Towards “Solving” a Vertebrate’s Brain: Mapping Neural Circuit Structure and Function in Larval Zebrafish

Recent developments in imaging technology are extending our ability to map brain structure and function with increasing spatial and temporal resolution. Nevertheless, the great mysteries of the brain have yet to be solved. Particularly, it is still unknown how intact neural circuit structure gives rise to function in healthy brains and how altered structure gives rise to dysfunction in diseased ones. In this talk, I will describe ongoing efforts for addressing these questions, taking advantage of the utility of the larval zebrafish as a model for both technology development as well as its application in neuroscience. First, I will focus on epilepsy and show how neural activity imaging in larval zebrafish chemical and genetic seizure models revealed distinct dynamics associated with different seizure types. Identifying and quantifying such phenotypes provides a foundation for the development of novel treatments for the broad spectrum of epilepsies and seizures affecting humans. Next, I will describe how I am applying Expansion Microscopy, a recent super-resolution microscopy method, to reveal the structural underpinnings of neural activity dynamics. This includes, for example, characterizing synaptic structure, tracing neural projections and mapping connectivity throughout the brain. Finally, I will lay out several future directions of technology advancement for combining neural activity dynamics information with cellular identity and connectivity, towards solving the great mystery of how the brain’s structure gives rise to its function.

This research was conducted in the Yanik and Boyden labs at MIT.