A tool for monitoring cell type-specific focused ultrasound neuromodulation and control of chronic epilepsy.
A tool for monitoring cell type-specific focused ultrasound neuromodulation and control of chronic epilepsy.
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DOI：
10.1073/pnas.2206828119
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发表时间：
2022-11-16
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
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作者：
超声可以通过头骨聚焦到深度大脑上，尽管它的效用很广，但对特定细胞类型的焦点的作用几乎完全未知。自由行为的动物中的细胞类型。
聚焦超声（FUS）是对深度大脑活动的非侵入性调节的强大工具，这些潜在的耐火性癫痫病的工具； a fiber Photometry Coupled focused Ultrasound System (PhoCUS) for simply monitoring FUS effects on neuronal activity of subcortical genetically targeted cell types in free behaving animals. We identified a parameter set that selectively increases activity of parvalbumin interneurons while suppressing excitatory neurons in the hippocampus. A net inhibitory effect localized to the hippocampus was further confirmed through whole brain metabolic imaging.最后，这些抑制性选择性参数在慢性临时叶癫痫的海藻酸盐模型中实现了明显的尖峰抑制，为将来的无创疗法打开了大门。
Ultrasound can be focused through skull onto the deep brain, altering neural activity noninvasively. Despite its broad utility, the action of focused ultrasound on specific cell types is almost entirely unknown. Understanding cell type–specific responses to FUS would allow selection of ultrasound waveforms that engage the intended targets while limiting effects on off-target fields. We developed a system combining FUS targeting and optical recording of virally labeled deep brain cell types in freely behaving animals. We used the tool to identify a protocol for the hippocampus that selectively increases inhibitory neural activity while decreasing excitatory activity with high spatial specificity. The protocol robustly suppressed epileptiforms in a chronic epilepsy model demonstrating the tool’s potential for examining experimental FUS therapies. Focused ultrasound (FUS) is a powerful tool for noninvasive modulation of deep brain activity with promising therapeutic potential for refractory epilepsy; however, tools for examining FUS effects on specific cell types within the deep brain do not yet exist. Consequently, how cell types within heterogeneous networks can be modulated and whether parameters can be identified to bias these networks in the context of complex behaviors remains unknown. To address this, we developed a fiber Photometry Coupled focused Ultrasound System (PhoCUS) for simultaneously monitoring FUS effects on neural activity of subcortical genetically targeted cell types in freely behaving animals. We identified a parameter set that selectively increases activity of parvalbumin interneurons while suppressing excitatory neurons in the hippocampus. A net inhibitory effect localized to the hippocampus was further confirmed through whole brain metabolic imaging. Finally, these inhibitory selective parameters achieved significant spike suppression in the kainate model of chronic temporal lobe epilepsy, opening the door for future noninvasive therapies.
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DOI：
10.1073/pnas.2006980118
发表时间：
2021-02-09
影响因子：
11.1
作者：
Sorum B;Rietmeijer RA;Gopakumar K;Adesnik H;Brohawn SG
通讯作者：
Brohawn SG
影响因子：
3.7
作者：
Prieto ML;Ömer O;Khuri-Yakub BT;Maduke MC
通讯作者：
Maduke MC
影响因子：
3.3
作者：
Collins, CM;Smith, MB;Turner, R
通讯作者：
Turner, R
影响因子：
16.6
作者：
通讯作者：
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影响因子：
9.2
作者：
Deffieux, Thomas;Younan, Youliana;Aubry, Jean-Francois
通讯作者：
Aubry, Jean-Francois