The Heart and the Mind: An Integrative Approach to Brain-Body Interactions in the Zebrafish

心脏和思想：斑马鱼脑体相互作用的综合方法

• 批准号: 10686975
• 负责人: Florian Engert
• 金额: $ 371.9万
• 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/10686975
• 关键词: Adaptive Behaviors; Address; Algorithms; Animals; Articulation; Autonomic ganglion; Autonomic nervous system; Behavior; Behavior Control; Behavioral; Behavioral Assay; Behavioral Model; Biological Assay; Brain; Cardiac; Cardiovascular system; Cells; Central Nervous System; Classification; Computational algorithm; Cues; Data; Data Set; Dissection; Elements; Environment; Event; Fatigue; Feedback; Fishes; Frequencies; Functional Imaging; Generations; Goals; Heart; Homeostasis; Hunger; Image; Interneurons; Interoception; Knowledge; Light; Machine Learning; Maps; Measurement; Measures; Mediating; Methods; Mind; Modeling; Monitor; Motivation; Motor; Motor Neurons; Nervous System; Neural Interconnection; Neurons; Organ; Oxygen; Pathway interactions; Physiological; Physiology; Positioning Attribute; Process; Protocols documentation; Reflex action; Regulation; Reporting; Research; Resolution; Resources; Rewards; Role; Sensory; Series; Synapses; System; Testing; Time; Validation; Work; Zebrafish; automated segmentation; behavioral response; cell type; connectome; connectome data; dynamic system; experience; experimental study; flexibility; guided inquiry; imaging study; interest; mind body interaction; mind control; neural; neural circuit; neural model; novel; optogenetics; patch clamp; receptor; respiratory; response

The heart and the mind: an integrative approach to brain-body interactions in the zebrafish Our current U19 has focused primarily on Exteroception, which can be defined as the accumulated sensory experience originating from events in the outside world. However, all neural computation takes place in the context of the body, which is subject to the dynamics of hunger, fatigue, motivation and diurnal cycles. The information that reaches the brain from the organs and receptors inside of the body, summarized under the umbrella term of Interoception, is therefore overlaid onto exteroceptive computations. This adds behavioral variability to any animal task, from changing vigor to altering valence of rewards to vetoing responses altogether. To better understand such embodied computation, we will first incorporate cardiac and respiratory variables that dynamically report basic internal states to our standard behavioral classification methods, and we will include detailed characterization and modeling of the autonomic and intracardiac nervous system in our functional imaging studies. Finally, as a critical resource for the description and validation of the generated neural circuit models, we will create a complete body-and-brain connectome of the larval zebrafish. This research plan is aligned with the three levels of understanding articulated by David Marr more than thirty years ago, who emphasized the importance of considering Evolutionary Principles, Algorithmic Representation and Hardware Implementation as a unified and interconnected approach for understanding the brain. Following this framework, we first try to isolate aspects of fish behavior that are adapted to their native environment and context. We next use a variety of controlled behavioral assays to extract the algorithmic rules that govern the dynamics of modular sensorimotor transformations, and that are augmented by knowledge about internal state changes as reflected by observed modulation of cardiac and respiratory activity. To characterize the hardware implementation of these explicit and latent behavioral algorithms, we propose to first measure cellular activity using brain-wide functional light imaging of the central, the autonomic and the intracardiac nervous systems (CNS, ANS and ICNS). We next will use these comprehensive datasets to generate realistic circuit models of the observed dynamics. These models will then guide a series of circuit dissection experiments, such as optogenetic perturbations of specific cell types, targeted patch-clamp physiology and sparse connectomics tracing, allowing us to validate, extend, and constrain our models. We note that this approach also affords us the opportunity to discover new circuit elements and circuit motifs, and novel ways to implement computational algorithms by the brain. Another extension of our current U19 is the addition of a dynamical modeling framework for these behaviors, where animals can interact flexibly with the environment, and where we consider multiple time scales of interaction. We believe that this constitutes a different and perhaps ethologically more relevant approach when compared to the highly constrained, simplified and repetitive challenges we used before. Further, this framework is well suited in characterizing the continuous process of cardiac control and its interaction with behavioral modulation.

心与思想：大脑与身体相互作用的综合方法 斑马鱼 我们目前的U19主要关注外感，可以定义为积累的感官经验 源于外部世界的事件。然而，所有神经计算都发生在身体的背景下， 它受饥饿、疲劳、动机和昼夜周期的动态影响。到达大脑的信息 来自身体内部的器官和受体，总结在内感受的总称下，因此是 叠加到外感受计算上。这增加了任何动物任务的行为变异性，从改变活力到 改变奖励的效价以完全否决反应。 为了更好地理解这种具体计算，我们首先将合并心脏和呼吸变量 动态地向我们的标准行为分类方法报告基本的内部状态，我们将包括详细的内部状态 我们的功能成像研究中自主神经和心内神经系统的表征和建模。 最后，作为描述和验证生成的神经电路模型的关键资源，我们将创建一个 斑马鱼幼虫的完整身体和大脑连接组。 该研究计划与三十多年前大卫·马尔阐述的三个层次的理解相一致， 他强调了考虑进化原理、算法表示和硬件的重要性 作为理解大脑的统一且相互关联的方法来实施。遵循这个框架，我们首先 尝试分离出适合其原生环境和背景的鱼类行为的各个方面。接下来我们使用各种 受控行为分析，提取控制模块化感觉运动动力学的算法规则 变换，并且通过观察到的调制所反映的内部状态变化的知识来增强 心脏和呼吸活动。表征这些显性和潜在行为的硬件实现 算法中，我们建议首先使用中枢的全脑功能光成像来测量细胞活动 自主神经和心内神经系统（CNS、ANS 和 ICNS）。接下来我们将使用这些综合数据集 生成所观察动态的真实电路模型。这些模型随后将指导一系列电路剖析 实验，例如特定细胞类型的光遗传学扰动、靶向膜片钳生理学和稀疏 连接组学追踪，使我们能够验证、扩展和约束我们的模型。我们注意到这种方法还为我们提供了 有机会发现新的电路元件和电路图案，以及实现计算的新方法 大脑的算法。 我们当前 U19 的另一个扩展是为这些行为添加动态建模框架，其中 动物可以灵活地与环境互动，并且我们考虑互动的多个时间尺度。我们相信 与高度相关的方法相比，这构成了一种不同的、也许在行为学上更相关的方法 我们之前使用过的受限、简化和重复的挑战。此外，该框架非常适合表征 心脏控制的连续过程及其与行为调节的相互作用。