The first map of the brain of insect larvae is a landmark achievement led by Cambridge scientists

The first map showing each neuron in the brain of a fruit fly larva and how they are connected together has been created by Cambridge scientists.

The extraordinary achievement represents a major advance, as the brains of very simple organisms have so far been mapped.

Morphology of all brain neurons in a Drosophila larva, reconstructed from size clamp resolution EM.  Image: MRC Laboratory of Molecular Biology
Morphology of all brain neurons in a Drosophila larva, reconstructed from size clamp resolution EM. Image: MRC Laboratory of Molecular Biology

It will aid in our understanding of how the brain works and how signals are transmitted through it at the neural level, leading to behavior and learning.

The research, which could also lead to future treatments, was led by the groups of Professor Marta Zlatek and Professor Albert Cardona in the Department of Neurobiology at the MRC Laboratory of Molecular Biology in Cambridge, along with members of their groups at the University of Cambridge department. Zoology and the Departments of Physiology, Development, and Neuroscience respectively, in collaboration with Joshua T Vogelstein at Johns Hopkins University.

Their map – or “neural network” – contains the 3,016 neurons present in the brain of a caterpillar Drosophila melanogaster, along with the detailed circuits of the neural pathways within it. They meticulously mapped the brain and its 548,000 synapses — the connection points that connect neurons — using computer-aided reconstructions from electron micrographs.

It is the largest complete brain neural network ever mapped.

Professor Zlatek said: “The way the brain circuitry is organized affects the computations that the brain can perform. But up until this point, we had not seen the structure of any brain except the roundworm.” C. elegans, tadpole of a lower chordate and a marine annelid larva, all containing several hundred neurons. This means that neuroscience has been working mostly without circuit maps.

Professor Marta Zlatek.  Image: MRC Laboratory of Molecular Biology
Professor Marta Zlatek. Image: MRC Laboratory of Molecular Biology

“Without knowing the structure of the brain, we guess at the way computations are carried out. But now, we can begin to gain a mechanistic understanding of how the brain works.”

Advances in electron microscopy made it possible to image the entire brain relatively quickly, before brain circuits were reconstructed from the data.

The technology is not yet capable of addressing larger brains, such as those of mammals, but the researchers say the work will nonetheless be a permanent reference for future studies of brain function in other animals.

“All brains are the same — they are all networks of interconnected neurons — and all brains of all kinds must perform many complex behaviours: they all need to process sensory information, learn, choose actions, navigate their environments, choose food, learn about their idiosyncrasies, escape.” from predators, etc.

“In the same way that genes are preserved throughout the animal kingdom, I believe the forms of the basic circuits that carry out these basic behaviors will also be preserved,” said Professor Zlatek, whose colleague Dr. Michael Winding in the Department of Zoology was among the participants. .

The brain structures of Drosophila larvae are similar to those of adult Drosophila and larger insects. It has a rich behavioral repertoire, including learning, calculating values, and choosing action.

Until now, scientists have only been able to build a picture of the circuitry of synaptic resolution for larger brains by mapping selected regions in isolation.

The team constructed their picture of the fruit fly larva’s network using thousands of slices of the larva’s brain imaged with a high-resolution electron microscope and annotated the connections between neurons.

They developed computational tools to identify potential pathways for information flow and different types of circuit patterns in the insect brain, and discovered that some structural features are similar to modern deep learning architecture.

“The most challenging aspect of this work was understanding and interpreting what we saw. We encountered a complex neural circuit with a lot of structures.

In collaboration with the groups of Professor Priebe and Professor Vogestein at Johns Hopkins University, we have developed computational tools to predict relevant behaviors from structures. By comparing this biological system, we can also inspire better artificial networks,” said Professor Zlatek.

LMB described the work as a “landmark achievement” that opens the door to future studies of neural circuits and brain function.

Professor Albert Cardona.  Image: MRC Laboratory of Molecular Biology
Professor Albert Cardona. Image: MRC Laboratory of Molecular Biology

Joe Latimer, chair of neurosciences and mental health at the Medical Research Council, said: “This is exciting and important work by colleagues in the MRC Molecular Biology Laboratory and others.

“Not only have they mapped every single neuron in the insect’s brain, but they’ve also worked out how each neuron is connected. This is a huge step forward in addressing key questions about how the brain works, particularly how signals move through neurons and synapses leading to behavior,” This detailed understanding may lead to therapeutic interventions in the future.”

The researchers will now dive deeper into the findings to discover, for example, the brain circuits required for specific behavioral functions, such as learning and decision-making. They also want to probe activity in the entire neural network while the insect is active.

The study was published last Friday (March 10) in the Sciences.

Deep dive into the brain Drosophila Larva

After brain mapping Drosophila In a caterpillar with meshing resolution, the researchers performed detailed analyzes of circuit architecture, including connection types, neurons, network axes, and circuit decorations.

They found out which neurons sent a signal (presynaptic) and which received messages (postsynaptic).

They found that 73 percent of the internal and external communication axons in the brain were postsynaptic to the learning center or presynaptic to dopaminergic neurons, which drive learning.

They used spectral modulation of the graph to group neurons hierarchically by synaptic connectivity into 93 types of neurons that were internally compatible with features such as morphology and function.

They have developed a new algorithm to track the propagation of a brain signal across multiple synaptic pathways – including multiple synapses. Pathways of ‘feed-forward’ (sensory-to-output), ‘feedback’, multisensory integration and interactions were analyzed across the hemisphere.

Fruit fly larva.  Image: MRC Laboratory of Molecular Biology
Fruit fly larva. Image: MRC Laboratory of Molecular Biology

They identified a broad multisensory integration throughout the brain, with many interconnected pathways from sensory neurons to efferent neurons forming a distributed processing network.

They found that the structure of the Drosophila brain was highly repetitive, with 41 percent of neurons receiving long-range repetitive inputs.

Redundancy is particularly noted in areas involved in learning and action selection. Dopaminergic neurons that drive learning have been found to be among the most frequent neurons in the brain.

Extensive communication across the two hemispheres has been achieved through interneurons of axons that house synaptic neurons synapsing with each other.

The researchers also analyzed the interactions between the brain and nerve cord, and found that descending neurons targeted a minority of premotor elements, which can be important in switching between motor states.

A subset of descending neurons targeted lower-order postsensory interneurons, which they believe modulate sensory processing.

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