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Image of a fly brain. Copyright: Dr. Anatoli Ender



Looking into the brain of the fruit fly

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Image of a fly brain. Individual nerve cells are marked via specific gating (magenta), nerve cell connections are shown in green. Copyrights: Dr. Anatoli Ender
Image of a fly brain. Individual nerve cells are marked via specific gating (magenta), nerve cell connections are shown in green. Copyrights: Dr. Anatoli Ender

With around 100,000 nerve cells, the fruit fly has a rather small brain. But that also has certain advantages. The team led by neurophysiologist Prof. Dr. David Owald is using Drosophila melanogaster to find answers to one of the great mysteries of humankind: How are we controlled? An ERC Consolidator Grant is now funding the work with around two and a half million euros.

When beeing hungry, we eat; when beeing tired, we go to sleep; and when a reward beckons, we adjust our behavior accordingly. Things get more complex when two competing needs collide. Hunger and fatigue, for example, or need for sleep versus need to ward off danger. How does our brain decide then? And how do we even make decisions to do one thing and not to do another?

The neurophysiologist and behavioral scientist Prof. Dr. David Owald and his research group "Behavioral and Physiological Neurogenetics" at the Institute of Neurophysiology at the Charité are working on such fundamental questions of behavioral control. The experiments, however, do not take place with human subjects, but with a tiny insect that we often find on rotting fruit or on the residue in a wine glass: the fruit fly. Even though Drosophila melanogaster has only an estimated 100,000 neurons and humans have about 100 billion, the little animal has become a popular genetic model in behavioral biology, making it possible to avoid using more sophisticated organisms in these fields for certain questions.

"Want to know how we are controlled"
"We want to know how we are controlled, we would like to understand these complex things," says David Owald, who is also a member of the NeuroCure Cluster of Excellence. At the moment, he says, far too little is known about how exactly networks of neurons and filtering mechanisms in the brain lead to certain patterns of behavior and influence decisions or even diseases such as depression.

There is a simple reason why Owald and his colleagues are using fruit flies, of all things, to solve big puzzles: On the one hand, certain basic needs and the associated behavioral patterns overlap with humans. On the other hand, genetically modified fruit flies offer researchers the chance to activate individual neurons and watch their behavior change. This would be much more difficult in mammals.

Sleep, for example, can be studied very well in the fly by switching on known sleep neurons to make the fly sleep, says David Owald. Hunger or associative memory, for example between a scent and the stored memory of it, could also be studied well in the insect. "We are interested in the question which activity patterns underlie basal behavior and how brain structures change as a result of a sugar reward, for example, and how this then in turn affects memory and behavior," emphasizes the behavioral researcher.

Reward is a very big topic in behavioral research. In extreme cases, reward stimuli can even lead to "addiction-like behavior" in fruit flies. Other research teams had already shown such a loss of control for alcohol, underscoring both the parallels between the two species and laying the groundwork for addiction research. "Of course, we're a long way from humans, and you have to abstract the results," says David Owald. Still, he says, it's "striking how dopaminergic neurons that signal reward in us do the same in fruit flies." 

Active neurons begin to light up 
The researchers can observe how active a brain cell or neuron cluster is at any given moment using fluorescent dyes under special microscopes. When activity is high, the neurons begin to glow - and vice versa. Even the control of entire network ensembles can be measured with the special methods.

The researchers hope to find out about addiction mechanisms and other misguided processes such as epilepsies and depression. After all, around 75 percent of the disease-relevant genes in humans are also found in fruit flies. These genes don't necessarily always have the same function, Owald says, so care must be taken. "But if we want to understand the basal function of the protein encoded by a gene now - we can take a good look at that in the fly - whether it's in the context of epilepsy or addiction, for example." 

The "Simple Minds" project, on the other hand, is initially about something very healthy, namely sleep. Together with an international team, Owald is investigating the hypothesis that sensory information is specifically filtered to enable sleep or falling asleep and staying asleep. These filters could, for example, ensure that parents wake up at night when their baby cries, but sleep through the night when the birds start chirping in the morning - at least that is the assumption. First, the research team wants to investigate the influence of light on sleep behavior. 

Rhythm is it 
"We believe that rhythmic network activity ensures that only certain sensory stimuli are allowed through and that these rhythmic states alternate, so that we enter a state of self-referral that can only be broken by a strong or just significant stimulus," Owald explains the hypothesis.

Since sleep has become a problem for many people due to light pollution and stress, the project also has a current background. In preliminary work, the researchers had already discovered that the rhythmic frequencies found in flies are very similar to those found in humans. The researchers are now trying to understand what happens at the neuronal level in the "simple minds. The results cannot be transferred 1:1 to humans, says David Owald, but they can be transferred in a slightly different form. "The basic principles are likely to be very similar, and that's what we're concerned with in this project."

The "Simple Minds" project will receive about two and a half million euros in funding from an ERC Consolidator Grant over the next five years. The grant is awarded by the European Research Council (ERC) under the Horizon Europe framework program for "groundbreaking research."

(Text: Beatrice Hamberger)


Owald Group

Institute of Neurophysiology 


Charité 3R

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