Towards mapping spatial transcriptome of an entire vertebrate brain

Abstract

Both the brain’s substantial complexity and technical challenges in monitoring and manipulating brains present challenges for understanding this essential organ. Zebrafish, for their modest brain size and transparency in the larval stage, serve as a model organism for whole-brain in vivo imaging and modeling. While calcium imaging generates substantial amounts of neural activity data, the lack of molecular information for individual neurons in a purely activity readout approach limits further biological interpretation. Recent advancements in in situ sequencing allow RNA profiling in its spatial context, which provides rich information on cell types and cell states. In this thesis, we adapted the expansion in situ sequencing(ExSeq) protocol for larval zebrafish brain slices. In brief, performing two rounds of expansion on zebrafish brain slices enabled us to obtain spatially localized sequencing readouts. This lays the foundation for mapping the spatial transcriptome of an entire vertebrate brain.