用于体内显微内窥镜钙成像的基因编码活动传感器单步靶向表达的病毒载体洗脱透镜。

IF 4.4 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Macromolecular bioscience Pub Date : 2024-09-16 DOI:10.1002/mabi.202400359
Carolyn K Jons, David Cheng, Changxin Dong, Emily L Meany, Jonathan J Nassi, Eric A Appel
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引用次数: 0

摘要

研究大脑的光学方法为了解神经活动如何成为复杂行为的基础提供了强有力的方法。这些方法通常依靠基因编码的传感器和致动器来监测和控制神经活动。在微内窥镜钙成像中,需要先注射病毒,然后植入透镜探针,以表达钙传感器,并通过光学方法进入目标脑区。这两个步骤带来了一些挑战,其中最主要的是与病毒表达区、透镜探针和目标脑区之间的误定位和/或错位有关的风险。在这里,为梯度折射率(GRIN)镜片设计了一种腺相关病毒(AAV)洗脱聚合物涂层,可在植入镜片后直接在相关脑区表达基因编码的钙指示剂(GCaMP)。这种方法只需一个手术步骤,并能保证 GCaMP 的表达与透镜在大脑中的位置一致。此外,这些涂层释放病毒的速度很慢,因此增加了手术植入的工作时间,扩大了适合这种方法的大脑区域和物种。这些增强的功能将加速利用光学方法进行的神经科学研究,并促进对大脑功能和健康与疾病行为的神经回路机制的了解。
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Viral Vector Eluting Lenses for Single-Step Targeted Expression of Genetically-Encoded Activity Sensors for in Vivo Microendoscopic Calcium Imaging.

Optical methods for studying the brain offer powerful approaches for understanding how neural activity underlies complex behavior. These methods typically rely on genetically encoded sensors and actuators to monitor and control neural activity. For microendoscopic calcium imaging, injection of a virus followed by implantation of a lens probe is required to express a calcium sensor and enable optical access to the target brain region. This two-step process poses several challenges, chief among them being the risks associated with mistargeting and/or misalignment between virus expression zone, lens probe and target brain region. Here, an adeno-associated virus (AAV)-eluting polymer coating is engineered for gradient refractive index (GRIN) lenses enabling the expression of a genetically encoded calcium indicator (GCaMP) directly within the brain region of interest upon implantation of the lens. This approach requires only one surgical step and guarantees alignment between GCaMP expression and lens in the brain. Additionally, the slow virus release from these coatings increases the working time for surgical implantation, expanding the brain regions and species amenable to this approach. These enhanced capabilities should accelerate neuroscience research utilizing optical methods and advance the understanding of the neural circuit mechanisms underlying brain function and behavior in health and disease.

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来源期刊
Macromolecular bioscience
Macromolecular bioscience 生物-材料科学:生物材料
CiteScore
7.90
自引率
2.20%
发文量
211
审稿时长
1.5 months
期刊介绍: Macromolecular Bioscience is a leading journal at the intersection of polymer and materials sciences with life science and medicine. With an Impact Factor of 2.895 (2018 Journal Impact Factor, Journal Citation Reports (Clarivate Analytics, 2019)), it is currently ranked among the top biomaterials and polymer journals. Macromolecular Bioscience offers an attractive mixture of high-quality Reviews, Feature Articles, Communications, and Full Papers. With average reviewing times below 30 days, publication times of 2.5 months and listing in all major indices, including Medline, Macromolecular Bioscience is the journal of choice for your best contributions at the intersection of polymer and life sciences.
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