Careful When You Swat! Latent Binge State Revealed in Drosophila

Published: July 21, 2014

Researchers in the lab of Kristin Scott at the University of California, Berkeley and the Howard Hughes Medical Institute have made an important discovery regarding inhibitory control of feeding using the fruit fly Drosophila melanogaster. A longtime favorite of geneticists and developmental biologists owing to its ease of cultivation, short lifespan, and simple genetic organization; Drosophila has fully entered the realm of behavioral neuroscience. Recent tools such as inducible ion channels to augment or silence neural activity and fluorescent reporters are being combined with classical neuroscience methodology like electrophysiology and pharmacology to ask relevant questions for patients with eating disorders (ED). As EDs universally affect food intake patterns, developing effective treatments for these symptoms requires that clinicians and researchers develop a more cohesive model of the neural circuitry and molecular machinery that are required for the regulation of feeding.

The beginning of their study is a familiar basic science strategy: Test a lot of fly strains using a simple behavioral assay. The Drosophila nervous system is made up of ~100,000 neurons, and they silenced the activity of different combinations of them using 363 distinct transgenic fly stocks. After inhibiting these neurons, they monitored water consumption in immobilized adult flies. Using this approach, they identified six lines that displayed a voracious drinking phenotype. They demonstrated that these “binge” flies lack water satiety and will drink to the point of regurgitation. One of these lines inactivated a unique array of neurons that they chose to characterize further.

Using a classical mosaic approach to narrow down the relevant neurons even further, they determined that either chronic or acute inactivation of 4 neurons known as descending subesophageal neurons (DSOG1) was sufficient to induce the excessive fluid consumption. To determine if inactivation of DSOG neurons produced a selective increase in water intake, they tested whether inactivation of DSOG1 neurons could also produce increased intake of other substances. Surprisingly, inactivation of these neurons resulted in elevated intake of either rewarding (sucrose) or aversive (ethanol) fluids. The results suggested that these neurons control feeding irrespective of gustatory cues that predict taste quality or nutritional state.

To determine how DSOG1 neuron inactivation produces binge-like consumption, the authors monitored foraging and proboscis extension in free feeding flies and observed that DSOG1 inactivation primarily resulted in an increase in proboscis extension that would occur regardless of whether the animals were fed or deprived. Using an interdisciplinary approach including electrophysiology and in vivo calcium imaging, the authors determined that DSOG1 neurons are inhibitory GABAergic interneurons that control the activity of premotor neuronal circuitry that receive gustatory and satiety signals.

So…but these are flies, right? How are these obeservations relevant to humans with bulimia nervosa or binge eating disorder? Many lines of research using rodents have demonstrated that either lesions or exogenous activation of brain areas using electrical and optogenetic stimulation can trigger binge-like food intake. This study, however, is the first to reveal how inhibition of an anatomically defined, discrete population of neurons can trigger binge-like behavior. Of central importance is that these neurons provide constant inhibitory control over a latent, default binge state. The presence of this behavior in flies, in addition to mammals, argues that binge feeding is a behavioral program that is evolutionarily conserved and that layers of inhibitory control are critical to suppress it. Future work in mammals will be critical to identify similar neuronal ensembles that provide inhibition of binge feeding and how the activity of these circuits is altered in behavioral models of binge eating disorder.

photo credit: Johan J.Ingles-Le Nobel via Creative Commons