Unraveling behavioral individuality in Drosophila melanogaster: An automated high-throughput screening approach

Despite being genetically identical and reared under identical conditions, individual animals exhibit behavioural differences, which we call individuality. It remains unclear where these differences emerge in the causal cascade from transcription to gene products, cellular physiology, and neural circuit information processing. Measuring individuality requires a large number of measurements, either by repeating measurements from the same individual or gathering multiple measurements from multiple individuals with identical genetic and developmental backgrounds. Since cognitive behaviours are influenced by experience, the first strategy is ineffective to study individuality in cognition. We developed a high-throughput behavioural screening platform to measure cognition in the fruit fly, Drosophila melanogaster. Drosophila with its sophisticated molecular and neuronal tools, express a myriad of behavioural phenotypes making it an excellent model for investigating behaviour and cognition. Using our platform, we measured learning in flies in parallel batches of 64 across 6,000 flies from 90 isogenic lines. Our results show that genetics plays an essential role in shaping the distributions of individual behaviours. Additionally, genotype-specific biases influence individual experiences, which, along with learning, lead to the dynamic evolution and diversification of individual behaviour, even in a uniform environment. We experimentally determined that life experience, genetics, and learningâ each in that orderâ shape the momentary expression of individual behaviour. Finally, while genetic association studies often suggest the opposite, we demonstrate that life experience significantly reduces the predictive power of genetics for learning-dependent behaviour. To further standardize fly handling and short-term experiences, we developed a robotic platform that autonomously conducts behavioural experiments, increasing throughput to screening more than a thousand flies in a day, for fast and efficient screening.