速的算法计算，为了明确地参与内部自主调节 在美国，我们将在各种令人厌恶的条件下挑战这种动物，包括暴露在缺氧等威胁下 或者高盐度，或者当动物的运动是徒劳的，它们放弃了5，6的时候发生的挫败感。 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量。 众所周知，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神经和感觉间状态的调节。 我们的总体目标是通过设计概率算法来创建动物行为的全面模型 运动和心脏对各种感觉输入的反应。我们包括心脏(在某些情况下还包括呼吸系统) 活动，因为它们是内部状态的指示器，否则就必须被推测为大脑的隐藏修饰物 功能，但也是因为它们提供了一个读数，说明感觉输入如何影响内部动态平衡。 为了使我们的实验方法适应每个特定行为分析所需的解决和控制，我们 在各种空间尺度的竞技场中设计了几种开环和闭环式配置，以及完全沉浸式的 系留准备的虚拟现实设置。我们希望这些研究将促进我们对算法的理解 它将环境和内部环境与行为输出联系起来并相互连接，其中我们定义了行为输出 在操作上，在经典的外部感觉意义上，如完整的动物8所做的全部动作，以及在 内感水平9。