Noninvasive, ultrasound-mediated viral delivery of genes for optogenetic study of brain function

无创、超声介导的病毒基因传递用于脑功能的光遗传学研究

• 批准号: BB/R022437/1
• 负责人: Simon Schultz
• 金额: $ 19.28万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FR022437%2F1
• 关键词: Noninvasive; ultrasound; mediated; viral; delivery

Optogenetics - genetically modifying cells to make them light-sensitive, in order to read and write signals into the brain - has revolutionised neuroscience. The ability to imprint particular patterns of neural activity into the brain, and to observe signalling in networks of brain cells during behaviour, is already bringing substantial new understanding of topics such as memory, perception and movement. In the longer term, it also offers us new ways to interface with the brain, to repair or enhance brain function. However, at the moment, the use of optogenetic techniques requires a highly invasive procedure: direct injection of viral vectors into the nervous system. In this project, we will develop and optimise a technology which promises to replace this intracerebral injection with a much less invasive approach: intravenous injection of the vector, followed by delivery of the genes across the blood-brain barrier by using specially tailored sequences of fast ultrasound pulses. If successful, this will mean that many neuroscience experiments that currently require surgical intervention will be able to be carried out almost entirely non-invasively. It will also result in new neuroscience techniques being much more translatable to human studies, as ultrasound can be safely carried out in human subjects.

光遗传学--对细胞进行遗传修饰，使其对光敏感，以便将信号读取和写入大脑--已经彻底改变了神经科学。将特定的神经活动模式印入大脑，以及观察行为过程中脑细胞网络中的信号传递的能力，已经为记忆、感知和运动等主题带来了实质性的新理解。从长远来看，它还为我们提供了与大脑接口的新方法，以修复或增强大脑功能。然而，目前，光遗传学技术的使用需要一个高度侵入性的过程：将病毒载体直接注射到神经系统中。在这个项目中，我们将开发和优化一种技术，该技术有望用一种侵入性更小的方法取代这种脑内注射：静脉注射载体，然后通过使用专门定制的快速超声脉冲序列将基因传递穿过血脑屏障。如果成功，这将意味着许多目前需要手术干预的神经科学实验将能够几乎完全非侵入性地进行。这也将导致新的神经科学技术更容易转化为人类研究，因为超声可以安全地在人类受试者中进行。

项目成果

A computational grid-to-place-cell transformation model indicates a synaptic driver of place cell impairment in early-stage Alzheimer's Disease.

• DOI: 10.1371/journal.pcbi.1009115
• 发表时间: 2021-06
• 期刊: PLoS computational biology
• 影响因子: 4.3
• 作者: Ness N;Schultz SR
• 通讯作者: Schultz SR

All-optical crosstalk-free manipulation and readout of Chronos-expressing neurons.

Chronos 表达神经元的全光学无串扰操纵和读出。

• DOI: 10.1088/1361-6463/aaf944
• 发表时间: 2019
• 期刊: Applied physics
• 作者: Soor NS

Place Cells in Head-Fixed Mice Navigating a Floating Real-World Environment.

• DOI: 10.3389/fncel.2021.618658
• 发表时间: 2021
• 期刊: Frontiers in cellular neuroscience
• 影响因子: 5.3
• 作者: Go MA;Rogers J;Gava GP;Davey CE;Prado S;Liu Y;Schultz SR
• 通讯作者: Schultz SR

High speed functional imaging with source localized multifocal two-photon microscopy.

• DOI: 10.1364/boe.9.003678
• 发表时间: 2018-08-01
• 期刊: Biomedical optics express
• 影响因子: 3.4
• 作者: Quicke P;Reynolds S;Neil M;Knöpfel T;Schultz SR;Foust AJ
• 通讯作者: Foust AJ

Subcellular resolution 3D light field imaging with genetically encoded voltage indicators

• DOI: 10.1101/2020.05.22.108191
• 发表时间: 2020-05
• 期刊: bioRxiv
• 作者: Peter Quicke;Carmel L. Howe;P. Song;H. V. Jadan;Chenchen Song;T. Knöpfel;M. Neil;P. Dragotti