Intrinsic functional neuron-type selectivity of transcranial focused ultrasound neuromodulation.

Intrinsic functional neuron-type selectivity of transcranial focused ultrasound neuromodulation.
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DOI:
10.1038/s41467-021-22743-7
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发表时间:
2021-05-04
影响因子:
16.6
通讯作者:
He B
He B
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Yu K;Niu X;Krook-Magnuson E;He B

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经颅聚焦超声(tFUS)是一种很有前途的神经调节技术,但其机制尚不清楚。我们假设,如果tFUS参数在不同的神经元群体中表现出不同的调制效应,那么可以通过识别这些神经元群体中的独特特征来理解该机制。在这项工作中,我们研究了tFUS刺激对不同功能的神经元类型在体内麻醉啮齿动物的大脑。根据通过颅内电生理记录获得的细胞外锋电位形状,将单个神经元记录分为规则锋电位和快速锋电位单位,并在光兴奋性和抑制性神经元的转基因光遗传学小鼠模型中进一步验证。我们发现,兴奋性和抑制性神经元在响应超声脉冲重复频率(PRF)的本质上是不同的。结果表明,我们可以优先通过调整tFUS PRF非侵入性地靶向特定的神经元类型。进一步测试了化学诱变的大鼠和遗传诱变的小鼠,以验证tFUS诱导的直接局部神经效应,而没有潜在的听觉混淆。低强度经颅聚焦超声(tFUS)是一种具有高度空间特异性的非侵入性神经调节技术。作者表明,兴奋性和抑制性神经元对tFUS的反应不同,这表明通过非侵入性tFUS优先靶向特定神经元类型的可能性。
Transcranial focused ultrasound (tFUS) is a promising neuromodulation technique, but its mechanisms remain unclear. We hypothesize that if tFUS parameters exhibit distinct modulation effects in different neuron populations, then the mechanism can be understood through identifying unique features in these neuron populations. In this work, we investigate the effect of tFUS stimulation on different functional neuron types in in vivo anesthetized rodent brains. Single neuron recordings were separated into regular-spiking and fast-spiking units based on their extracellular spike shapes acquired through intracranial electrophysiological recordings, and further validated in transgenic optogenetic mice models of light-excitable excitatory and inhibitory neurons. We show that excitatory and inhibitory neurons are intrinsically different in response to ultrasound pulse repetition frequency (PRF). The results suggest that we can preferentially target specific neuron types noninvasively by tuning the tFUS PRF. Chemically deafened rats and genetically deafened mice were further tested for validating the directly local neural effects induced by tFUS without potential auditory confounds. Low-intensity transcranial focused ultrasound (tFUS) is a non-invasive neuromodulation technique with high spatial specificity. The authors show that excitatory and inhibitory neurons respond differently to tFUS, suggesting the possibility of preferentially targeting specific neuron types via noninvasive tFUS.