Spontaneous Brain Activity Emerges from Pairwise Interactions in the Larval Zebrafish Brain.

Brain activity is characterized by brainwide spatiotemporal patterns that emerge from synapse-mediated interactions between individual neurons. Calcium imaging provides access to recordings of whole-brain activity at single-neuron resolution and, therefore, allows the study of how large-scale brain dynamics emerge from local activity. In this study, we use a statistical mechanics approach-the pairwise maximum entropy model-to infer microscopic network features from collective patterns of activity in the larval zebrafish brain and relate these features to the emergence of observed whole-brain dynamics. Our findings indicate that the pairwise interactions between neural populations and their intrinsic activity states are sufficient to explain observed whole-brain dynamics. In fact, the pairwise relationships between neuronal populations estimated with the maximum entropy model strongly correspond to observed structural connectivity patterns. Model simulations also demonstrated how tuning pairwise neuronal interactions drives transitions between observed physiological regimes and pathologically hyperexcitable whole-brain regimes. Finally, we use virtual resection to identify the brain structures that are important for maintaining the brain in a physiological dynamic regime. Together, our results indicate that whole-brain activity emerges from a complex dynamical system that transitions between basins of attraction whose strength and topology depend on the connectivity between brain areas.