Genetic and neural mechanisms underlying emerging social behavior in zebrafish

斑马鱼社会行为的遗传和神经机制 我们的目标是了解群体的新兴集体行为，如鱼群聚集和鱼群聚集。 我们的方法是解剖斑马鱼的基本感觉运动转换，我们相信这在斑马鱼的进化过程中起着重要作用。 在解释新兴社会互动中的重要作用。我们已经确定了两个简单的和良好的描述 反射行为：1）视动反射（OMR），其中鱼沿着全场运动刺激， 2)对象诱发的重定向反应（OER），其中鱼转向远离或朝向移动的对象，这取决于 物体的大小和运动我们已经在初步的建模研究中表明， 这两个简单的“运动原语”在虚拟代理可以解释一个新兴的社会的重要部分， 成年鱼的行为把我们的研究集中在这两个简单的反射上的一个引人注目的优势是， 它们在7日龄幼虫中强烈表达，这有助于详细和定量的行为分析。 分析相关的视觉转换，以及解剖其潜在的神经回路。 在我们的提议中，一个关键因素是突变斑马鱼的产生，我们已经证明， 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， 在开始强大的学校教育和浅水行为之前，这些突变体已经表现出行为 在OMR和OER的背景下，这些表型偏差可以预测 后来出现的差异，在学校和浅水中的成年人。我们的中心目标之一是解剖 突变体中神经回路的特定变化， 表型神经表型中的一些此类变化可能在整体脑结构水平上表现出来， 许多可能会破坏微电路-无论是在细胞身份或突触连接的水平- 是胚胎期简单行为和成年期复杂行为的基础。值得注意的是，我们已经 已经产生了现实的电路模型，形成了关于神经网络的具体假设， 野生型动物的OMR和OER，并且这些模型易于调整以鉴定和限制 在突变动物中发生变化的特定潜在变量。这种调整后的模型作为理想的先验 以及在全脑功能成像实验中测试的特定假设。最后，识别 详细的神经表型突变动物的解剖位置，神经元细胞的命运， 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。我们在描述和模拟大脑神经回路方面的平行持续努力， 斑马鱼（在U19团队研究脑回路计划的框架内）将使我们能够缩小 突变体中所有这些可观察到的神经表型中， 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.