A Genetic Toolkit for Dissecting Dopamine Circuit Function in Drosophila
Tingting Xie,
Margaret C.W. Ho,
Qili Liu,
Wakako Horiuchi,
Chun-Chieh Lin,
Darya Task,
Haojiang Luan,
Benjamin H. White,
Christopher J. Potter,
Mark N. Wu
Affiliations
Tingting Xie
School of Life Sciences, Peking University, Beijing 100871, China; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Margaret C.W. Ho
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Qili Liu
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Wakako Horiuchi
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Chun-Chieh Lin
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Darya Task
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Haojiang Luan
Laboratory of Molecular Biology, National Institute of Mental Health, NIH, Bethesda, MD 20892, USA
Benjamin H. White
Laboratory of Molecular Biology, National Institute of Mental Health, NIH, Bethesda, MD 20892, USA
Christopher J. Potter
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Mark N. Wu
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Summary: The neuromodulator dopamine (DA) plays a key role in motor control, motivated behaviors, and higher-order cognitive processes. Dissecting how these DA neural networks tune the activity of local neural circuits to regulate behavior requires tools for manipulating small groups of DA neurons. To address this need, we assembled a genetic toolkit that allows for an exquisite level of control over the DA neural network in Drosophila. To further refine targeting of specific DA neurons, we also created reagents that allow for the conversion of any existing GAL4 line into Split GAL4 or GAL80 lines. We demonstrated how this toolkit can be used with recently developed computational methods to rapidly generate additional reagents for manipulating small subsets or individual DA neurons. Finally, we used the toolkit to reveal a dynamic interaction between a small subset of DA neurons and rearing conditions in a social space behavioral assay. : The rapid analysis of how dopaminergic circuits regulate behavior is limited by the genetic tools available to target and manipulate small numbers of these neurons. Xie et al. present genetic tools in Drosophila that allow rational targeting of sparse dopaminergic neuronal subsets and selective knockdown of dopamine signaling. Keywords: dopamine, genetics, behavior, neural circuits, neuromodulation, Drosophila
