Department of Biomedical Engineering, Boston University, Boston, MA, United States of America.
Department of Pharmacology and Experimental Therapeutics, Boston University, Boston, MA, United States of America.
J Neural Eng. 2024 Sep 9;21(5):056008. doi: 10.1088/1741-2552/ad731c.
. Transcranial ultrasound (US) stimulation serves as an external input to a neuron, and thus the evoked response relies on neurons' intrinsic properties. Neural activity is limited to a couple hundred hertz and often exhibits preference to input frequencies. Accordingly, US pulsed at specific physiologic pulse repetition frequencies (PRFs) may selectively engage neurons with the corresponding input frequency preference. However, most US parametric studies examine the effects of supraphysiologic PRFs. It remains unclear whether pulsing US at different physiologic PRFs could activate distinct neurons in the awake mammalian brain.. We recorded cellular calcium responses of individual motor cortex neurons to US pulsed at PRFs of 10, 40, and 140 Hz in awake mice. We compared the evoked responses across these PRFs in the same neurons. To further understand the cell-type dependent effects, we categorized the recorded neurons as parvalbumin positive fast spiking interneurons or putative excitatory neurons and analyzed single-cell mechanosensitive channel expression in mice and humans using the Allen Brain Institute's RNA-sequencing databases.. We discovered that many neurons were preferentially activated by only one PRF and different PRFs selectively engaged distinct neuronal populations. US-evoked cellular calcium responses exhibited the same characteristics as those naturally occurring during spiking, suggesting that US increases intrinsic neuronal activity. Furthermore, evoked responses were similar between fast-spiking inhibitory neurons and putative excitatory neurons. Thus, variation in individual neuron's cellular properties dominates US-evoked response heterogeneity, consistent with our observed cell-type independent expression patterns of mechanosensitive channels across individual neurons in mice and humans. Finally, US transiently increased network synchrony without producing prolonged over-synchronization that could be detrimental to neural circuit functions.. These results highlight the feasibility of activating distinct neuronal subgroups by varying PRF and the potential to improve neuromodulation effects by combining physiologic PRFs.
经颅超声(US)刺激可作为神经元的外部输入,因此诱发反应依赖于神经元的固有特性。神经活动的频率限制在几百赫兹,并且经常表现出对输入频率的偏好。因此,以特定生理脉冲重复频率(PRF)脉冲的 US 可能会选择性地使具有相应输入频率偏好的神经元参与。然而,大多数 US 参数研究都检查了超生理 PRF 的影响。目前尚不清楚以不同生理 PRF 脉冲 US 是否可以激活清醒哺乳动物大脑中的不同神经元。
我们在清醒小鼠中记录了单个运动皮层神经元对 PRF 为 10、40 和 140 Hz 的 US 脉冲的细胞钙反应。我们比较了同一神经元在这些 PRF 下的诱发反应。为了进一步了解细胞类型依赖性的影响,我们将记录的神经元分为囊泡相关蛋白阳性快速放电中间神经元或假定兴奋性神经元,并使用艾伦脑研究所的 RNA-seq 数据库分析了小鼠和人类中的单细胞机械敏感通道表达。
我们发现,许多神经元仅被一个 PRF 优先激活,而不同的 PRF 则选择性地激活了不同的神经元群体。US 诱发的细胞钙反应表现出与自然放电期间相似的特征,表明 US 增加了内在神经元的活性。此外,快速放电抑制神经元和假定兴奋性神经元之间的诱发反应相似。因此,个体神经元的细胞特性变化主导着 US 诱发反应的异质性,与我们在小鼠和人类中观察到的单个神经元中机械敏感通道的细胞类型独立表达模式一致。最后,US 短暂增加了网络同步性,而不会产生可能对神经回路功能有害的长时间过度同步。
这些结果突出了通过改变 PRF 来激活不同神经元亚群的可行性,以及通过结合生理 PRF 来改善神经调节效果的潜力。