A Single Dopamine Pathway Underlies Progressive Locomotor Deficits in a Drosophila Model of Parkinson Disease

Cell Rep. 2013 Nov 27;5(4):952-60. doi: 10.1016/j.celrep.2013.10.032. Epub 2013 Nov 14.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Brain / metabolism
  • Disease Models, Animal*
  • Dopamine / metabolism*
  • Dopaminergic Neurons / metabolism*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / metabolism*
  • Female
  • Green Fluorescent Proteins / genetics
  • Humans
  • Ion Channels
  • Locomotion / genetics
  • Locomotion / physiology*
  • Mushroom Bodies / innervation
  • Oxidative Stress
  • Parkinson Disease / metabolism*
  • Parkinson Disease / physiopathology
  • Reflex, Startle / genetics
  • Reflex, Startle / physiology
  • Signal Transduction
  • TRPA1 Cation Channel
  • TRPC Cation Channels / metabolism
  • alpha-Synuclein / biosynthesis
  • alpha-Synuclein / genetics

Substances

  • Drosophila Proteins
  • Ion Channels
  • TRPA1 Cation Channel
  • TRPC Cation Channels
  • TrpA1 protein, Drosophila
  • alpha-Synuclein
  • Green Fluorescent Proteins
  • Dopamine