Bittersweet Secrets of the Fly Brain
Scientists map neural circuitry controlling behavioral responses to sugar
The sense of taste carries evolutionary benefits key to survival. A sweet taste, for instance, signals energy-dense nutrients important to animals foraging for food — including humans. A bitter taste may warn of a toxic substance.
“We use our sense of taste to decide what to eat and how much to eat,” says Anita Devineni, a neuroscientist and assistant professor in Emory University’s Department of Biology.
Despite the importance of taste, little is known about how taste cues spark the firing of cells across a brain and evoke a variety of behavioral responses. Devineni is exploring this mystery by mapping the neural circuitry for the taste system of the fruit fly, Drosophila melanogaster.
Tinier than a poppy seed, the fruit fly brain contains around 140,000 neurons.
“That’s 1,000 fewer neurons than a mouse brain and a million times fewer than a human brain,” Devineni explains, making the fly brain a simple starting point for studying general mechanistic principles of cognition.
An image of the fruit fly brain shows neural pathways associated with taste in green. (Image created by Anita Devineni from FlyWire data).
An image of the fruit fly brain shows neural pathways associated with taste in green. (Image created by Anita Devineni from FlyWire data).
Compared to the incredible complexity of its cognitive powers, the human brain’s basic biology appears relatively straightforward.
“The brain is just an organ like any other organ in your body,” Devineni says. “It’s made up of neurons that are cells like any other cells — lipid membranes containing proteins, DNA and other molecules. What makes a brain cell different from a skin cell or a lung cell is that a brain cell fires. Firing means that sodium ions flow in and out of the cell. Everything that you do, from thinking to talking to walking, is a result of patterns of neurons firing. How could this be?”
Mysteries of how the brain works fired Anita Devineni's passion while she was still an undergraduate, inspiring her to focus her career on studying neural processing.
Mysteries of how the brain works fired Anita Devineni's passion while she was still an undergraduate, inspiring her to focus her career on studying neural processing.
The latest paper from the Devineni Lab, recently published in Cell Reports, shows the overlap and divergence of “sweet” brain circuits that signal fruit flies to hit the brakes, begin eating, opt to spend time in those “sweet spots” and associate sweet taste with other signals in the environment.
The researchers also revealed the neural circuitry at play when a fly encounters equal amounts of sweet and bitter tastes. “The bitter taste wins, overriding the sweet,” Devineni says. “In fact, the flies run away.”
First author of the paper is Ruby Jacobs, a research technician in Devineni’s lab. Co-authors include Emory undergraduate students Crystal Wang (who graduated in May 2024), Lam Nguyen and Penny Wang; Emory graduate student Trinity Pruitt; former Emory research specialist Fiorella Lozada-Perdomo; Julia Deere (Rockefeller University); and Hannah Liphart (Columbia University).
Fruit flies have served as an important laboratory organism for more than 100 years. In 1910, Thomas Hunt Morgan discovered the mutant gene of a white-eyed male fruit fly and for the first time tied a specific gene to a particular chromosome.
In 2000, the genome of the fruit fly, made up of around 13,700 genes, became one of the first to be fully sequenced.
Research on fruit flies continues to lead to important discoveries — including ones involving nervous system development and function — as tools and techniques keep advancing.
Devineni’s lab, for instance, employs molecular studies, functional imaging, behavior experiments, computational modeling and optogenetics — a technique that allows researchers to shine a light on a fruit fly to activate specific neurons.
Go on a "fly through" through the fruit fly brain via a video produced by FlyWire Princeton.
The most recent technological advancement in the study of fruit flies is a “connectome,” or map of all 140,000 neurons of the fruit fly brain and the wiring between them. Published in October by FlyWire, a consortium of dozens of research institutions led by Princeton University, it is the first complete map of a complex brain.
Devineni, who was not a member of the FlyWire consortium, relies on its data to plan experiments and develop simulations.
In an editorial she wrote for Nature, Devineni describes how the fruit fly connectome “provided an invaluable resource for researchers to trace neural circuits, generate hypotheses about their function and create circuit models that are grounded in actual connectivity. Analogies to whole-genome sequencing are apt: neither the genome nor the connectome alone can solve the problem, but they provide a structural foundation from which functional insights can arise.”
More of the fruit fly brain appears dedicated to vision than any other sense. That helps the insects to respond quickly to visual cues as they fly.
Smell helps them determine where to touch down. “Taste starts as soon as they land because flies have taste cells, along with touch cells, in their legs,” Devineni says.
Using the FlyWire connectome data, other investigators had mapped out the neural circuitry that causes a fruit fly to extend its straw-like “tongue,” or proboscis, in response to sugar.
For the Cell Reports paper, Devineni’s lab wanted to expand on this work by tracing the neural circuitry involved in a range of behaviors induced by a sweet taste.
The researchers conducted experiments on fruit flies genetically modified to express light-sensitive ion channels in particular cell types associated with sugar. Shining a red light on these modified fruit flies gives the scientists a kind of remote-control power over their brains, tricking them into thinking that they are tasting sugar, even though they are in an empty, plastic container.
A video camera recorded the behaviors of the flies as they reacted to the red-light stimulus.
“When they first ‘taste’ sugar their velocity goes to zero,” Devineni says. “At first we thought the video was freezing because they stopped so quickly.”
The researchers identified which neurons, when activated, caused the flies to stop.
They also confirmed which neurons, when activated, prompted a fly to extend its proboscis to try to suck up the phantom sugar.
The researchers found that fruit flies spent more time in areas when certain sugar neurons were activated.
The results showed that the neural circuitry for stopping, proboscis extension and hanging out in the “sweet spots” occurred in lower-level brain areas and that the circuitry for all three behaviors partially overlapped.
When flies were conditioned to expect sugar in the presence of a particular odor, they later showed an attraction for that odor even when their sugar neurons were not activated. However, none of the sugar neurons that evoked stopping, proboscis extension or spatial preference could evoke this learned response.
Graphic by the Devineni Lab.
Graphic by the Devineni Lab.
“We showed how lower-order ‘sugar neurons’ in the fly brain multi-task to evoke more than one behavior when it comes to generally processing sensory information,” Devineni says. “Learning, however, appears to be mediated by a completely different, higher-order circuit.”
Experiments, combined with simulations using the fly brain connectome data, also showed how a bitter taste overrides the sugar circuity that causes stopping, instead causing the flies to run away.
“This study not only provides new insight into sweet taste processing, but also reveals more general principles of how neural circuits are organized,” Devineni says. “Ultimately, we’re trying to understand how the processing of information in the brain works at the level of individual cells.”
Story by Carol Clark.
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