Informatics

This proposal will disseminate FlyWire, a Drosophila whole brain connectomics resource. We used advances in AI to segment all neurons from a whole brain EM volume called FAFB. The automated segmentation is of high enough quality that, in combination with innovative proofreading tools, scientists can relatively quickly proofread circuits of interest. The community of current collaborators includes about 160 scientists from 40 labs, who have so far succeeded at proofreading more than 15% of the neurons in the fly brain. Several publications have resulted, and more are on the way.

The goal of this project is to disseminate MAPseq and BARseq to the broader neuroscience community. These are novel methods developed in my laboratory based on high-throughput DNA sequencing for determining neuronal circuitry. Neurons transmit information to distant brain regions via long-range axonal projections. In some cases, functionally distinct populations of neurons are intermingled within a small region.

We propose to create VOrtex, a Virtual Observatory for the Cortex: Spanning the Scales of Organelles, Cells, Circuits, and Dynamics. The observatory will disseminate an existing dataset: an automated reconstruction of all cells in a cubic millimeter of mouse visual cortex, along with the synaptic connectivity of the neurons and calcium-imaged responses to video stimuli. The cubic millimeter volume spans all layers of cortex and four visual areas (V1, LM, AL, RL). A team of human proofreaders will detect and correct the remaining errors in the automated segmentation.

We plan to provide software support services for Neuropixels probes, a groundbreaking new tool for recording electrical signals from the brain. These probes—which were created by IMEC, a world-renowned nanoelectronics research center, in collaboration with four funding agencies (HHMI, Allen Institute, Gatsby Foundation, and Wellcome Trust)—will become publicly available in July 2018. Each device consists of a single hair-like shank containing nearly 1000 recording sites, each of which can measure voltage changes with sub-millisecond precision.

The goal of this proposal is to disseminate high resolution large volume serial section electron microscopy data to neuroscientists. Using our electron microscopy facility, we will provide user training on the use of these new technologies and provide access to our specialized facilities so that they may generate permanent ultrathin sections and create data sets amenable for neural circuit analysis or neural and glial cell type analysis.

The central nervous system (CNS) changes throughout life, and its interactions with the world produce activity- dependent plasticity that enables it to acquire and maintain useful behaviors. Recent scientific and technical advances support the development of systems that create novel interactions with the CNS that can induce and guide beneficial plasticity.

Two-photon laser scanning microscopy powers many projects in the.

Recombinant Immunolabels for Nanoprecise Brain Mapping Across Scales Understanding brain function and dysfunction requires an understanding of the circuitry of the brain from molecules to cells to circuits. While no single technique can achieve this, a strategic combination of techniques applied across scales can provide information that when integrated can lead to a more complete picture.

Understanding the function of the nervous system requires a sophisticated understanding of its main output, behavior. Although our ability to record from and to manipulate neurons and neural circuits has accelerated at a spectacular pace over the last decade, progress has lagged in coupling the interrogation of the nervous system to similarly high-resolution measures of behavior.

ABSTRACT Morphology is an essential phenotype in the characterization of cells and their states. It reflects the progression of functional cellular processes, such as morphogenesis, migration, or dendrite arborization, and can be indicative of disease. Delineating the molecular pathways that underlie morphological phenotypes is critical to understanding the relation between genetic pathways, morphology, and function of cells in the brain.