Motor Behavior Mediated by Continuously Generated Dopaminergic Neurons in the Zebrafish Hypothalamus Recovers after Cell Ablation

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.