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

• Published in: Current biology 2016-01, Vol.26 (2), p.263-269
• Main Authors: McPherson, Adam D., Barrios, Joshua P., Luks-Morgan, Sasha J., Manfredi, John P., Bonkowsky, Joshua L., Douglass, Adam D., Dorsky, Richard I.
• Format: Article
• Language: English
• Subjects: Animals; Animals, Genetically Modified; Behavior, Animal - physiology; Dopamine - metabolism; Dopaminergic Neurons - metabolism; Hypothalamus - metabolism; Motor Activity - physiology; Neurogenesis - physiology; Zebrafish - genetics; Zebrafish - metabolism; Zebrafish Proteins - metabolism
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2015.11.064

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. [Display omitted] •Dopaminergic th2+ neurons in the zebrafish hypothalamus arise from Dlx+ precursors•th2+ neurons are continuously generated into adulthood and recover after ablation•Swim frequency is decreased by ablation and increased by activation of th2+ neurons•Recovery of th2+ neurons correlates with restoration of swim behavior McPherson et al. show that dopaminergic th2+ neurons in zebrafish are continuously generated into adulthood and use opto- and pharmacogenetic techniques to demonstrate their function in swimming. They find that recovery of th2+ neurons after ablation correlates with the restoration of normal swimming behavior.