There is really ResNet in the brain! The world's first 'Drosophila Brain Connectome' is released: it took more than ten years to reconstruct 3,000 neurons and more than 500,000 synapses!

Although modern deep learning has long since broken away from imitating "biological neural networks", understanding the operating mechanism of the biological brain is still very helpful for the future development of neural network models.

The way brain circuits are structured affects the brain's computational capabilities, but so far, no specific structure of the brain has been seen except in some very simple organisms.

In November last year, researchers from many top institutions such as the University of Cambridge, Johns Hopkins University, and Janelia Research Park uploaded a paper on Biorxiv. AfterMore than ten years of arduous research, for the first timecompletelyreconstructed the brain connectome of the "Drosophila larvae".

Paper link: https://www.science.org/doi/10.1126/science. add9330​

On March 10, the relevant results were published in the magazine "Science".

Joshua Vogelstein, an associate professor at Johns Hopkins University and one of the authors of the paper, said that fruit flies are closer to the human brain in many ways than other organisms, and some areas correspond to decision-making. Some areas correspond to learning and some to navigation; and the brains of Drosophila larvae and humans are also divided into left and right sides.

In the analysis of the fruit fly brain, we can also find some results in modern neural networks, such as recurrent neural networks and shortcut paths between multi-layer networks (residual network ResNet) etc., may inspire improvements to machine learning models.

Good news: The reconstructed Drosophila larval brain connectome includes 3016 neurons

Bad news: People have 86 billion neurons.

Complete reconstruction of the Drosophila larval brain

The brain is mainly composed of "neuron cells". Adjacent neurons can interact with each other at the connections between synaptic cells. To send out a signal, one neuron releases a "neurotransmitter" and another neuron receives the chemical. The complete map of neurons and synapses in the brain is called the connectome. Studying the connectome is crucial to understanding how the brain generates behavior.

The main process for reconstructing the connectome is to cut the brain into ultra-thin (20 micron) slices, and then use the electron flow of an electron microscope to image the slices, such as

The brain of a fruit fly larvae the size of a grain of salt is cut into thousands of pieces. If anything goes wrong, you have to start all over again.

For some simple organisms, it is relatively easy to construct a complete connectome. The first fully drawn It is Caenorhabditis elegans, which has only 302 neurons in its entire body. It was mapped in the 1980s.

But so far, researchers have mapped complete synaptic connectomes for only three organisms, each with just a few hundred brain neurons.

In 2020, researchers from Google and Janelia Research Park released a 3D model of the Drosophila brain connectome, containing 25,000 Drosophila neurons. Spanning different cell types and multiple brain regions, the model is not a complete brain, and even then it contains only a quarter of the 100,000 neurons in an adult fruit fly.

There are also some research groups that are studying the connectome of animals with larger brains, such as insects, fish, mammals, etc. However, due to the large number of neurons, the main research method is to partition the brain. Studying them in isolation results in the inability to reconstruct brain regions that are interconnected across space.

The complete connectome reconstructed this time belongs to the larvae of Drosophila melanogaster. Drosophila melanogaster can show a very rich behavior, including learning, value calculation and behavioral selection, and is closely related to adult fruit flies. Flies and larger insects have homologous brain structures.

Powerful genetic tools can be used to selectively manipulate or record individual neuron types in tractable In model systems, hypotheses about the functional roles of specific neuronal and circuit motifs revealed by the connectome can be readily tested.

The research team cut the brain of a "6-hour-old" Drosophila melanogaster larvae into 4841 pieces, scanned them with a high-resolution electron microscope, digitized the images and then reassembled them into a three-dimensional image; with the assistance of computer analysis, the final map generated contains 3,016 neurons and 548,000 synapses.

The residual network is hidden inside

The researchers conducted a detailed analysis of the brain circuit structure, including connections and neuron types, network hubs ) and neural circuit diagrams.

The majority (73%) of the brain's input and output hubs (in-out hubs) are "post-synaptic centers for learning centers" or "dopaminergic neurons that drive learning" "presynaptic center"; using graph spectral embedding technology, hierarchically clustered neurons based on synaptic connectivity were divided into 93 types that are internally consistent based on other characteristics such as morphology and function. sex.

The researchers also developed an algorithm to track signal propagation in the brain's multisynaptic pathways and analyzed feedforward (from sensory to output) and feedback pathways. , multisensory integration and cross-hemisphere interactions.

Extensive multisensory integration is found in the brain, and at varying depths from sensory neurons to output neurons Multiple interconnected pathways form a distributed processing network.

The brain has a highly recurrent structure, and 41% of neurons receive long-range cyclic input. However, the distribution of loops is not uniform, and the loop rate is particularly high in areas involving learning and action selection. high.

Dopaminergic neurons, which drive learning, are among the most common neurons in the brain.

There are many contralateral neurons that project to both hemispheres of the brain. They are in-and-out centers. out hubs), synapse with each other, promoting extensive communication between the two hemispheres of the brain; the article also analyzes the interaction between the brain and nerves.

Researchers found that descending neurons target a small group of premotor elements that play an important role in switching locomotor states. role.

Conclusion

The complete brain connectome of Drosophila larvae will provide the basis for other theoretical and experimental studies of brain function for a long time to come, generated in this study The methods and computational tools will facilitate future analysis of connectomes.

Although the details of brain organization vary across the animal kingdom, many neural circuit structures are conserved.

As the brain connectomes of more other organisms are mapped in the future, comparisons between different connectomes will reveal common and potentially optimal circuit structures, as well as between organisms. Behavioral differences in traits.

Some structural features observed in the Drosophila larval brain, including multi-layered shortcuts and prominent nested loops, can be The discovery of in advanced artificial neural networks may be able to make up for the current network's problems in depth and generalization of processing tasks. These features can also increase the brain's computing power and overcome the physiological limitations of the number of neurons.

Future analysis of the similarities and differences between the brain and artificial neural networks may help understand the brain's computational principles and may inspire new machine learning architectures.

Related comments

Gashpal Yekayi, professor of neuroscience at the University of Exeter, UK, said , all neurons of the brain are reconstructed and all neural connections analyzed. He called the work "very important."

Katherine Dulac of Harvard University in the United States believes that these data reveal the "deep logic" of these neuronal connections.

However, Scott Emmons of the Albert Einstein College of Medicine in New York believes that simply mapping synapses does not provide the full picture.

Emmons mapped the connectome of the male and female Caenorhabditis elegans in 2019. Neurons also communicate through slowly released chemicals such as hormones and other connections between cells. Connections (i.e. gap junctions) communicate with each other.

All this must be taken into account, but only synapses are included in the newly drawn connectome.

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