Research Projects

Project Summary The goal of this project is to create a unified framework for understanding the relationship between neuronal gene expression and connectivity in mouse visual cortex, by using morphology as a key linking modality. There now exist publicly available large-scale data sets that measure both these modalities in mouse visual cortex. One dataset is a large set of Patch-seq experiments from single cells, which provide measurements of gene expression, electrophysiological properties and morphology for individual cells.

ABSTRACT The non-human primate (NHP) model is critical to the advancement of translational neuroscience, as it allows researchers to link observations regarding macroscale brain dynamics and cognition in the human to underlying meso- and microscale phenomena that cannot be fully investigated in humans. Importantly, the ultimate value of findings from the NHP for informing human models relies on the adequacy of methods for cross-species anatomical and functional alignment.

SUMMARY Brain-mapping initiatives are acquiring increasingly large and comprehensive neuroimaging and multiomic— e.g. genomic and transcriptomic—datasets. Existing analyses of such data in human neuroscience tend to search for links between cognition, behavior or disease on the one hand, and properties of genomes, transcrip- tomes or brain morphology and connectivity on the other. Such valuable analyses have steadily advanced our knowledge of human brain function.

PROJECT SUMMARY/ABSTRACT The growing availability of large functional magnetic resonance imaging (fMRI) datasets has enabled new investigations into functional systems of the human brain. A challenge – but also opportunity – of fMRI arises from the fact that BOLD signal stems from multiple intertwined neural and physiological sources. One major contributor to fMRI signals arises from slow (

Technology for automating the segmentation of neurons from electron microscopic (EM) data has improved dramatically, making it now possible to obtain accurate reconstructions of neural circuits from large EM volumes. However, even the best automation still must be followed by human proofreading to attain high accuracy. Hundreds of neuroscientists are already using our ChunkedGraph system for proofreading neural circuits. The system is fully web- and cloud-ready, facilitating seamless collaboration.

Project Summary Recent advances in technology driven by the BRAIN Initiative have yielded new methods for characterizing the ac- tivity, transcriptome, and microscale anatomy of neurons throughout the brain, and have increased the throughput of these techniques by orders of magnitude.

This two-year project will advance, integrate, document, and promote the use of the Hierarchical Event Descriptor (HED) system to describe events in human neuroimaging and behavioral data from research experiments and other sources in sufficient detail to support comparative analysis of human brain dynamics across studies. Relating the recorded data dynamics to temporally- specifiable changes in subject experience, action, and cognition is a major goal (and challenge) for both neuroimaging and biomechanical imaging.

ABSTRACT Depicting the specific neuronal identity and connectivity underlying particular brain function remains a central goal for neuroscience. For over a century, neuroanatomy has continued to play critical roles in referencing a neuron's synaptic contact, dendritic morphology and axonal projection to its connectivity. The advances of genetic probes, optical imaging modalities and computer technologies permit monitoring and manipulating neuronal activity in living animals with unprecedented precision and scale.

PROJECT SUMMARY Every part of the brain is composed of dense tangles of heavily-interconnected neurons of many different types, each playing completely different roles in the circuitry. Rabies viral vectors have become indispensable tools for revealing the organization of this otherwise generally indecipherable jumble, because they allow the identification of synaptically-connected networks of neurons within the tissue.

Project Summary The development of trans-synaptic viral tracers is an important component of the BRAIN Initiative. At present, the lack of viral-based anterograde monosynaptic tracing tools with high signal strength and low toxicity is a gap in neuroscience.