神经科学
伏隔核
纹状体
脑深部刺激
生物神经网络
丘脑底核
多巴胺
被盖腹侧区
刺激
生物
运动前神经元活动
门控
多巴胺能
帕金森病
医学
内科学
疾病
作者
Quanxiang Xian,Zhihai Qiu,Suresh Murugappan,Shashwati Kala,Kin Fung Wong,Danni Li,Guofeng Li,Yizhou Jiang,Yong Wu,Min Su,Xuandi Hou,Jiejun Zhu,Jinghui Guo,Weibao Qiu,Lei Sun
标识
DOI:10.1073/pnas.2220575120
摘要
Noninvasive control of neuronal activity in the deep brain can be illuminating for probing brain function and treating dysfunctions. Here, we present a sonogenetic approach for controlling distinct mouse behavior with circuit specificity and subsecond temporal resolution. Targeted neurons in subcortical regions were made to express a mutant large conductance mechanosensitive ion channel (MscL-G22S), enabling ultrasound to trigger activity in MscL-expressing neurons in the dorsal striatum and increase locomotion in freely moving mice. Ultrasound stimulation of MscL-expressing neurons in the ventral tegmental area could activate the mesolimbic pathway to trigger dopamine release in the nucleus accumbens and modulate appetitive conditioning. Moreover, sonogenetic stimulation of the subthalamic nuclei of Parkinson’s disease model mice improved their motor coordination and mobile time. Neuronal responses to ultrasound pulse trains were rapid, reversible, and repeatable. We also confirmed that the MscL-G22S mutant is more effective to sensitize neurons to ultrasound compared to the wild-type MscL. Altogether, we lay out a sonogenetic approach which can selectively manipulate targeted cells to activate defined neural pathways, affect specific behaviors, and relieve symptoms of neurodegenerative disease.
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