Researchers have completed a detailed map of every neuron and neural connection in the brain of a male fruit fly, creating the second complete connectome of the species. The work gives scientists a new tool to study how brains process information at the level of individual neurons and their connections.
The project was a collaboration between biologists at the Howard Hughes Medical Institute’s Janelia Research Campus and computer scientists at Google. The male fly connectome follows the completion of a female Drosophila connectome earlier this year, allowing researchers to compare the complete neural wiring of males and females of the same species.
A connectome maps the location of neurons and the synapses connecting them. Although the fruit fly’s nervous system contains about 150,000 neurons, researchers identified more than 300 million individual synaptic connections in the brain, highlighting the complexity of even a relatively small nervous system.
Building the map took about four years. Researchers dissected a fruit fly brain and part of its ventral nerve cord, sliced the tissue into hundreds of sections and used electron microscopy to image them at high resolution. Artificial intelligence was then used to reconstruct the brain’s three-dimensional architecture, trace individual neurons and identify synapses.
The AI systems were refined through repeated checks by human proofreaders, creating an iterative process in which researchers’ feedback was used to improve the algorithms. The techniques and software developed during the project are intended to eventually be applied to more complex nervous systems, including those of vertebrates such as mice.
Comparing the male and female connectomes has already revealed differences in their neural wiring. Researchers identified 289 neurons unique to males, 71 unique to females and 138 found in both sexes but differing in shape and connectivity. About 90% of the male-specific neurons expressed the genes doublesex or fruitless, while the remaining 10% did not, suggesting that some sex-specific neural characteristics may develop indirectly through interactions between neighbouring cells.
The sex-specific neurons tended to be concentrated in higher-level processing areas involved in neural integration and decision-making rather than basic sensory or motor circuits, although there were exceptions, including neurons involved in detecting sex-specific pheromones.
The completed connectome also provides neuroscientists with a detailed wiring diagram against which theories of brain function can be tested. Researchers say the availability of such a map represents a major shift from theorising about how brains might work to testing how specific neural circuits could produce particular functions.
Researchers now hope that advances in technology will reduce the time and cost of producing connectomes, much as genome sequencing became faster and cheaper. With only two complete fruit fly connectomes currently available, they say many more will be needed to understand how much natural variation exists between individual brains of the same species.
