Animals have evolved specialized neural circuits to defend themselves from pain-and injurycausing stimuli. Using a combination of optical, behavioral and genetic approaches in the larval zebrafish, we describe a novel role for hypothalamic oxytocin (OXT) neurons in the processing of noxious stimuli. In vivo imaging reveals that a large and distributed fraction of zebrafish OXT Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:
Summary
Postembryonic neurogenesis has been observed in several regions of the vertebrate brain, including the dentate gyrus and rostral migratory stream in mammals, and is required for normal behavior [1–3]. Recently the hypothalamus has also been shown to undergo continuous neurogenesis as a way to mediate energy balance [4–10]. As the hypothalamus regulates multiple functional outputs, it is likely that additional behaviors may be affected by postembryonic neurogenesis in this brain structure. Here, we have identified a progenitor population in the zebrafish hypothalamus that continuously generates neurons that express tyrosine hydroxylase 2 (th2). We develop and use novel transgenic tools to characterize the lineage of th2+ cells and demonstrate that they are dopaminergic. Through genetic ablation and optogenetic activation we then show that th2+ neurons modulate the initiation of swimming behavior in zebrafish larvae. Finally we find that the generation of new th2+ neurons following ablation correlates with restoration of normal behavior. This work thus identifies for the first time a population of dopaminergic neurons that regulates motor behavior capable of functional recovery.
Tools for genetically-determined visualization of synaptic circuits and interactions are necessary to build connectomics of the vertebrate brain and to screen synaptic properties in neurological disease models. Here we develop a transgenic FingR (fibronectin intrabodies generated by mRNA display) technology for monitoring synapses in live zebrafish. We demonstrate FingR labeling of defined excitatory and inhibitory synapses, and show FingR applicability for dissecting synapse dynamics in normal and disease states. Using our system we show that chronic hypoxia, associated with neurological defects in preterm birth, affects dopaminergic neuron synapse number depending on the developmental timing of hypoxia.
The rapid adoption of the larval zebrafish as a systems neuroscience model has been driven largely by its small size and optical transparency, which enable the use of imaging and optogenetics techniques to record and manipulate activity throughout the brain.Unfortunately, larval fish lack the mature behavioral repertoire of adults and so a number of learning phenomena and social behaviors cannot be investigated in these animals.Here we establish the pedomorphic fish species Danionella translucida as a laboratory model that overcomes this limitation. Adult Danionella possess the size and optical transparency of late-larval zebrafish, which we exploit to image deep within the brains of a behaviorally mature animals using two-photon microscopy. The close phylogenetic relationship between Danionella and zebrafish enabled us to use existing reagents and techniques for transgenesis, and zebrafish-derived enhancer elements drove transgene expression in Danionella with their intended specificities. In a behavioral assay for socially-reinforced place preference, interactions between fish were found to be positively reinforcing and dependent on gender, demonstrating the power of this species for studies of learning and memory as well as social behavior. The establishment of Danionella's behavioral, molecular, and optical tractability provides a unique opportunity for researchers seeking to understand the relationship between circuits and adult-onset behaviors at a whole-brain level.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.