Cooperative Agreements

Cell atlas of mouse brain-spinal cord connectome

PROJECT SUMMARY Although great efforts have been dedicated to characterizing neuronal cell types in the brain, systematic studies on the brain-spinal cord connectome and associated spinal neuronal types are lacking. In this project, a team of seven laboratories proposes to use a highly innovative and multidisciplinary approach to systematically characterize neuronal types in the spinal cord based on their anatomy, connectivity, neuronal morphologies, molecular identities, and electrophysiological properties.

Toward a human adult brain cell atlas with single-cell technologies

Abstract Human brain is an exceedingly complex network of spatially organized and functionally connected neurons imbedded in glia. In surpasses the mouse brain by three orders of magnitude in terms of sheer numbers of cells, and likely has a more complex organization structure relevant to human-specific cognitive functions. Defining a complete cell atlas of the human brain, including a full catalog of all cell types (i.e.

Towards integrated 3D reconstruction of whole human brains at subcellular resolution

Project Summary A detailed understanding of the anatomical and molecular architectures of brain cells and their brain-wide organization is essential for interrogating human brain function and dysfunction. Extensive efforts have been made toward mapping brain cells through various lenses, which have established invaluable databases yielding new insights. However, integrative extraction of the multimodal properties of various cell-types brain-wide within the same brain, crucial to elucidating complex intercellular relationships, remains nearly impossible.

Dendritome mapping of genetically-defined and sparsely-labeled cortical and striatal projection neurons

PROJECT SUMMARY Integrating molecular, morphological, and connectomic properties is critical for unbiased classification of neuronal cell types in the mammalian brain. Here we propose a novel approach to classify neuronal cell types by brainwide comprehensive profiling of the dendritic morphology of genetically-defined neurons in the mouse brain. We have developed an innovative mouse genetic tool, called Mosaicism with Repeat Frameshift (or MORF), which enables sparsely and stochastically labeling of genetically-defined neurons in mice.

Engineered viral tropism for cell-type specific manipulation of neuronal circuits

 DESCRIPTION (provided by applicant): It is a longstanding goal in neuroscience to reveal how specific cell types contribute to different neural circuits that underlie cognition, behavior, and disease pathology. Although cell types can be grouped into descriptive categories (excitatory, inhibitory, peptidergic etc.), we know there is a great combinatorial diversity of cels that differ in ion channel and receptor expression levels and fulfill discrete roles within neural circuits.

LIPS: A novel technology for spatial and temporal control of protein synthesis in dendritic spines

 DESCRIPTION (provided by applicant): The proteins in synapses are the fundamental regulators of synaptic plasticity, which ultimately controls the neural circuits that underlie behavior. A major advance in our understanding of how synaptic connectivity is linked to animal behavior comes from transcranial two-photon imaging of dendritic spines in living animals. However, despite the advances made by two-photon microscopy, most experiments have been observational.

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