Seminar:Precise control of neuronal activity by ultrasound: fundamentals and toolkits

Speaker:Dr. Lei Sun

Associate Professor in the Interdisciplinary Division of Biomedical Engineering, 

the Hong Kong Polytechnic University.

Time: 9: 00-10:00am, May 13

Location: Conference Room in Old BME Building

Abstract: Ultrasonic (US) brain stimulation, has been demonstrated to noninvasively alter neuron activity in animals and humans. Capable of non-invasive transmission trough skull with fine focal size (~mm), it is an encouraging means and a good alternative to existing stimulating strategies. However, the bio-effects of US are diverse and thus it is crucial for developing precise neuron control method for later translation. Here we focus on gating mechanosensitive ion channels (MCs) by US and explored as fundamentals for the developing selective US neuron stimulation. 

The cell membrane tension was approximated by various models and then calculate the interaction with MCs. On gating MCs by ultrasound was verified on Piezo1 expressed HEK293t cells and primary cultured neurons. In addition, functional modified nanobubbles targeted neuron was utilized to verify the acoustic mechanogenetics model for MCs activation. Calcium imaging and whole cell patch clamp techniques were utilized to characterize the responses. Based on these proof of concept results, sono- and acoustic mechano-genetic toolkits for neuron activity stimulation and visualization simultaneously were developed.

It is shown that ultrasound can mediate membrane tension which can be tuned up to one order magnitude higher than which for gating MCs, here Piezo 1. The open probability of MCs as a function of acoustic pressure highly depends on frequency, MCs is more sensitive to lower frequency US. Experimental results clearly demonstrated that ultrasound can activate Piezo1-HEK293t cells with calcium influx while no response could be detected for the control cells. The inward current and calcium influx depends on US pressure for Piezo1 overexpressed HEK293T and neurons. On the other hand, the nano-bubble targeted neurons can be activated by low acoustic pressure as well. These results show that ultrasound is able to modulate neuronal activity by gating mechanosensitive ion channels. It demonstrates reliable precise control of neuron activity by ultrasound. The toolkit for sonogenetics and acoustic mechanogenetics are being developed.. 


Biography: Dr. Lei SUN received PhD degree from Pennsylvania State University, and post-doctoral training at University of Southern California. Dr. SUN has developed different techniques and systems and for innovative ultrasound imaging. His recent research interests are ultrasound neuro-modulation, molecular ultrasound/photoacoustic imaging, and novel ultrasound contrast agents. He has published over 80 peer-reviewed journal papers and international conference proceedings.

Dr. Sun received various awards, including faculty research grant achievement award from Hong Kong Polytechnic university, best paper and poster awards from different international conferences. He is the committee member of Medical Ultrasound Engineering Society of Chinese Society of Biomedical Engineering (中国生物医学工程学会医学超声工程分会) and Instrumentation and Device Development Committee of China Association of Ultrasound and Engineering (中国超声医学工程学会仪器开发专业委员会).


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