Genetic and neural mechanisms underlying emerging social behavior in zebrafish

斑马鱼新兴社会行为的遗传和神经机制 我们的目标是了解群体中新兴的集体行为，例如鱼群聚集和成群结队。 我们的方法是剖析斑马鱼的基本感觉运动转变，我们认为这在斑马鱼中发挥着重要作用 在解释新兴的社会互动方面发挥着重要作用。我们已经确定了两个简单且描述良好的 反射行为：1）视运动反射（OMR），鱼随着整个场运动刺激而游动， 2) 物体引起的重新定向反应（OER），其中鱼转身离开或转向移动的物体，具体取决于 关于物体的大小和运动。我们在初步建模研究中表明，一个实现 虚拟代理中这两个简单的“运动原语”可以解释新兴社交的很大一部分 成年鱼的行为。将我们的研究集中在这两种简单的反射上的一个引人注目的优势是 它们在 7 天大的幼虫中强烈表达，这有助于详细和定量的行为 分析相关的视觉运动转换，以及对其潜在神经回路的剖析。 我们提案中的一个关键要素是突变斑马鱼的产生，我们已经证明它们表现出微妙的变化 但在成年阶段有独特的社会行为表型。我们发现，即使在幼虫阶段， 在出现强烈的群聚和成群行为之前，这些突变体已经表现出行为 OMR 和 OER 背景下的表型，这些表型偏差可以预测 后来成人在学校教育和浅滩上出现了差异。我们的中心目标之一是剖析 突变体神经回路的具体变化导致了这些行为改变 表型。神经表型的一些变化可能会体现在整体大脑结构的水平上，但是 许多可能会破坏微电路——无论是在细胞身份还是突触连接层面—— 是胚胎中简单行为和成人中更复杂行为的基础。值得注意的是，我们已经 生成了现实的电路模型，形成了关于底层神经网络的特定假设 野生型动物中的 OMR 和 OER，并且这些模型很容易调整以识别和限制 突变动物中发生变化的特定潜在变量。这种调整后的模型可以作为理想的先验 以及在全脑功能成像实验中测试的具体假设。最后是身份识别 突变动物的详细神经表型的解剖位置、神经元细胞命运和 突触特异性将促进这些解剖学和生理学变化与特定细胞命运的联系 和分子途径。我们在描述和建模大脑范围的神经回路方面正在进行并行的努力 斑马鱼（在 U19 团队研究大脑回路计划的框架内）将使我们能够缩小范围 突变体中所有这些可观察到的神经表型中哪些与以下因素有关并与之存在因果关系 行为变化背后的特定神经变化。

Genetic and neural mechanisms underlying emerging social behavior in zebrafish Our goal is to understand emerging collective behaviors of groups, such as schooling and shoaling in fish. Our approach is to dissect basic sensorimotor transformations in the zebrafish, which we believe play a fundamental role in explaining emerging social interactions. We have identified two simple and well described reflexive behaviors: 1) the optomotor reflex (OMR), where fish swim along with whole field motion stimuli and 2) object evoked re-orienting responses (OER) where fish turn away or towards moving objects, depending on the object’s size and movement. We have shown in preliminary modeling studies that an implementation of these two simple “motor primitives” in virtual agents can explain a significant fraction of the emerging social behaviors in adult fish. A compelling advantage of focusing our studies on these two simple reflexes is that they are robustly expressed in 7 day old larvae, which facilitates a detailed and quantitative behavioral analysis of the related visuomotor transformation, as well as a dissection of their underlying neural circuitry. A critical element in our proposal is the generation of mutant zebrafish that we have shown to display subtle but distinctive social behavioral phenotypes at the adult stage. We found that, even in the larval stage, and prior to onset of robust schooling and shoaling behaviors, these mutants already reveal behavioral phenotypes in the context of the OMR and OER, and that these phenotypical deviations are predictive of the later emerging differences in schooling and shoaling in adults. One of our central goals is the dissection of the specific changes in neural circuitry in the mutants that are responsible for these altered behavioral phenotypes. Some such changes in neural phenotype may manifest at the level of global brain structures, but many are likely to disrupt micro-circuits - either at the level of cellular identities or synaptic connectivity - that underlie both simple behavior in the embryo and more complex behaviors in the adult. Notably, we already have generated realistic circuit models that form specific hypotheses about the neural networks underlying the OMR and OER in wild-type animals, and these models are readily adjusted to identify and constrain the specific latent variables that are changed in the mutant animals. Such adjusted models serve as ideal priors and specific hypotheses to be tested in brain wide functional imaging experiments. Lastly, the identification of detailed neural phenotypes in mutant animals in terms of anatomical location, neuronal cell fate and synaptic specificity will facilitate linkage of these anatomical and physiological changes to specific cell fates and molecular pathways. Our parallel ongoing efforts in describing and modelling brain wide neural circuits in zebrafish (within the framework of the U19 Team-Research BRAIN Circuits program) will allow us to narrow down which of all these observable neural phenotypes in the mutants are responsible and causally related to the specific neural changes that underlie the changes in behavior.