Project Summary Estimates of the total length of axonal "wiring" in the human brain are on the order of hundreds of thousands of kilometers. Understanding the fundamental principles underlying the connectivity between cells is a daunt- ing task, but it has become increasingly clear that there are canonical connectivity patterns across the layers of the mammalian cortex.
Summary Functional Magnetic Resonance Imaging data has been a mainstay of neuroscience research for more than two decades, as it allows rapid, continuous, noninvasive monitoring of neuronal function. However, a substantial portion of the fMRI signal arises from purely physiological cerebral hemodynamic signals in the low and cardiac frequency bands.
ABSTRACT Reproducible findings are essential to scientific advancement. Unfortunately, when fields lack consensus standards for methods, or their implementations, reproducibility tends to be more of an ideal than a reality.
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.
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.
