DSSS - Predicting individual behaviour: from genes to the physical structure of the entire brain

Understanding how evolution shapes the brain and how individual behaviour emerges from its physical architecture is a central challenge in neuroscience and evolutionary neurobiology. Despite major advances in mapping genotype to phenotype and brain structure to function, predicting natural, individual behaviour from genes or brain anatomy remains elusive. This limitation stems from the deep entanglement of genotype and environment. Genotype-by-environment interactions are uniquely intertwined within individuals: each individual, by definition, experiences distinct environments that, through learning and adaptation, give rise to unique phenotypic trajectories.How, then, can we study and access the genetic or mechanistic basis of individuality such that we might one day predict individual behaviour? In this talk, I will present an integrative approach my lab has developed to understand individuality and its genetic and structural foundations. Our framework combines whole-brain micro-computed tomography, topological data analysis, multivariate modelling, and robotic automation of behavioural screening to quantify the structural complexity of intact brains and relate it to individual behaviour.Using thousands of genetically diverse Drosophila melanogaster individuals, we uncovered striking natural variation in both individual behaviour and individual brain architecture. By harnessing this natural genetic and individual diversity, we identified multiscale architectural “blueprints” of the brain capable of predicting a broad spectrum of behaviours, from locomotion to learning. We find that when brain structural complexity is modelled across scales, from local microstructure to global anatomy, it reveals predictive, mechanistic insights into the structure-function relationship of the brain. Together, these findings demonstrate that behavioural diversity arises from the brain’s multiscale organization, underscoring the need to consider whole-brain structure to uncover the physical principles underlying behavioural individuality.