summary: Researchers have published the most comprehensive connectome of the adult Drosophila nerve cord, which resembles the human spinal cord, providing an excellent resource for the scientific community.
Constructed from approximately 23,000 neurons, the connectome reveals a complex network that controls motor functions in flies. The data are already yielding new insights and challenging previous theories about fly movement.
This achievement not only advances our understanding of Drosophila neurology, but also serves as a model for future similar projects.
- The Drosophila nerve cord connectome contains approximately 23,000 neurons, 10 million presynaptic sites and a density of 74 million postsynaptic sites.
- This is the most detailed and complete connectome of the adult Drosophila nerve cord to date.
- The connectome has already revealed that some behaviors involving the same muscles use different premotor microcircuitry, contradicting existing theories.
sauce: Janelia Research Campus
Already this year, researchers published a wiring diagram of the brain of a fruit fly larva. The complete adult female fly brain and optic lobe connectome is expected to be completed in 2023, and the complete male fly nervous system connectome will follow soon.
On June 6, US and UK scientists Janelia and her collaborators released a wiring diagram of an adult male’s nerve cord, called the MANC, adding another piece to the connectome puzzle.
With a density of approximately 23,000 neurons, 10 million presynaptic sites, and 74 million postsynaptic sites, the MANC is the most detailed and complete connectome of the adult Drosophila nerve cord and the most regulating human construct. It is a structure similar to the spinal cord. Part of a fly’s motility.
The unprecedented detail in this map of neurons and their connections helps scientists understand how flies move their legs and flap their wings.
Lined end-to-end, the 23,000 neurons that make up the MANC connectome are about 44 meters long.
Preprints released with the connectome data describe different cell types, their origins and connections, and the biological insights that are beginning to emerge from the data. Drosophila is an important organism that neuroscientists use to investigate how the nervous system works, so the presence of the connectome is important to reveal how cells work together to enable behavior. It is important.
“Once you see the whole network, you can ask the big questions about the organization,” says Gwyneth Card, an HHMI research fellow at Columbia University’s Zuckerman Institute and former Janelia group leader who helped lead the project.
The released MANC and other connectomes follow in the footsteps of the half-brain connectome published by Janelia scientists in 2020. At the time, the hemibrain, part of the adult fly brain, was the largest and most comprehensive wiring diagram ever completed. A feat that many thought was impossible is possible.
The liberation of the hemibrain has generated further support and interest in the connectome effort. Researchers are now filling in the missing hemibrains and are close to achieving their goal of mapping the entire central nervous system of both adult male and female fruit flies.
“This train keeps running,” says Card. “You are still only seeing the beginning.”
Construction of MANC
The MANC connectome was constructed using methods similar to those used for mapping the hemibrain. The Janelia team prepared nerve cord samples and layer after layer of nanometer-thick slices imaged on a focused ion beam scanning electron microscope. Google’s algorithms and computers stitched together the images and performed a first pass to identify neurons.
Janelian and her team of collaborators then set out to calibrate the data. This is the manual work of ensuring that the neuron shapes and connections are correct, and one of the most time-consuming parts of the process. Due to the COVID-19 pandemic, the team developed software that works on their home computers. This, along with additional funding from the Wellcome Trust, meant that international collaborators could more easily support this effort.
“It’s perfectly calibrated, and you can find the same neurons on both sides of the fly, so you can tell your colleagues, ‘This is reliable,'” said neuroscientist Greg Jefferis of the MRC Molecular Biology Laboratory. To tell. He’s from the University of Cambridge and another member of the FlyEM project team steering committee, he’s the project leader.
The University of Cambridge researchers also identified different cell types, where they are located in the fly’s body and from which stem cells they originated, helping to elucidate some of the organizational principles.
“The ventral nerve cord has been basically viewed as a black box,” says Lisa Marin, a researcher at the University of Cambridge who led the cell-typing effort.
“The majority of neurons have not yet been identified. So a large part of our process has been to divide these into smaller populations and drill down for connectivity.”
