Circuit Diagrams

Abstract Noninvasive tools capable of selectively manipulating neural systems in the human brain are needed to advance our neuroscientific understanding of brain function and develop novel non-pharmacologic psychotherapeutics and are a major focus of Brain Initiative funding. Transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS) modulate neural activity based on inducing electric fields in the brain.

Project Summary/Abstract Our project will create a computational resource, the Single Neuron Analyzer, to support the neuroscience community’s efforts to build a reproducible, comprehensive, data-driven atlas of brain cell types.

ABSTRACT / SUMMARY New technologies are enabling molecular profiling of single brain cells at remarkable throughput. However, these new methods have yet to be extensively applied to the brains of model organisms that bridge the evolutionary distance between mouse and human, including the most common nonhuman primate model system - the rhesus macaque. Here we propose to generate an anatomically resolved, single cell atlas of the epigenome (5.5 million cells) and transcriptome (11 million cells) of the rhesus macaque brain.

Single cell RNA-Seq (scRNA-Seq) and Imaging Transcriptomics (IT) methods have put a systematic understanding of the brain and brain diseases through comprehensive 3-dimensional map of its constituent cell types within reach. However, scRNA-Seq lacks spatial information, whereas Imaging Transcriptomics methods do not yet collect at transcriptome scale and are hampered by throughput.

Single cell isoform expression across mouse brain regions and development Much of the mouse brain's biology is defined by the action of long RNA and protein isoforms in distinct cell types and brain regions. RNA-isoforms are altered on individual variable sites [transcription start site (TSS)- choice, alternative exon inclusion, RNA-modifications and polyA-site choice] during development.

Summary/Abstract The cerebral cortex contains an astonishing diversity of neuronal cell types distributed across dozens of functional areas, which emerge during early development for an apparently uniform neuroepithelium, and the radial glia cells, which act as neural stem cells. Neurogenesis in the cortex follows highly orchestrated and carefully controlled programs that establish a highly reproducible patterns of the six cortical layers.

Project Summary System-wide analysis of cell types in the brain is essential for understanding how complex cellular interactions give rise to various brain functions. Rapidly evolving tissue transformation and clearing technologies have enabled three-dimensional (3D) imaging and phenotyping of intact brains at unprecedented resolution. In particular, proteomic imaging techniques can provide multiscale anatomical, morphological, molecular, and functional information in both non-human and human brains.

ABSTRACT Experimental access to specific cell classes or types in the brain is essential for elucidating their roles in neural circuit function. Single cell transcriptomics has enabled unprecedented definition of cell types at the molecular level and has uncovered numerous marker genes, which can be used to generate genetic tools for access to specific cell populations. However, high-precision genetic tools for experimental access to specific cell-types still rely on genome modification and subsequent crossing of animals harboring different transgenes to generate experimental animals.

Abstract  Understanding the exact cell-­type composition in the different regions of the human brain is a fundamental step  when trying to integrate physiological, behavioral, neurochemical and molecular data. At present, although  major categories of cell-­types present in the human brain have been defined through a handful of specific  markers, the

Project Summary Approximately, 40% of TBI patients discharged from the hospital will develop long-term disability with 70% experiencing chronic cognitive impairments that disrupt vocational, social, and emotional functioning. To foster the reentry of people with severe to moderate traumatic brain injury (smTBI) back into society, as envisioned by the Americans with Disabilities Act, we need to understand the opportunities and challenges posed by cognitive restoration.