权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

From Optogenetic Functional MRI to Mechanogenetic Functional Ultrasound

从光遗传学功能 MRI 到机械遗传学功能超声

基本信息

批准号：
10237358
负责人：
Jin Hyung Lee
金额：
$ 110.39万
依托单位：
STANFORD 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：
2019-09-30 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10237358
关键词：
3-Dimensional Address Algorithms Alzheimer&apos s disease related dementia Animals Award Behavior Behavior Control Behavioral Brain Brain Diseases Brain imaging Cells Complex Computer Models Data Development Electrical Engineering Engineering Functional Magnetic Resonance Imaging Goals Head Human Image Imaging technology Implant Ion Channel Measurement Measures Mechanics Monitor Neurons Neurosciences Operative Surgical Procedures Optics Output Pain Pain management Population Resolution Reverse engineering Specificity Technology Ultrasonography Work awake brain cell cell type flexibility imaging capabilities miniaturize nervous system disorder neuroregulation new technology novel strategies opioid epidemic optogenetics real-time images spatiotemporal success technology development therapy design translation to humans ultrasound

项目摘要

Project Summary / Abstract: Many neuroscience studies have shown that specific cell types within a brain network have unique contributions to behavioral output and that even a single neuron makes connections to large portions of the brain. Therefore, in order to truly get at the problem of uncovering brain function we need measurements with cellular specificity across the whole brain during behavior. As such, due to technological limitations, our current understanding of global brain circuit mechanisms is extremely limited. My recent development of optogenetic functional magnetic resonance imaging (ofMRI) technology provides a partial solution. However, challenges still remain: how do you non-invasively deliver cell type specific neuromodulation? How do you image the whole brain function in freely moving subjects? In this Pioneer Award proposal, I propose a novel approach that enables non-invasive, cell type specific, whole mammalian brain imaging in freely moving subjects. In particular, we propose to develop a non-invasive cell type specific stimulation in mammalian brain termed “Mechanogenetics” and a functional ultrasound (fUS) imaging technology that can image whole brain function in awake-behaving animals. Mechanogenetics will utilize mechanosensitive ion channels expressed in selective cell types enabling neuromodulation using mechanical deflection from ultrasound probes delivered non-invasively instead of using optical probes that need to be surgically implanted. For imaging, miniaturized functional ultrasound technologies with high-resolution, 3D real-time imaging capability that can be mountable on the subject's head will be developed. The resulting “Mechanogenetic functional ultrasound (MfUS)” technology will enable non-invasive flexible modulation of neuronal populations while the impact of such modulation can be monitored in freely moving animals across the whole brain with high spatiotemporal resolution. Instead of measuring large-scale neuronal activity associated with binary behavioral readout or complex behaviors related to single neuronal populations, my goal is to establish a new paradigm for understanding brain function, where cell type specific whole brain function during behavior can be monitored continuously. With such data, combined with computational modeling, whole brain algorithms of behavioral control can be constructed. Furthermore, the Mechanogenetics technology can bring cell type specific neuromodulation closer to human translation. Functional ultrasound technology development will also enable human brain function monitoring in non-laboratory settings. This will ultimately enable brain circuits to be engineered the way electrical engineers engineer electronic circuits allowing direct treatment of neurological disease including Alzheimer's disease and related dementias or directly manage pain addressing the opioid crisis.

项目摘要/摘要：