Genetic and neural mechanisms underlying emerging social behavior in zebrafish

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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.