Research Projects

Project Summary Multiplexed imaging of brain cells and tissues can reveal critical details about the abundance and spatial organization of molecular targets. Sequential imaging methods based on iterative labeling and imaging enables practical higher multiplexing, but generally require complex fluidic setup with multiple rounds of slow buffer exchange. We propose to develop the thermal-plex method which removes complex and slow buffer exchange steps, and provides a fluidic-free, rapid sequential imaging method.

SUMMARY The brain is composed of thousands of highly specialized cell types that form very specific synaptic connections with each other. Together, these connections form neural circuits that are the structural basis of brain function. Despite their importance, synaptic connections amongst cell types are largely unascertained, because of the dearth of existing tools to do so.

ABSTRACT Understanding the function of neural circuits requires thorough investigation of two circuit elements: cell types and connectivity. The combination of axonal tracing with high-throughput DNA sequencing of genetically barcoded neurons has enabled the simultaneous characterization of anatomical and molecular identities of neurons and their projection fields. However, no high- throughput tools currently exist that allow us to map connections between presynaptic and postsynaptic neurons while identifying the cell types of mapped neurons.

Project Summary To determine the anatomical basis of complex neural behavior, it is critical to have the ability to trace more than one circuit simultaneously in the same animal. That’s because complex animal behaviors or neural computation should be understood through the interaction of more than one circuit – cooperative, antagonistic, or else. In addition, it is necessary to rapidly capture the connectivity information in the dynamically changing brains during development and learning.

Summary The goal of this proposal is to develop DDALAB, a software platform that will make it possible for researchers to identify latent cortical states and analyze the flow of information in large populations of neurons using Delay Differential Analysis (DDA). Although DDA can be used to analyze any time series data, we will initially focus on EEG recordings from the scalp and iEEG data recordings directly from the brain.

PROJECT SUMMARY / ABSTRACT The BRAIN Initiative’s -omics data archive NeMO contains all the BICCN single cell single cell data, more than one million files at the time of writing.

cloudSLEAP – PROJECT SUMMARY/ABSTRACT Understanding how the brain produces complex behavior is a central goal of neuroscience, but quantifying behavior is technically challenging, particularly in unrestrained and naturalistic settings. Tools that are able to overcome these limitations leverage deep learning to achieve robust markerless motion capture, enabling characterization of behavior through precise positional tracking of body parts from standard videos of behavior.

Summary: Behavioral data is central to biomedical research, including both synchronous measures (e.g. brain activation and button-presses from a reading task in an fMRI scan), and those performed independently (e.g. a literacy questionnaire.) Compared to neurophysiology and brain imaging data, behavioral data is often relatively small, with file sizes in the megabytes rather than terabytes for both experimental scripts and resulting datasets.

PROJECT SUMMARY Neuromodulation, such as that mediated by the neuromodulators norepinephrine, acetylcholine, and dopamine, imposes powerful control over brain function. It regulates the excitability, synaptic plasticity, and other aspects of neuronal function. Defects in neuromodulation are associated with many neuropsychiatric diseases. Neuromodulators exert their functions by regulating intracellular signaling events via their corresponding G protein-coupled receptors (GPCRs).

Project summary The heterogeneity from the vast number of cell types in the brain presents a major challenge in our understanding of how brain works and in our treatment of neurological disorders. With the amazing advances in high throughput sequencing technology, our knowledge on the molecular makeup of the myriad cell types in the brain has reached an unprecedented level. However, tools that allow us to easily study the functions of any cell types of our choice are lagging. The goal of our proposed research is to develop technology to generate such tools.