Ultrasonic Neuromodulation and Sonogenetics: A New Era for Neural Modulation

Wang, Songyun; Meng, Weilun; Ren, Zhongyuan; Li, Binxun; Zhu, Tongjian; Chen, Hui; Wang, Zhen; He, Bo; Zhao, Dongdong; Jiang, Hong

doi:10.3389/fphys.2020.00787

Cited by 39 publications

(33 citation statements)

References 108 publications

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Ultrasound has been used to non-invasively manipulate neuronal functions in humans andother animals 1-4 . However, this approach is limited as it has been challenging to target specific cells within the brain or body [5][6][7][8] . Here, we identify human Transient Receptor Potential A1 (hsTRPA1) as a candidate that confers ultrasound sensitivity to mammalian cells.

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mentioning

confidence: 99%

Sonogenetic control of mammalian cells using exogenous Transient Receptor Potential A1 channels

Duque

Lee-Kubli

Tufail

et al. 2020

Preprint

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Our understanding of the nervous system has been fundamentally advanced by light- and small molecule-sensitive proteins that can be used to modify neuronal excitability. However, optogenetics requires invasive instrumentation while chemogenetics lacks temporal control. Here, we identify a candidate channel that confers sensitivity to non-invasive ultrasound on millisecond timescales. Using a functional screen, we find that human Transient Receptor Potential A1 (hsTRPA1) increases ultrasound-evoked intracellular calcium levels and membrane potentials. Ultrasound, but not agonist, -evoked, gating of hsTRPA1, requires the N-terminal tip region, intact actin cytoskeleton, and cholesterol, implicating these features in the sonogenetic mechanism. We then use calcium imaging and electrophysiology to confirm that ultrasound-evoked responses of primary neurons are potentiated by hsTRPA1. We also show that unilateral expression of hsTRPA1 in mouse layer V motor cortical neurons leads to ultrasound-evoked contralateral limb responses to ultrasound delivered through an intact skull. Finally, ultrasound induces c-fos in hsTRPA1-expressing neurons, suggesting that our approach can be used for targeted activation of neural circuits. Together, our results demonstrate that hsTRPA1-based sonogenetics can effectively and non-invasively modulate neurons within the intact mammalian brain, a method that could be extended to other cell types across species.

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confidence: 99%

Sonogenetic control of mammalian cells using exogenous Transient Receptor Potential A1 channels

Duque

Lee-Kubli

Tufail

et al. 2020

Preprint

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“…This phenomenon has been studied for some time within the context of ultrasound neural modulation (UNM), 306 − 311 yet recently a new approach that combines genetic engineering with UNM has opened new possibilities to control cell function in organisms using ultrasound. 307 , 311 , 312 This approach, known as sonogenetics, is an acoustic analogue of optogenetics and chemogenetics, where cellular function is controlled using light and chemical signals, respectively. Sonogenetics, however, has the unique potential of not requiring light or the diffusion of drugs throughout the body, since, unlike light and small molecules, ultrasound can readily penetrate deep into tissue.…”

Section: Acoustic Responses For Smart Materialsmentioning

confidence: 99%

Ultrasound-Responsive Systems as Components for Smart Materials

et al. 2021

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Smart materials can respond to stimuli and adapt their responses based on external cues from their environments. Such behavior requires a way to transport energy efficiently and then convert it for use in applications such as actuation, sensing, or signaling. Ultrasound can carry energy safely and with low losses through complex and opaque media. It can be localized to small regions of space and couple to systems over a wide range of time scales. However, the same characteristics that allow ultrasound to propagate efficiently through materials make it difficult to convert acoustic energy into other useful forms. Recent work across diverse fields has begun to address this challenge, demonstrating ultrasonic effects that provide control over physical and chemical systems with surprisingly high specificity. Here, we review recent progress in ultrasound–matter interactions, focusing on effects that can be incorporated as components in smart materials. These techniques build on fundamental phenomena such as cavitation, microstreaming, scattering, and acoustic radiation forces to enable capabilities such as actuation, sensing, payload delivery, and the initiation of chemical or biological processes. The diversity of emerging techniques holds great promise for a wide range of smart capabilities supported by ultrasound and poses interesting questions for further investigations.

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“…Pulses can vary in length and are repeated periodically at a given frequency (repetition per second), which determines the duty-cycle (DC) of the US application [14] (Figure 1). [24]).…”

Section: Physics Of Ultrasound and Its Biological Effectsmentioning

confidence: 99%

Drug Delivery by Ultrasound-Responsive Nanocarriers for Cancer Treatment

Entzian

Aigner

2021

Pharmaceutics

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Conventional cancer chemotherapies often exhibit insufficient therapeutic outcomes and dose-limiting toxicity. Therefore, there is a need for novel therapeutics and formulations with higher efficacy, improved safety, and more favorable toxicological profiles. This has promoted the development of nanomedicines, including systems for drug delivery, but also for imaging and diagnostics. Nanoparticles loaded with drugs can be designed to overcome several biological barriers to improving efficiency and reducing toxicity. In addition, stimuli-responsive nanocarriers are able to release their payload on demand at the tumor tissue site, preventing premature drug loss. This review focuses on ultrasound-triggered drug delivery by nanocarriers as a versatile, cost-efficient, non-invasive technique for improving tissue specificity and tissue penetration, and for achieving high drug concentrations at their intended site of action. It highlights aspects relevant for ultrasound-mediated drug delivery, including ultrasound parameters and resulting biological effects. Then, concepts in ultrasound-mediated drug delivery are introduced and a comprehensive overview of several types of nanoparticles used for this purpose is given. This includes an in-depth compilation of the literature on the various in vivo ultrasound-responsive drug delivery systems. Finally, toxicological and safety considerations regarding ultrasound-mediated drug delivery with nanocarriers are discussed.

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Ultrasonic Neuromodulation and Sonogenetics: A New Era for Neural Modulation

Cited by 39 publications

References 108 publications

Sonogenetic control of mammalian cells using exogenous Transient Receptor Potential A1 channels

Sonogenetic control of mammalian cells using exogenous Transient Receptor Potential A1 channels

Ultrasound-Responsive Systems as Components for Smart Materials

Drug Delivery by Ultrasound-Responsive Nanocarriers for Cancer Treatment

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