Focused ultrasound neuromodulation on a multiwell MEA

Saccher, Marta; Kawasaki, Shinnosuke; Onori, Martina Proietti; Woerden, Geeske M. van; Giagka, Vasiliki; Dekker, R.

doi:10.1186/s42234-021-00083-7

Cited by 3 publications

(3 citation statements)

References 34 publications

(23 reference statements)

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“…The limitation on quantitative measurement of ultrasound pressure in standing wave conditions can be addressed by a combination of simulation and optical methods. 45,46) Ultrasound stimulation with 39.5 and 500 kHz evoked Ca 2+ concentration changes inside neurons [Fig. 3(a), ] and it was similar to previously reported in vivo neuromodulation studies using sub-MHz ultrasound, where higher intensities were required for high-frequency stimulation.…”

Section: Discussionsupporting

confidence: 84%

Acoustic frequency-dependent physical mechanism of sub-MHz ultrasound neurostimulation

Fan¹,

Shimba²,

Ishijima³

et al. 2022

Jpn. J. Appl. Phys.

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Ultrasound allows non-invasive and reversible modulation of neural circuit activity with high spatial resolution. Despite growing interest in clinical applications, the safe and effective use of ultrasound neuromodulation has been limited by a lack of understanding of the physical mechanisms underlying its effects. Here, we demonstrate acoustic frequency-dependent physical effects that underlie ultrasound neuromodulation, where cavitation and radiation forces are the dominant sources of low- and high-frequency stimulation, respectively. We used 39.5 kHz and 500 kHz acoustic frequencies to stimulate cultured neural and glial cells to study acoustic frequency-dependent neural responses. We demonstrate increased evoked responses due to increased cavitation activity at the 39.5 kHz acoustic frequency. In contrast, notable cavitation activity was not detected at 500 kHz despite detection of evoked responses. Our work highlights the dependence of ultrasound neuromodulation on acoustic frequencies, with different physical effects underlying cell responses to low and high sub-MHz acoustic frequency ranges.

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Section: Discussionsupporting

confidence: 84%

Acoustic frequency-dependent physical mechanism of sub-MHz ultrasound neurostimulation

Fan¹,

Shimba²,

Ishijima³

et al. 2022

Jpn. J. Appl. Phys.

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“…Interestingly, the transient increase in neuronal activity we observed with the chemical PIEZO1 agonist, Yoda1, bears a resemblance to the reported effects of persistent low-frequency ultrasound on cultured hippocampal neurons cultured on microelectrode arrays. Saccher and colleagues reported that persistent exposure to focused ultrasound produced transient elevations in spontaneous network activity [ 54 ]. Calcium imaging studies offer a link between the effects of ultrasound stimulation and mechanosensitive channels, including but not limited to PIEZO1 channels [ 18 , 19 ].…”

Section: Discussionmentioning

confidence: 99%

In Vitro Pharmacological Modulation of PIEZO1 Channels in Frontal Cortex Neuronal Networks

Haghighi,

Schaub,

Shebindu

et al. 2024

Brain Sciences

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PIEZO1 is a mechanosensitive ion channel expressed in various organs, including but not limited to the brain, heart, lungs, kidneys, bone, and skin. PIEZO1 has been implicated in astrocyte, microglia, capillary, and oligodendrocyte signaling in the mammalian cortex. Using murine embryonic frontal cortex tissue, we examined the protein expression and functionality of PIEZO1 channels in cultured networks leveraging substrate-integrated microelectrode arrays (MEAs) with additional quantitative results from calcium imaging and whole-cell patch-clamp electrophysiology. MEA data show that the PIEZO1 agonist Yoda1 transiently enhances the mean firing rate (MFR) of single units, while the PIEZO1 antagonist GsMTx4 inhibits both spontaneous activity and Yoda1-induced increase in MFR in cortical networks. Furthermore, calcium imaging experiments revealed that Yoda1 significantly increased the frequency of calcium transients in cortical cells. Additionally, in voltage clamp experiments, Yoda1 exposure shifted the cellular reversal potential towards depolarized potentials consistent with the behavior of PIEZO1 as a non-specific cation-permeable channel. Our work demonstrates that murine frontal cortical neurons express functional PIEZO1 channels and quantifies the electrophysiological effects of channel activation in vitro. By quantifying the electrophysiological effects of PIEZO1 activation in vitro, our study establishes a foundation for future investigations into the role of PIEZO1 in neurological processes and potential therapeutic applications targeting mechanosensitive channels in various physiological contexts.

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“…To study more complex network responses, a higher-channel density MEA system must be designed to improve its sensitivity 18 . Several future directions for this proposed system have been identified, including using a 3D gantry to hold the transducer and ensure accurate placement 19 . Additional improvements could be made regarding the post-processing algorithm, including utilizing a spiking sorting algorithm 20 In conclusion, this system provides a high-throughput, in vitro platform for studying the neuro-modulatory effects of FUS on human neurons.…”

Section: Parameter Valuementioning

confidence: 99%

Focused Ultrasound Neuromodulation of Human <em>In Vitro</em> Neural Cultures in Multi-Well Microelectrode Arrays

Liang,

Mess,

Punnoose

et al. 2024

JoVE

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The neuromodulatory effects of focused ultrasound (FUS) have been demonstrated in animal models, and FUS has been used successfully to treat movement and psychiatric disorders in humans. However, despite the success of FUS, the mechanism underlying its effects on neurons remains poorly understood, making treatment optimization by tuning FUS parameters difficult. To address this gap in knowledge, we studied human neurons in vitro using neurons cultured from humaninduced pluripotent stem cells (HiPSCs). Using HiPSCs allows for the study of humanspecific neuronal behaviors in both physiologic and pathologic states. This report presents a protocol for using a high-throughput system that enables the monitoring and quantification of the neuromodulatory effects of FUS on HiPSC neurons. By varying the FUS parameters and manipulating the HiPSC neurons through pharmaceutical and genetic modifications, researchers can evaluate the neural responses and elucidate the neuro-modulatory effects of FUS on HiPSC neurons. This research could have significant implications for the development of safe and effective FUS-based therapies for a range of neurological and psychiatric disorders.

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Focused ultrasound neuromodulation on a multiwell MEA

Cited by 3 publications

References 34 publications

Acoustic frequency-dependent physical mechanism of sub-MHz ultrasound neurostimulation

Acoustic frequency-dependent physical mechanism of sub-MHz ultrasound neurostimulation

In Vitro Pharmacological Modulation of PIEZO1 Channels in Frontal Cortex Neuronal Networks

Focused Ultrasound Neuromodulation of Human <em>In Vitro</em> Neural Cultures in Multi-Well Microelectrode Arrays

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