Coupling of activity, metabolism and behaviour across the Drosophila brain

Nature. 2021 May;593(7858):244-248. doi: 10.1038/s41586-021-03497-0. Epub 2021 Apr 28.


Coordinated activity across networks of neurons is a hallmark of both resting and active behavioural states in many species1-5. These global patterns alter energy metabolism over seconds to hours, which underpins the widespread use of oxygen consumption and glucose uptake as proxies of neural activity6,7. However, whether changes in neural activity are causally related to metabolic flux in intact circuits on the timescales associated with behaviour is unclear. Here we combine two-photon microscopy of the fly brain with sensors that enable the simultaneous measurement of neural activity and metabolic flux, across both resting and active behavioural states. We demonstrate that neural activity drives changes in metabolic flux, creating a tight coupling between these signals that can be measured across brain networks. Using local optogenetic perturbation, we demonstrate that even transient increases in neural activity result in rapid and persistent increases in cytosolic ATP, which suggests that neuronal metabolism predictively allocates resources to anticipate the energy demands of future activity. Finally, our studies reveal that the initiation of even minimal behavioural movements causes large-scale changes in the pattern of neural activity and energy metabolism, which reveals a widespread engagement of the brain. As the relationship between neural activity and energy metabolism is probably evolutionarily ancient and highly conserved, our studies provide a critical foundation for using metabolic proxies to capture changes in neural activity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Behavior, Animal*
  • Brain / cytology*
  • Brain / metabolism
  • Brain / physiology*
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / metabolism*
  • Drosophila melanogaster / physiology*
  • Energy Metabolism
  • Female
  • Male
  • Metabolic Networks and Pathways*
  • Neural Pathways
  • Neurons / metabolism*
  • Optogenetics
  • Rest


  • Adenosine Triphosphate