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Computer genetic metrics of fly brain reveal sex differences

Computer genetic metrics in the fly brain reveal gender differences

Neurons and Glia cells of the Drosophila larval ventral nerve cord (spinal cord analog). Credit: B. McCabe (EPFL)

Thanks to genetic tools that allow computers to accurately count neurons from microscopy images, EPFL researchers estimate with unprecedented accuracy the number of neurons and other types of neurons. brain cells in fruit fly larvae — and discovered that females have more neurons than males.

Determining the number of brain cells is key to studying the structure and function of the brain. But counting neurons from microscopic images takes time, and the human eye is easily weakened. To overcome this problem, researchers usually slice the brain tissue and then count the number of cells in a section to estimate the total number of neurons in the brain. But these methods are easily mistaken, because they assume that the number of neurons or other cells is the same in the entire brain. Now, EPFL scientists have developed a new method of identifying cells with superior human accuracy and speed in the empty brain of a Drosophila (fruit fly) larva, a important neuroscience model organism.

The results showed fewer neurons and more glia — a type of cells that support and protect neurons — than previously thought. The team also discovered unexpected differences between the male and female larval brains, with females having more neurons than males.

“Right now, scientists are trying to make robots or computers that can solve problems that have traditionally been solved by humans,” said study senior author Brian McCabe, director of the Laboratory of Neural Genetics and Disease. and a Professor at the EPFL School of Life Sciences. “We’re trying to address the computers in the middle by making the problem easier for them to solve.” For example, when neuroscientists look at nerve cells, they mark the entire surface of the cell. However, neurons may have more complex structures: like other cells, they have a circular cell body in which the nucleus and other cell structures are located; but neurons have something that other cells don’t have – intricate protrusions that come from the cell body to carry electrical and chemical signals inside and outside the cell. “It’s very difficult for computers to scale,” McCabe said.

Working on Drosophila larvae, Wei Jiao, a postdoctoral scientist at McCabe lab, and his colleagues used genetic tools to express a fluorescent tag that would only make the nucleus of the neuron ignite. Then, they imaged the brain of the larvae using a sophisticated microscopy technique that allows the researchers to create a 3D image of a sample without damaging it. Finally, the group asked computers to examine and analyze the images under the microscope. “In these images, the neuron is just a dot, and machine vision doesn’t have to look for complex 3D shapes — it just has to count the dots,” McCabe said.

Computer genetic metrics in the fly brain reveal gender differences

Schematic pipeline of molecular genetic, microscopy and computational technologies used to count cells throughout the Drosophila larval brain. Credit: B. McCabe (EPFL)

Using this method, the team found that female larval brains have about 10,300 neurons, between 15 to 30% smaller than previously estimated, and about 3,800 glial cells, three times that more than previously predicted.

The brain of male larvae has about 9,400 neurons, almost 10% fewer neurons than females. But they had about 4% more glial cells than their female counterpart, the researchers found. “In the larval stage, Drosophila does not have any external sex organs, so finding such a large difference is surprising,” McCabe said.

Further analysis conducted by mathematicians led by Kathryn Hess, director of the Laboratory for Topology and Neuroscience and a Professor at the EPFL School of Life Sciences, confirmed the gender differences in the brain. If researchers analyzed data using methods from an area of ​​mathematics called topology, which studies the shape of the data, they could predict that the animal’s sex would have 99% accuracy just from the topology of its brain. “The emerging global structure of the male brain seems to be different from the female brain,” Hess said. The findings are published in eLife.

Although there is currently no explanation for these sex differences, McCabe hypothesizes that behavioral differences may contribute to different numbers of neurons and glial cells between male and female brains. However, he added, the findings suggest that when studying behaviors or brain cables, researchers should look at the same sex.

Now that researchers have determined the exact number of brain cells in Drosophila larvae, they want to investigate how neurons are connected to each other and how they function in the brain. To do this, McCabe plans to use a similar set of technologies linking genetic imaging tools to computer-assisted data analysis — a technique the researchers call “robogenetics,” or genetics for computers. Robogenetics could turbocharge computer-based data analysis and enable the investigation of biological data by theoreticians, McCabe said. Such an interdisciplinary approach, he added, is one of the purposes of the newly opened EPFL Center for Imaging, a hub for advanced imaging and analysis.

The researchers noticed a barrier to proliferation inside the fly’s brain

More information:
Wei Jiao et al, Intact Drosophila central nervous system cellular quantitation reveals sexual dimorphism, eLife (2022). DOI: 10.7554 / eLife.74968

Journal information:

Provided by the Ecole Polytechnique Federale de Lausanne

Citation: Computer genetic metrics in fly brain reveal sex differences (2022, July 19) retrieved July 19, 2022 from -sex.html

This document is under copyright. Except by any fair dealing for the purpose of private study or research, no part may be reproduced without written permission. Content is provided for informational purposes only.

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