PROJECT SUMMARY A goal of the BRAIN initiative is to develop and validate novel tools to map and manipulate neural circuits. The definition and control of behaviorally relevant circuits requires both retrograde and anterograde trans-synaptic technologies that perform well in vivo.
Project Summary Neuroscience stands at the precipice of a new depth of understanding about how the brain works thanks to recent advances in imaging data acquisition technologies such as light-sheet fluorescence microscopy (LSFM). How- ever, the lack of analytic tooling to mine this rich information's relationship across samples, timepoints, and data acquisition technologies prevents researchers from unlocking quantitative relationships. We propose the creation of an easy-to-use, distributed-computation image registration tools that will map large images into a common reference frame.
PROJECT SUMMARY Tools for exclusively targeting neuronal and glial subtypes are needed to advance our understanding of the brain. “Intersectional” systems improve targeting by restricting “reporter/effector” transgenes to a subdomain defined by the expression overlap between two activating factors. “Split-driver” systems have enhanced targeting precision in flies and are operable in fish, but have yet to be systematically deployed in vertebrate systems.
Abstract The brain is remarkably complex, and our understanding of this organ is still in its infancy. Many fundamental questions about brain development and function remain. Single cell genomics promises new ways to answer these questions, but nearly all single-cell methods share shortcoming – cells are destroyed when their molecular states are measured.
PROJECT SUMMARY Methods for regulating cellular processes within distinct populations of neurons are needed to elucidate relationships between molecular mechanisms, circuits, and behavior; and to develop cell type- or circuit- selective treatments for neurological disorders. We propose a novel, non-genetic, small molecule method— transcription factor-chemically induced proximity (TF-CiP)—that harnesses the cell type- and circuit-specificity of endogenous transcription factors to regulate gene expression in subsets of neurons.
Project Summary Despite the rapid advances in the neuroimaging research workflow over the last decade, the enormous variability between and within data types and specimens impedes integrated analyses. Moreover, the availability of a comprehensive portfolio of software libraries and tools has also resulted in a concerning degree of analytical variability.
Project Summary The proposed work will address a critical gap in our understanding of neuronal phenotypes and cell types by developing machine learning algorithms and cloud-based software for the integration of multiple modality characterizations large and growing datasets of cortical neurons in mouse and human.
PROJECT SUMMARY/ABSTRACT Modern experimental approaches allow researchers to collect a variety of whole-brain data from the same animal via different anatomical labels, including tracers, genetic markers, and fiducial marks from recording electrodes. Unfortunately, viewing and analysis methods have not kept pace with the complexity of these datasets, which can be as large as several terabytes. This limitation makes it time- and resource-intensive to view and manipulate light-microscopy data or to share these datasets with distant laboratories.
The increasing availability and ease of use of confocal, two-photon, and light-sheet microscopes coupled with rapid developments in fluorescent protein reporters have made 3D and functional imaging and its analysis a central component of modern Neuroscience research. Yet, the ease of acquiring 3D and functional images is creating progressively larger datasets, prompting the need for high-throughput image analysis algorithms and software that can be both rapid and accurate.
Project Summary Neural prosthetic devices for sensorimotor and psychiatric disorders are in development as a priority area of the BRAIN Initiative yet they raise important ethical concerns about human agency.
