title: Motor Behavior Mediated by Continuously Generated Dopaminergic Neurons in the Zebrafish Hypothalamus Recovers after Cell Ablation.
abstract: 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.
authors.affiliation: Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Adam D
authors.initials: AD
authors.lastname: McPherson
authors.affiliation: Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Joshua P
authors.initials: JP
authors.lastname: Barrios
authors.affiliation: Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Sasha J
authors.initials: SJ
authors.lastname: Luks-Morgan
authors.affiliation: Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Manfredi
authors.affiliation: Department of Pediatrics, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Bonkowsky
authors.affiliation: Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, UT 84112, USA. Electronic address: adam.douglass@neuro.utah.edu.
authors.forename: Adam D
authors.initials: AD
authors.lastname: Douglass
authors.affiliation: Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, UT 84112, USA. Electronic address: richard.dorsky@neuro.utah.edu.
authors.forename: Richard I
authors.initials: RI
authors.lastname: Dorsky
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001522:Behavior, Animal / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism*; D009043:Motor Activity / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology*; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D029961:Zebrafish Proteins; D004298:Dopamine