TY - JOUR T1 - Whole-brain serial-section electron microscopy in larval zebrafish JF - bioRxiv DO - 10.1101/134882 SP - 134882 AU - David Grant Colburn Hildebrand AU - Marcelo Cicconet AU - Russel Miguel Torres AU - Woohyuk Choi AU - Tran Minh Quan AU - Jungmin Moon AU - Arthur Willis Wetzel AU - Andrew Scott Champion AU - Brett Jesse Graham AU - Owen Randlett AU - George Scott Plummer AU - Ruben Portugues AU - Isaac Henry Bianco AU - Stephan Saalfeld AU - Alex Baden AU - Kunal Lillaney AU - Randal Burns AU - Joshua Tzvi Vogelstein AU - Alexander Franz Schier AU - Wei-Chung Allen Lee AU - Won-Ki Jeong AU - Jeff William Lichtman AU - Florian Engert Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/05/07/134882.abstract N2 - Investigating the dense meshwork of wires and synapses that form neuronal circuits is possible with the high resolution of serial-section electron microscopy (ssEM)1. However, the imaging scale required to comprehensively reconstruct axons and dendrites is more than 10 orders of magnitude smaller than the spatial extents occupied by networks of interconnected neurons2—some of which span nearly the entire brain. The difficulties in generating and handling data for relatively large volumes at nanoscale resolution has thus restricted all studies in vertebrates to neuron fragments, thereby hindering investigations of complete circuits. These efforts were transformed by recent advances in computing, sample handling, and imaging techniques1, but examining entire brains at high resolution remains a challenge. Here we present ssEM data for a complete 5.5 days post-fertilisation larval zebrafish brain. Our approach utilizes multiple rounds of targeted imaging at different scales to reduce acquisition time and data management. The resulting dataset can be analysed to reconstruct neuronal processes, allowing us to, for example, survey all the myelinated axons (the projectome). Further, our reconstructions enabled us to investigate the precise projections of neurons and their contralateral counterparts. In particular, we observed that myelinated axons of reticulospinal and lateral line afferent neurons exhibit remarkable bilateral symmetry. Additionally, we found that fasciculated reticulospinal axons maintain the same neighbour relations throughout the extent of their projections. Furthermore, we use the dataset to set the stage for whole-brain comparisons of structure and function by co-registering functional reference atlases and in vivo two-photon fluorescence microscopy data from the same specimen. We provide the complete dataset and reconstructions as an open-access resource for neurobiologists and others interested in the ultrastructure of the larval zebrafish. ER -