EAGER: Neuromodulation in the second near-infrared window

EAGER：第二个近红外窗口的神经调节

• 批准号: 2217582
• 负责人: Guosong Hong
• 金额: $ 30万
• 依托单位: Stanford University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2217582&HistoricalAwards=false
• 关键词: EAGER; Neuromodulation; second; near; infrared

Understanding the full complexity of the brain requires precisely manipulating the activity of specific neurons and observing their responses. One approach to manipulate neurons, which is termed “optogenetics”, uses visible light to activate light-sensitive ion channels on the cell membrane of neurons. Since visible light does not penetrate deep into the brain, this approach usually requires the invasive implantation of an optical fiber, which delivers light of desired wavelengths into the brain. The aim of this EArly-concept Grant for Exploratory Research (EAGER) project is to improve the penetration depth of light for manipulating specific neurons in the brain, thus eliminating the need of an optical fiber and allowing the subject animal to behave freely. The results obtained from this project will enable noninvasive approaches to modulate brain activity through the intact scalp and skull. This project will also include research training opportunities for underrepresented minority (URM) high school students, with efforts to guide their pursuit of careers in STEM-related work.Understanding neural computation requires causal manipulation of neural activity to dissect the complex circuit connections and the relationship between neural activity and certain behaviors. Optogenetics enable precise modulation of neural activity with millisecond temporal resolution and neuron-type specificity. Conventional optogenetics is performed in the visible spectrum; however, the delivery of visible light usually requires invasive implantation of an optical fiber into the brain, due to light attenuation (i.e., scattering and absorption) in cranial bone and brain tissue. This tethered fiber interface usually leads to acute tissue damage, chronic immune responses, and restriction of the subject’s free behavior. To address these challenges, the Investigator aims to investigate the feasibility of in vivo neuromodulation with light up to 1,500 nm in wavelength in the second near-infrared (NIR-II) spectrum. NIR-II light benefits from much reduced scattering and absorption compared to its visible counterpart, and it has been demonstrated to enable deep-brain imaging through the intact scalp and skull in mice. The Research Plan is organized under three objectives: (1) Synthesize biocompatible polymers with NIR-II absorption in the range of 1,000~1,500 nm; (2) Target NIR-light sensitive transient receptor potential vanilloid 1 (TRPV1) ion channels in dorsal root ganglion (DRG) neurons with NIR-II absorbing polymers for in-vitro neuromodulation; and (3) Demonstrate the feasibility of NIR-II neuromodulation in the mouse hippocampus through the intact scalp and skull. The knowledge gained from this project will shed light on the feasibility of optogenetic neuromodulation in the NIR-II window and thus offer more guidance on NIR-II light-based approaches in biology.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

要了解大脑的全部复杂性，需要精确地操纵特定神经元的活动并观察它们的反应。一种操纵神经元的方法被称为“光遗传学”，它使用可见光来激活神经元细胞膜上的光敏离子通道。由于可见光不会深入大脑，这种方法通常需要侵入性地植入光纤，将所需波长的光传输到大脑中。这个早期概念探索性研究奖助金(AGER)项目的目的是提高光的穿透深度，以操纵大脑中的特定神经元，从而消除对光纤的需要，并允许受试者自由行动。从这个项目中获得的结果将使非侵入性方法能够通过完整的头皮和头骨来调节大脑活动。该项目还将包括为未被充分代表的少数族裔(URM)高中生提供研究培训机会，努力指导他们在STEM相关工作中追求职业生涯。理解神经计算需要对神经活动进行因果操作，以剖析复杂的电路连接以及神经活动和某些行为之间的关系。光遗传学使神经活动的精确调节具有毫秒的时间分辨率和神经元类型的特异性。传统的光遗传学是在可见光光谱中进行的；然而，由于颅骨和脑组织中的光衰减(即散射和吸收)，传输可见光通常需要在大脑中植入光纤。这种栓系的纤维界面通常会导致急性组织损伤、慢性免疫反应和受试者自由行为的限制。为了应对这些挑战，研究人员旨在研究在第二近红外(NIR-II)光谱中利用波长长达1,500 nm的光进行体内神经调节的可行性。与可见光相比，NIR-II光的散射和吸收大大减少，并已被证明能够通过小鼠完整的头皮和头骨进行深部大脑成像。该研究计划分为三个目标：(1)合成在1,000~1,500 nm范围内具有NIR-II吸收的生物相容性聚合物；(2)利用NIR-II吸收聚合物制备靶向近红外光敏瞬时受体电位香草素1(TRPV1)离子通道，用于体外神经调节；(3)证明通过完整的头皮和颅骨对小鼠海马区进行NIR-II神经调制的可行性。从这个项目中获得的知识将阐明在NIR-II窗口进行光遗传神经调节的可行性，从而为NIR-II在生物学中基于光的方法提供更多指导。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Nanotransducer-Enabled Deep-Brain Neuromodulation with NIR-II Light

• DOI: 10.1021/acsnano.2c12068
• 发表时间: 2023-04-20
• 期刊: ACS NANO
• 影响因子: 17.1
• 作者: Wu，Xiang;Yang，Fan;Hong，Guosong
• 通讯作者: Hong，Guosong