A window into the nervous system of the fruit fly

A cultured Drosophila melanogaster fruit fly (foreground) interacts with an intact fly (in background). Credit: Alan Herzog (EPFL)

Scientists at EPFL have developed an implantation technique that allows unprecedented visual access to the “spinal cord” of the fruit fly, Drosophila melanogaster. This work could lead to breakthroughs in the fields of neuroscience, artificial intelligence, and bio-inspired robotics.

Understanding the biological control of motors requires the ability to record nervous activity While the animals behave, says Professor Pavan Ramdia from the School of Life Sciences at EPFL. “We have a billion neurons in the human spinal cord – and it’s a huge system – and we can’t manipulate neurons in a human the way we can in animals. The fruit fly, the fruit fly, is a very small organism where one can genetically manipulate and visualize the activity of motor circuits almost entirely in the animals that behave.”

For years, Ramdya’s research has focused on digitally recapitulating the principles underlying fruit fly motor control. In 2019, his group Publish DeepFly3D, a motion-capture software based on deep learning that uses multiple camera views to determine the 3D limb movements of behaving flies. 2021 Ramdia team LiftPose3D revealed, a method of recreating 3D animals from 2D images taken from a single camera. These efforts were supplemented by its publication in 2022 NeuroMechFlythe first morphologically accurate digital “twin” of the fruit fly.

But there are always more challenges ahead, particularly in this field that lies at the interplay of biology, neuroscience, computer science and robotics. The goal is not just to map and understand an organism’s nervous system – an ambitious task in itself – but also to discover how to develop biology-inspired robots that are as agile as flies.

“The obstacle we had before this work was that we were only able to record the motor circuits for a short period before the animal’s health deteriorated,” Ramdia says.

Therefore, Ramdya collaborated with Professor Salman Sakar in the School of Engineering at EPFL to develop tools to monitor Drosophila neural activity for longer periods of time, up to the insect’s entire lifespan. This project was led by Laura Hermans, PhD. The student who was supervised by Ramdia and Saqr.






Credit: Federal Polytechnic School of Lausanne

Window on the ventral nerve

“We have developed precision-engineered devices that provide optical access to an animal’s ventral nerve cord,” Hermann says, referring to the equivalent of a fly’s spinal cord. “Then we surgically implanted these devices in the chest of the fly,” she continues. “One of these devices, an implant, allows us to move the fly’s organs aside to expose the ventral nerve cord below. We then close the rib cage with a micro-fabricated transparent window. Once we have flies with these devices, we can record the fly’s behavior as well as its neural activity across a wide range of experiments over long periods of time.”

The purpose of all these tools is to allow scientists to observe an individual animal over long periods of time. They can now perform experiments that do not exceed a few hours and can even cover the entire life of a fly. “For example, we can study how an animal’s biology adapts during disease development,” Hermanns says. “We can also study changes in neural circuit activity and structure during aging. The ventral nerve cord of the fly is ideal because it hosts the animal’s motor circuits, allowing us to study how locomotion develops over time or after injury.”

planting

“As engineers, we crave such well-defined technical challenges,” says Salman Sakar. “Pavan’s group developed a dissection technique to remove organs from the fly that block the field of view and visualize the ventral nerve cord. However, flies can only survive for a few hours after surgery. We were convinced that the implant had to be placed inside the thorax. There are similar techniques for organ visualization. We were inspired by these solutions and started thinking about miniaturization.”

Prototypes attempted to meet the challenge of safely moving the fly’s organs and keeping them aside to expose the ventral nerve cord, while still allowing the flies to survive surgery.

A window into the nervous system of the fruit fly

The surgical procedure in which the new V-shaped implant is inserted into the thorax of Drosophila to allow visual access to the ventral nerve cord. Credit: Laura Hermans (EPFL)

“For this challenge, you need someone who can approach a problem from a life sciences and engineering perspective, and this highlights the importance of [Hermans] Murat [Kaynak] work,” says Sakar.

The early implants were solid, and very few flies survived the procedure. trying to improve Survival rates Not sacrificing imaging quality was a challenge that took many iterations in the design. In the end, the winner was a simple but effective prototype: a V-compatible implant that could safely move the fly’s organs aside, expose the ventral cord, and allow researchers to close the opening on the cuticle with a “window-coded thoracic tape,” which allows them to observe the ventral nerve cord And conduct measurements of neural activity while the fly continues its daily life.

“Given the differences from animal to animal in anatomy, we had to find a safe and adaptable solution,” Sakar says. “Our implant meets this particular need. Along with the development of tissue micromanipulation tools and a 3D nanoprinting-compatible stage for the installation the animals During frequent imaging sessions, we present a complete, versatile toolkit for neuroscience research. “

open road

The achievement is an example of the open, interdisciplinary research typical of EPFL. “From day one we are very open to sharing technology,” says Sakar. “The idea here is to quickly deploy the tools and methods so that we can facilitate both the further development of the technology and the discovery process that it presents in many areas of research. A number of groups, I think, want to explore our technology.”

“By studying the fly, we believe that understanding something relatively simple can lay the foundation for understanding more complex organisms,” Ramdia says. When you learn math, don’t dive into it linear algebra; You learn how to add and subtract first. In addition, for robots, it would be great to understand how a “simple” insect works.

The team’s next step is to use their new methodology to unravel the mechanisms that control Drosophila locomotion. “Biological systems are really unique compared to synthetic systems in that they can dynamically modulate, for example, the excitability of neurons or the strength of synapses,” Ramdia adds. ‘So we understand what makes biological systems Very agile, you should be able to observe this dynamic. In our case, we would like to look at how, for example, the motor systems respond over the life of the animal to old age or during recovery after injury. “

The current study was published in Nature Communications.


New technology reveals limb control in flies – and possibly robots


more information:
Laura Hermans et al, Micro-engineered devices enable long-term imaging of the ventral nerve cord in adult Drosophila behaviour, Nature Communications (2022). DOI: 10.1038 / s41467-022-32571-y

the quote: A Window on the Nervous System of the Drosophila (2022, September 13) Retrieved September 13, 2022 from

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