HUGE STEPS ON A TINY BRAIN: Unraveling the Fruit Fly Connectome and Approaches for Comparative Connectomics

Abstract

A map of the brain’s circuits, known as the connectome, is essential for understanding behaviour. Obtaining a high-resolution connectome, where individual neurons and synapses are annotated, has long been a challenge, with most complete connectomes containing just a few hundred neurons and synapses. However, a groundbreaking achievement has been the recent elucidation of the connectome of the fruit fly, Drosophila melanogaster, which includes thousands of neurons and millions of annotated synapses. These comprehensive connectomes are invaluable as they enable the comparison of neural connections between different brains, even across species, shedding light on how changes in brain connectivity can impact brain function and behaviour. This review explores the path that led to the creation of the most extensive and detailed connectome to date. It also provides an overview of the strategies for approaching comparative connectomics. The development of these extensive connectomes has been driven by advances in electron microscopy systems and computational tools, which have streamlined the automatic annotation of neurons and synapses. While traditional methods for comparing connectomes have primarily relied on morphological neuron comparisons, there is a growing demand for approaches rooted in the connectivity of neurons. Graph matching emerges as a pivotal technique to determine neuron correspondences across different brains, yet challenges persist in finding an accurate and scalable solution, particularly for large brains.