Development of a framework to link functional activity and circuit wiring diagrams in the zebrafish larva brain

In recent years, there has been a significant increase in the developing of techniques to study the brain, both in terms of the function and of the connectivity organization. Whole brain dense anatomical reconstruction at synaptic resolution have provided insight into the brain architecture and how the information is transmitted. However, these reconstructions, even when the synaptic input/output relationship are known, are still far from revealing the general connectivity patterns of the neuronal circuits across the brain and their functional organization in networks. On the other hand, light based techniques allow the functional characterization of the neuronal activity associated with resting state activity or sensory-driven dynamics. Here, we present two methods to analyze the circuit mechanisms on the zebrafish larvae, a small vertebrate with a completely optical accessible brain. First, a tool for identifying functionally relevant networks based on their structural connectivity patterns which is adaptable to different anatomical datasets with or without identified synapses. Second, an alternative optical layout for high resolution whole-brain imaging which can be used to reconstruct the brain dynamics during sensory stimulation. The combination of these two tools can provide a deeper understanding on how the structure of the nervous system supports the flow of information and offer a more accurate basis for the formulation of models of the circuit working principles.