Connecting the Dots: Mapping the Fruit Fly Brain

How the work of US labs is revolutionising our understanding of the brain…

Written by: Chi Yu Lee

Art by: Lisa Farya Burna-Asefi


The fruit fly Drosophila melanogaster has long been used as a model organism to understand the principles of inheritance, the mechanism of development and the molecular basis of behaviours. Several Nobel prizes have been awarded for medical research on circadian rhythm, early embryonic development, and innate immunity, undertaken primarily on these insects. In neuroscience, researchers have developed various techniques to track neurons in flies’ nervous systems and monitor their behaviours. Fruit flies demonstrate a variety of behaviours with only 250,000 neurons, a number far smaller than in both the rodent brain (75 million neurons) and the human brain (more than 80 billion neurons), which makes improving our understanding of the basic principles of neurons involved in specific behaviours far easier.

At Janelia Research Campus in the US, researchers have been working to understand the neural basis of behaviour by mapping the fruit fly brain in detail. They took several approaches, including using electron microscopy (EM) to image sections of fruit fly brains at high resolution and reconstruct them into a ‘brain atlas’. The resolution, of up to nanometers, can reveal details that conventional light microscopy could not, allowing the visualisation of synapses and the quantification of connection between neurons.  Nevertheless, each electron microscope section is minuscule, making the process laborious: a set of 160 neurons in the fly olfactory (smell) system took the research team more than 1100 hours to reconstruct. Therefore, they also developed techniques and algorithms to speed up the process of data acquisition. Before this work, comprehensive brain atlases, or so-called connectomes, were only completed in C. elegans and ascidian, organisms with only hundreds of neurons. The connectome projects at Janelia, which aim to construct the whole fly brain, therefore may add an important new dimension to our understanding of neuroscience.

Over the past few years Janelian researchers, in collaboration with fly experts around the world, have published several connectome papers on Drosophila larvae. Together, they discovered previously unknown neural circuits and created models to predict how neural circuits receive different sensory inputs – such as air-puff stimuli – and generate corresponding motor outputs like strolling or rolling. Their recent publication identified novel canonical circuits in each subregion of ‘mushroom bodies’, high-order brain regions important for learning and memory. These models can serve as references for similar neural populations in adult fly brains.

Now researchers around the world are able to analyse the connections of neurons of interest, further investigating their functions. The publicly available connectome information is just a starting point to uncovering the neural mechanism underlying behaviors. With improvements in imaging speed and automated annotation, the timeline of constructing electron microscopy-based atlases of an animal brain can be shortened significantly. Hopefully in the future, we will be able to apply this to larger animals like mammals, adding to our limited knowledge of the most complex organ: the human brain.

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