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Technology for functional study of cells and circuits in large postmortem brains ex vivo

离体大型死后大脑细胞和电路功能研究技术

基本信息

批准号：
9928247
负责人：
NENAD SESTAN
金额：
$ 15.56万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-01 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9928247
关键词：
Address Algorithms Anatomy Animal Feed Animal Model Animals Area Automation Autopsy Axon Biological Brain Brain region Cardiovascular system Cell physiology Cells Cellular Morphology Cephalic Cerebrum Chemicals Communities Complex Custom Disease Electrocorticogram Electrolytes Electrophysiology (science)Engineering Family suidae Food production Formulation Functional Imaging Functional disorder Gases Genetic Glucose Goals Grant Harvest Health Hippocampus (Brain)Histologic Histology Homeostasis Hour Human Investigation Kinetics Label Lead Maintenance Mammals Mechanics Mental disorders Metabolism Methodology Microcirculation Modeling Molecular Molecular Analysis Molecular Structure Monitor Names Neurons Neurosciences Nutrient Operative Surgical Procedures Output Perfusion Physiologic pulse Physiological Positron-Emission Tomography Pulsatile Flow Quality Control Research Research Personnel Resolution Resuscitation Scanning Source Structure Synapses System Techniques Technology Temperature Time Tissue Viability Tissues Tracer Translations Validation X-Ray Computed Tomography Zoology base brain tissue cell type density experimental study functional outcomes imaging capabilities imaging modality imaging study improved in vivo multimodality neocortical nervous system disorder neural circuit neurotechnology new technology non-genetic novel novel strategies patch clamp preservation pressure prototype relating to nervous system restoration sensor tissue culture tool user-friendly vector

项目摘要

PROJECT SUMMARY The mammalian brain is arguably the most complex biological structure. Investigating cellular functions and mapping neural connections in the brain are critical tasks to better understand the brain in health and disease. This is particularly challenging in vivo due to the inherent limitations in experimental latitude and simultaneous access to multiple brain regions within the same animal. These shortcomings hinder multimodal interrogation of multi-synaptic circuits and mesoscale connectomics. Of particular importance, these experimental inadequacies grow in proportion to the complexity of the brain and cranial anatomy, impeding translation to larger mammals. This grant addresses these tasks by optimizing and validating a first-in-class neurotechnology called BrainEx for the restoration of molecular and cellular functions of the postmortem large mammalian brain under ex vivo, normothermic conditions. We specifically propose to continue optimizing BrainEx in porcine brains, while validating the efficacy of the BrainEx system as a new experimental platform for electrophysiological, connectomic, and imaging studies in the fully isolated, intact, and functional large mammalian brain. There are four major distinguishing aspects of this application: (1) implementation of novel approaches developed to restore cerebral macro- and microcirculation and extend cellular viability of the postmortem brain under normothermic conditions such that researchers can (2) simultaneously trace connections and characterize cellular function and morphology by chemical and vector-based techniques across myriad brain regions, including areas inaccessible to in vivo surgical approaches; (3) investigate multisynaptic long-range circuitry and cortical network electrical activity; and (4) perform functional PET and CT imaging studies in the ex vivo large mammalian brain. This methodology represents a new tool for more thorough investigation of the structure and function of complex circuits and the cells within them. Wide distribution of this technology will grant investigators experimental advantages across species not afforded by tissue culture or in vivo approaches.

项目总结