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Functional and cell-type specific axonal pathways in the primate brain

灵长类动物大脑中的功能和细胞类型特异性轴突通路

基本信息

批准号：
10272370
负责人：
R CLAY REID
金额：
$ 153.57万
依托单位：
ALLEN INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10272370
关键词：
Alzheimer&apos s disease patient Anatomy Antibodies Area Atlases Autopsy Axon BRAIN initiative Biological Assay Brain Brain Diseases Calcium Cells Censuses Classification Data Data Set Development Diffusion Magnetic Resonance Imaging Disease Marker Electrodes Functional Imaging Functional Magnetic Resonance Imaging Genes Goals Histologic Human Image Individual Institutes Institution Label Macaca Magnetic Resonance Imaging Maps Measures Methodology Methods Modality Molecular Neurodegenerative Disorders Neurons Neurosciences Optics Parietal Pathway interactions Phase Physiology Play Population Primates Program Appropriateness Property Prospective Studies Protocols documentation RNA RNA Probes Recording of previous events Research Resolution Role Specificity Stream Surface Techniques Technology Testing Tissues Translating United States National Institutes of Health Visual Cortex Visual system structure Work anatomic imaging brain cell brain tissue brain volume cell type experimental study human tissue improved in vivo innovation light microscopy multimodality multiphoton imaging neural circuit neuromechanism nonhuman primate novel optical imaging postsynaptic programs relating to nervous system success tool transcriptomics white matter

项目摘要

Project Summary/Abstract Over the past decade, there have been transformative advances in three areas of mammalian neuroscience. First, our ability to record from large populations of neurons has dramatically increased with the advent of new electrode technologies and improved multiphoton imaging. Second, the study of brain connections in their entirety, connectomics, has come into its own as a field. Most recently, there has been a revolution in the classification of neuronal types, largely by probing which genes are translated into RNA in cells (transcriptomics). What is lacking is a way to bring these three fields together, particularly in the studies of non-human primates and humans. The goal of the current RFA is to create innovative tools for use in humans and non-human primates. In particular, two suggested topics are to develop: (1) “novel methods for tagging individual neurons such that cellular components of a functional circuit can be explored” and (2) “innovative approaches to bridge scales of experimental approach. Studies that can explore molecular and cellular mechanisms of neural activity in broader contexts are encouraged.” To achieve these goals, we present an innovative approach to characterize neuronal cell types in macaques and humans, combining transcriptomics, inter-areal connectivity and functional studies at multiple scales, from individual neurons to entire brains. We will build the necessary tools to create integrated atlases of individual brains that combine six modalities into a common reference frame: (1) functional MRI, to measure functional properties of brain areas at 0.5-1 mm resolution, (2) widefield optical imaging, to map bulk neuronal activity at the cortical surface with ~100 µm resolution, (3) multiphoton calcium imaging, to map neuronal activity in individual neurons across multiple cortical areas, (4) diffusion tensor imaging (DTI), to map axonal tracts in the white matter with 0.5-1 mm resolution, (5) “axonal connectomics”, to map projections of individual myelinated axons from efferent cell bodies to their postsynaptic targets, and (6) multiplexed FISH, to assay transcriptomic identities of the same cells whose physiology and projection targets have been defined. Data from first three modalities will be collected, starting with in vivo studies of macaques and correlated with subsequent analysis of brain tissue with the last three modalities. Only the last three steps will be used in the study of human brain tissue, although functional MRI could, in principle, be obtained from research institutions with appropriate programs for prospective studies.

项目总结/文摘