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Related Experiment Video

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Assaying Circuit Specific Regulation of Adult Hippocampal Neural Precursor Cells
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Modulation of deep neural circuits with sonogenetics.

Quanxiang Xian1, Zhihai Qiu1,2, Suresh Murugappan1

  • 1Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR 999077, P.R. China.

Proceedings of the National Academy of Sciences of the United States of America
|May 22, 2023
PubMed
Summary

Scientists developed a new sonogenetic method using ultrasound to control deep brain neurons. This technique precisely targets neural circuits, influencing mouse behavior and showing potential for treating neurological disorders.

Keywords:
MscL-G22Sneural circuitsneuromodulationsonogeneticsultrasound

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Area of Science:

  • Neuroscience
  • Biotechnology
  • Medical Engineering

Background:

  • Noninvasive control of deep brain neuronal activity is crucial for understanding brain function and treating neurological disorders.
  • Current methods often lack precision or temporal resolution for effective deep brain manipulation.

Purpose of the Study:

  • To develop and validate a sonogenetic approach for noninvasive, circuit-specific control of neuronal activity in the deep brain.
  • To demonstrate the efficacy of this approach in modulating distinct mouse behaviors and alleviating symptoms of neurodegenerative disease.

Main Methods:

  • Utilized a mutant large conductance mechanosensitive ion channel (MscL-G22S) expressed in targeted neurons.
  • Employed ultrasound stimulation to trigger neuronal activity with subsecond temporal resolution.
  • Validated the approach in dorsal striatum, ventral tegmental area, and subthalamic nuclei of mice, including Parkinson's disease models.

Main Results:

  • Ultrasound successfully activated MscL-G22S-expressing neurons, increasing locomotion and modulating the mesolimbic pathway.
  • Sonogenetic stimulation improved motor coordination and mobility in Parkinson's disease model mice.
  • Responses were rapid, reversible, and repeatable, with the MscL-G22S mutant showing higher efficacy than wild-type MscL.

Conclusions:

  • Sonogenetics offers a precise, noninvasive method for manipulating targeted neural pathways and behaviors.
  • This approach holds significant potential for advancing neuroscience research and developing novel therapies for neurological and neurodegenerative diseases.