The temporal pattern of intracortical microstimulation pulses elicits distinct temporal and spatial recruitment of cortical neuropil and neurons.
The temporal pattern of intracortical microstimulation pulses elicits distinct temporal and spatial recruitment of cortical neuropil and neurons.
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DOI：
10.1088/1741-2552/abc29c
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发表时间：
2021-01-25
影响因子：
4
通讯作者：
Kozai TDY
中科院分区：
文献类型：
--
作者：
Eles JR;Stieger KC;Kozai TDY
治疗性神经刺激波形的刺激脉冲的间隔或分布——这里称为时间模式（TP）——已经成为调节对脑深部刺激和皮层内微刺激（ICMS）反应的重要参数。虽然长期以来人们一直认为，通过改变神经反应的编码速率来调节ICMS的TP可能是有效的，但尚不清楚它是如何在神经网络水平上改变神经反应的。本研究旨在阐明TP在网络水平上的神经反应。我们在表达钙传感器Thy1-GCaMP或谷氨酸传感器hSyn-iGluSnFr的小鼠中使用ICMS的体内双光子成像来检测II/III层神经对不同TPs刺激的反应。我们研究了在相同的平均频率（10 Hz）和相同的总电荷注入情况下，神经元钙和谷氨酸对不同爆裂程度的TPs的反应。我们还研究了一种平均频率为100 Hz，电荷注入量为10倍的控制模式。相同的平均频率（10 Hz）和相同的总电荷注入刺激训练，但不同的TPs招募不同的神经元组。超过一半的细胞（309个细胞中的60%）更喜欢其中一种。尽管它们具有不同的空间招募模式，但两种细胞表现出相似的能力，可以跟随两种TPs的30 s序列而不会失败，并且它们在刺激时表现出相似的谷氨酸释放水平。神经元钙和谷氨酸的释放均呈爆发性TP模式（在爆发性TP频率下，相对功率增加约21倍）。破裂还导致体细胞钙活性和神经pil活性之间的相关性在统计上显着升高，我们将其作为抑制性兴奋性张力的度量。有趣的是，在破裂模式中，躯体-神经细胞的相关性在统计上是TP细胞偏好的显著预测因子，这揭示了抑制-兴奋张力之间的关键联系。最后，利用中尺度成像，我们发现两种TP在刺激过程中都导致远端抑制，这揭示了TP与ICMS中抑制性兴奋性张力之间复杂的空间和时间相互作用。我们的结果可能最终表明，TP是一个有价值的参数空间，可以调节ICMS中抑制性兴奋性张力和不同的网络活动。这显示了比先前认为的速率编码更广泛的作用机制。通过暗示这些额外的机制，TP可能在临床中有更广泛的用途，应该追求扩大ICMS治疗的疗效。
The spacing or distribution of stimulation pulses of therapeutic neurostimulation waveforms—referred to here as the Temporal Pattern (TP)—has emerged as an important parameter for tuning the response to deep-brain stimulation and intracortical microstimulation (ICMS). While it has long been assumed that modulating the TP of ICMS may be effective by altering the rate coding of the neural response, it is unclear how it alters the neural response at the neural network level. The present study is designed to elucidate the neural response to TP at the network level. We use in vivo two-photon imaging of ICMS in mice expressing the calcium sensor Thy1-GCaMP or the glutamate sensor hSyn-iGluSnFr to examine the layer II/III neural response to stimulations with different TPs. We study the neuronal calcium and glutamate response to TPs with the same average frequency (10 Hz) and same total charge injection, but varying degrees of bursting. We also investigate one control pattern with an average frequency of 100 Hz and 10X the charge injection. Stimulation trains with the same average frequency (10 Hz) and same total charge injection but distinct TPs recruits distinct sets of neurons. More than half (60% of 309 cells) prefer one TP over the other. Despite their distinct spatial recruitment patterns, both cells exhibit similar ability to follow 30 s trains of both TPs without failing, and they exhibit similar levels of glutamate release during stimulation. Both neuronal calcium and glutamate release train to the bursting TP pattern (~21-fold increase in relative power at the frequency of bursting. Bursting also results in a statistically significant elevation in the correlation between somatic calcium activity and neuropil activity, which we explore as a metric for inhibitory-excitatory tone. Interestingly, soma-neuropil correlation during the bursting pattern is a statistically significant predictor of cell preference for TP, which exposes a key link between inhibitory-excitatory tone. Finally, using mesoscale imaging, we show that both TPs result in distal inhibition during stimulation, which reveals complex spatial and temporal interactions between TP and inhibitory-excitatory tone in ICMS. Our results may ultimately suggest that TP is a valuable parameter space to modulate inhibitory-excitatory tone as well as distinct network activity in ICMS. This presents a broader mechanism of action than rate coding, as previously thought. By implicating these additional mechanisms, TP may have broader utility in the clinic and should be pursued to expand the efficacy of ICMS therapies.
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影响因子：
16.6
作者：
Bitzenhofer SH;Ahlbeck J;Wolff A;Wiegert JS;Gee CE;Oertner TG;Hanganu-Opatz IL
通讯作者：
Hanganu-Opatz IL
影响因子：
17.1
作者：
Brocker DT;Swan BD;So RQ;Turner DA;Gross RE;Grill WM
通讯作者：
Grill WM
影响因子：
14
作者：
Eles, J. R.;Vazquez, A. L.;Cui, X. T.
通讯作者：
Cui, X. T.
影响因子：
5.7
作者：
Cabral, Joana;Hugues, Etienne;Deco, Gustavo
通讯作者：
Deco, Gustavo
影响因子：
16.2
作者：
Chen Q;Cichon J;Wang W;Qiu L;Lee SJ;Campbell NR;Destefino N;Goard MJ;Fu Z;Yasuda R;Looger LL;Arenkiel BR;Gan WB;Feng G
通讯作者：
Feng G