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单脉冲聚焦超声刺激因果电生理活动的时空特征:在海马脑片上的研究。

Spatio-temporal characterization of causal electrophysiological activity stimulated by single pulse focused ultrasound: anstudy on hippocampal brain slices.

机构信息

LabTAU, INSERM, Centre Léon Bérard, Université Lyon 1, Univ Lyon, F-69003 Lyon, France.

Neuroglial Interactions in Cerebral Physiopathology, Center for Interdisciplinary Research in Biology, Collège de France, CNR UMR 7241, INSERM U1050, Paris, France.

出版信息

J Neural Eng. 2021 Mar 2;18(2). doi: 10.1088/1741-2552/abdfb1.

DOI:10.1088/1741-2552/abdfb1
PMID:33494078
Abstract

The brain operates via generation, transmission and integration of neuronal signals and most neurological disorders are related to perturbation of these processes. Neurostimulation by focused ultrasound (FUS) is a promising technology with potential to rival other clinically used techniques for the investigation of brain function and treatment of numerous neurological diseases. The purpose of this study was to characterize spatial and temporal aspects of causal electrophysiological signals directly stimulated by short, single pulses of FUS onmouse hippocampal brain slices.Microelectrode arrays (MEAs) are used to study the spatio-temporal dynamics of extracellular neuronal activities both at the single neuron and neural networks scales. Hence, MEAs provide an excellent platform for characterization of electrical activity generated, modulated and transmitted in response to FUS exposure. In this study, a novel mixed FUS/MEA platform was designed for the spatio-temporal description of the causal responses generated by single 1.78 MHz FUS pulses inmouse hippocampal brain slices.Our results show that FUS pulses can generate local field potentials (LFPs), sustained by synchronized neuronal post-synaptic potentials, and reproducing network activities. LFPs induced by FUS stimulation were found to be repeatable to consecutive FUS pulses though exhibiting a wide range of amplitudes (50-600V), durations (20-200 ms), and response delays (10-60 ms). Moreover, LFPs were spread across the hippocampal slice following single FUS pulses thus demonstrating that FUS may be capable of stimulating different neural structures within the hippocampus.Current knowledge on neurostimulation by ultrasound describes neuronal activity generated by trains of repetitive ultrasound pulses. This novel study details the causal neural responses produced by single-pulse FUS neurostimulation while illustrating the distribution and propagation properties of this neural activity along major neural pathways of the hippocampus.

摘要

大脑通过神经元信号的产生、传递和整合来运作,大多数神经疾病都与这些过程的紊乱有关。聚焦超声(FUS)神经刺激是一种很有前途的技术,有可能与其他临床应用技术相媲美,用于研究大脑功能和治疗多种神经疾病。本研究的目的是描述通过短的、单次 FUS 脉冲直接刺激小鼠海马脑片时因果电生理信号的空间和时间方面。微电极阵列(MEA)用于研究单个神经元和神经网络尺度上的细胞外神经元活动的时空动态。因此,MEA 为描述对 FUS 暴露的电活动的产生、调制和传输提供了一个极好的平台。在这项研究中,设计了一种新型的混合 FUS/MEA 平台,用于对单个 1.78MHz FUS 脉冲在小鼠海马脑片中产生的因果反应进行时空描述。我们的结果表明,FUS 脉冲可以产生局部场电位(LFPs),由同步的神经元突触后电位维持,并再现网络活动。发现 FUS 刺激产生的 LFPs 可以对连续的 FUS 脉冲重复,但表现出广泛的幅度(50-600V)、持续时间(20-200ms)和响应延迟(10-60ms)。此外,LFPs 在单个 FUS 脉冲后在海马切片中传播,表明 FUS 可能能够刺激海马内的不同神经结构。目前关于超声神经刺激的知识描述了由重复超声脉冲产生的神经元活动。这项新的研究详细描述了由单脉冲 FUS 神经刺激产生的因果神经反应,同时说明了这种神经活动沿海马体主要神经通路的分布和传播特性。

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