A fundamental question in neuroscience is how these vast, complex circuits are assembled during development. A recent study by a group of researchers including Erdem Varol, Assistant Professor of Computer Science and Engineering and a member of the Visualization, Imaging and Data Analysis Center, has provided new insights into this problem by studying how the neurons responsible for leg movement in fruit flies (Drosophila melanogaster) establish their connections.

The researchers developed ConnectionMiner, a novel computational tool that integrates gene expression data with electron microscopy-derived connectomes. This tool enabled them to infer neuronal identities and predict synaptic connectivity with remarkable accuracy. Their findings, published on bioRxiv, offer a blueprint for understanding how neurons wire themselves into functional circuits.

Neurons form connections based on genetic and molecular cues, but identifying the precise mechanisms behind this process has been difficult. In the fruit fly, roughly 69 motor neurons (MNs) in each leg are responsible for controlling movement. These neurons receive input from more than 1,500 premotor neurons (preMNs) through over 200,000 synapses. The challenge lies in understanding how each MN finds the right preMN partners and how these connections are established at the molecular level.

By applying single-cell RNA sequencing (scRNAseq) at multiple developmental stages, the researchers tracked how different gene families, particularly transcription factors (TFs) and cell adhesion molecules (CAMs), shape the unique identities of MNs. They discovered that these molecular signals not only define neuronal types but also correlate with the strength of their synaptic connections.

This research has far-reaching implications. Understanding the molecular rules that govern neural connectivity in fruit flies could inform studies of more complex nervous systems, including our own. The principles uncovered here might help explain how neural circuits form during development, how they recover from injury, and even how neurodevelopmental disorders arise when connectivity goes awry.

Source: https://engineering.nyu.edu/news/new-research-uses-ai-unravel-complex-wiring-motor-system