Examination of connectome data is already beginning to reveal some surprising things. Card and her team found that some actions involving the same muscles used different pre-premotor circuits rather than the same circuits as previously thought.
Jeffries and his team describe the complex, repetitive circuits that control the legs and surprisingly find that the interconnections that coordinate the legs are different from existing models.
More insights will come from MANC as other researchers start exploring the data. Data can be accessed through Janelia-developed online tools neuPrint and Clio.
“It’s clear that these connectomes are very abundant and really just a starting point for trying to understand how this system works,” Card said. “Investigating this network requires the community as a whole to delve into a wide variety of different behaviors that people study in different situations. That’s how we uncover higher principles.” .”
In addition to providing scientific insights, this project will also serve as a model for other groups working on the connectome.
“This kind of collaboration is absolutely necessary when people start moving into things like the mouse connectome,” said Lou Scheffer, principal scientist at Janelia and member of the FlyEM team.
“I can’t think of any way that a single organization could do that. So this is a prototype for that kind of cooperation.”
About this neuroscience research news
Original research: closed access.
“Male ventral nerve cord connectome of Drosophila]Written by Shinya Takemura and others. Bio RXiv
“Systematic annotation of the complete adult male Drosophila nerve cord connectome reveals principles of functional organizationby Elizabeth C. Marin et al. Bio RXiv
Connectome of the male ventral nerve cord in Drosophila
Animal behavior is expressed primarily by neural control of muscles. Therefore, understanding how the brain controls behavior requires mapping neural circuits down to motor neurons.
We have previously collected large-volume electron microscopy datasets of neural tissue and established techniques to fully reconstruct neuronal morphology and their chemical synaptic connections throughout the volume. These tools were used to generate most of the high-density wiring diagrams, or connectomes. Drosophila central brain.
However, in most animals, including flies, the majority of motor neurons are located in the near-corporal nerve centers outside the brain: the spinal cord in mammals or the ventral nerve cord (VNC) in insects.
In this paper, we extend our efforts to map the complete neural circuit for behavior by generating a connectome for the VNC of male flies.
Systematic annotation of the complete adult male Drosophila nerve cord connectome reveals principles of functional organization
Our sister paper (Takemura et al., 2023) presents the first fully calibrated connectome of nerve cords in walking and flying animals. The basic connectome consists of the morphology of neurons and the connections between them.
However, to efficiently navigate and understand this connectome, an annotation system that systematically classifies and names neurons and links them to existing literature is critical.
In this paper, we first define systematic cell types of intrinsic interneurons and sensory neurons in the VNC, first by a system of hierarchical coarse annotations, then by grouping left-right and serially homologous neurons. describes a comprehensive annotation of the VNC connectome. Descending neurons and motor neurons enter (Cheong et al., 2023).
We assign sensory modalities to over 5,000 sensory neurons, cluster them by connectivity, and identify lamellar tissues that appear to correspond sequentially to homologous cell types and peripheral topography. We identified the developmental neuroblasts from which most VNC neurons originated and confirmed that (in most cases) all secondary neurons of each hemilineage expressed a single neurotransmitter. bottom.
Neuroblast hemi-lineages repeat continuously along nerve cord segments and generally exhibit consistent inter-semi-lineage connectivity throughout the neuromere, leading to the notion that hemi-lineages are a major organizational feature of VNC. I back it up.
We also found that more than one-third of individual neurons belonged to consecutively homologous cell types. This was important for distinguishing between motor and sensory neurons throughout the leg neuropil. Classifying interneurons by their neuropil innervation pattern provides an additional organizational axis.
More than half of the VNC’s intrinsic neurons appear to be leg-specific, and are mostly confined to single-leg neuropils. In contrast, inhibitory interneurons connecting different leg neuropiles, especially those that cross the midline, appear to be rarer than the canonical model of motor circuitry would predict.
Our annotations have been released as part of the neuprint.janelia.org web application and also serve as the basis for programmatic analysis of the connectome via dedicated tools described in this paper.