Dopamine (DA) is an important neurotransmitter/ neuromodulator throughout the animal kingdom. In humans, dysfunction of the DA system leads to motor, cognitive, and affective disorders. Detailed studies feasible in the genetic model system Drosophila melanogaster permit circuit level definition of pathways responsible for specific behaviors, allow for detailed temporal/spatial control of DA synthesis, and have the potential to uncover novel neural mechanisms relevant to human diseases of DA dysfunction. In this proposal, we study a novel and spontaneous suppression of a subset of dopamine-loss phenotypes. We will use genetic and molecular techniques to identify and characterize the genetic elements responsible for this suppression. Our model is particularly relevant to early stage Parkinson's disease, where a poorly described pathway can partially compensate for decreased DA levels, delaying appearance of symptoms. This proposal focuses on the mechanisms of this compensation.
Dopamine (DA) is an important neurotransmitter/neuromodulator throughout the animal kingdom, and in humans, dysfunction of the DA system leads to motor, cognitive, and affective disorders. Detailed studies feasible in the genetic model system Drosophila melanogaster permit circuit level definition of pathways responsible for specific behaviors, allow for detailed temporal/spatial control of DA synthesis, and have the potential to uncover novel neural mechanisms relevant to human diseases of DA dysfunction. Our studies are particularly relevant to early stage Parkinson's disease, where a poorly described pathway can partially compensate for decreased DA levels.
Cichewicz, Karol; Hirsh, Jay (2018) ShinyR-DAM: a program analyzing Drosophila activity, sleep and circadian rhythms. Commun Biol 1: |
Mead, Brian P; Kim, Namho; Miller, G Wilson et al. (2017) Novel Focused Ultrasound Gene Therapy Approach Noninvasively Restores Dopaminergic Neuron Function in a Rat Parkinson's Disease Model. Nano Lett 17:3533-3542 |
Cichewicz, K; Garren, E J; Adiele, C et al. (2017) A new brain dopamine-deficient Drosophila and its pharmacological and genetic rescue. Genes Brain Behav 16:394-403 |
Niens, Janna; Reh, Fabienne; Çoban, Bü?ra et al. (2017) Dopamine Modulates Serotonin Innervation in the Drosophila Brain. Front Syst Neurosci 11:76 |
Nall, Aleksandra H; Shakhmantsir, Iryna; Cichewicz, Karol et al. (2016) Caffeine promotes wakefulness via dopamine signaling in Drosophila. Sci Rep 6:20938 |
Vinayak, Pooja; Coupar, Jamie; Hughes, S Emile et al. (2013) Exquisite light sensitivity of Drosophila melanogaster cryptochrome. PLoS Genet 9:e1003615 |
Kaun, Karla R; Azanchi, Reza; Maung, Zaw et al. (2011) A Drosophila model for alcohol reward. Nat Neurosci 14:612-9 |
Lee, Pei-Tseng; Lin, Hsuan-Wen; Chang, Yu-Hsuan et al. (2011) Serotonin-mushroom body circuit modulating the formation of anesthesia-resistant memory in Drosophila. Proc Natl Acad Sci U S A 108:13794-9 |
Riemensperger, Thomas; Isabel, Guillaume; Coulom, Hélène et al. (2011) Behavioral consequences of dopamine deficiency in the Drosophila central nervous system. Proc Natl Acad Sci U S A 108:834-9 |
Hirsh, Jay; Riemensperger, Thomas; Coulom, Helene et al. (2010) Roles of dopamine in circadian rhythmicity and extreme light sensitivity of circadian entrainment. Curr Biol 20:209-14 |