A single dopamine pathway underlies progressive locomotor deficits in a Drosophila model of Parkinson disease.
Expression of the human Parkinson-disease-associated protein α-synuclein in all Drosophila neurons induces progressive locomotor deficits. Here, we identify a group of 15 dopaminergic neurons per hemisphere in the anterior medial region of the brain whose disruption correlates with climbing impairments in this model. These neurons selectively innervate the horizontal β and β' lobes of the mushroom bodies, and their connections to the Kenyon cells are markedly reduced when they express α-synuclein. Using selective mushroom body drivers, we show that blocking or overstimulating neuronal activity in the β' lobe, but not the β or γ lobes, significantly inhibits negative geotaxis behavior. This suggests that modulation of the mushroom body β' lobes by this dopaminergic pathway is specifically required for an efficient control of startle-induced locomotion in flies.
Genetics and Physiopathology of Neurotransmission, Neurobiology Unit, CNRS, ESPCI ParisTech, 10 rue Vauquelin, 75005 Paris, France; Molecular Neurobiology of Behaviour, Johann-Friedrich-Blumenbach Institute, Georg-August-University of Goettingen, Schwann-Schleiden Research Center, Julia-Lermontowa Weg 3, 37077 Goettingen, Germany. Electronic address: triemen@gwdg.de.
Thomas
T
Riemensperger
Abdul-Raouf
AR
Issa
Ulrike
U
Pech
Hélène
H
Coulom
Mỹ-Vân
MV
Nguyễn
Marlène
M
Cassar
Mélanie
M
Jacquet
André
A
Fiala
Serge
S
Birman
D000818:Animals; D030801:Animals, Genetically Modified; D001921:Brain / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000378:metabolism*; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007473:Ion Channels; D008124:Locomotion / Q000235:genetics / Q000502:physiology*; D024521:Mushroom Bodies / Q000294:innervation; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000378:metabolism* / Q000503:physiopathology; D013216:Reflex, Startle / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000378:metabolism; D051844:alpha-Synuclein / Q000096:biosynthesis / Q000235:genetics
D029721:Drosophila Proteins; D007473:Ion Channels; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; C475684:TrpA1 protein, Drosophila; D051844:alpha-Synuclein; D049452:Green Fluorescent Proteins; D004298:Dopamine