Weak DCS causes a relatively strong cumulative boost of synaptic plasticity with spaced learning.
Weak DCS causes a relatively strong cumulative boost of synaptic plasticity with spaced learning.
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DOI：
10.1016/j.brs.2021.10.552
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发表时间：
2022-01
影响因子：
7.7
通讯作者：
Parra LC
中科院分区：
文献类型：
--
作者：
Sharma M;Farahani F;Bikson M;Parra LC
在体外，直流电刺激(DC)产生的电场可以调节活性依赖的突触可塑性。这为经颅直流电刺激(Tdcs)在人类学习实验中观察到的持久行为效应提供了一个机制解释。然而，之前的体外突触可塑性实验显示，尽管使用了强场，但与人类传统的tDC相比(20V/m比1V/m)，影响相对较小。因此，有必要提高TDC在实际场强下的有效性。在这里，我们利用了这样一个观察，即学习的效果已知会在多次学习中积累，即所谓的间隔学习。我们认为，在空间学习范式中，DCs对突触长时程增强(LTP)的影响随着时间的推移而积累，从而在更现实的场强下揭示出影响。我们利用间隔学习的标准模型，通过在海马片准备中反复发作theta Burst刺激(TBS)来诱导LTP。我们研究了在诱导大鼠海马脑片CA1区LTP的过程中，不同强度的DCs与TBS联合应用的累积效应。正如所预测的那样，在反复进行theta Burst刺激(TBS)时，使用DCs会导致LTP增加。这种间隔的学习效果很快就被强大的TBS协议和更强大的领域饱和。相反，较弱的TBS和2.5V/m的最弱电场导致了最强的相对效率(每施加1V/m，LTP增加12%)。弱的dcs导致较强的空间学习对突触可塑性的累积效应。在之前的体外研究中，他汀类药物可能掩盖了更强的效应大小。集散控制系统的相对效应大小现在更接近于人类的tDCS实验。
Electric fields generated during direct current stimulation (DCS) are known to modulate activity-dependent synaptic plasticity in-vitro. This provides a mechanistic explanation for the lasting behavioral effects observed with transcranial direct current stimulation (tDCS) in human learning experiments. However, previous in-vitro synaptic plasticity experiments show relatively small effects despite using strong fields compared to what is expected with conventional tDCS in humans (20 V/m vs. 1 V/m). There is therefore a need to improve the effectiveness of tDCS at realistic field intensities. Here we leverage the observation that effects of learning are known to accumulate over multiple bouts of learning, known as spaced learning. We propose that effects of DCS on synaptic long-term potentiation (LTP) accumulate over time in a spaced learning paradigm, thus revealing effects at more realistic field intensities. We leverage a standard model for spaced learning by inducing LTP with repeated bouts of theta burst stimulation (TBS) in hippocampal slice preparations. We studied the cumulative effects of DCS paired with TBS at various intensities applied during the induction of LTP in the CA1 region of rat hippocampal slices. As predicted, DCS applied during repeated bouts of theta burst stimulation (TBS) resulted in an increase of LTP. This spaced learning effect is saturated quickly with strong TBS protocols and stronger fields. In contrast, weaker TBS and the weakest electric fields of 2.5 V/m resulted in the strongest relative efficacies (12% boost in LTP per 1 V/m applied). Weak DCS causes a relatively strong cumulative effect of spaced learning on synaptic plasticity. Staturarion may have masked stronger effects sizes in previous in-vitro studies. Relative effect sizes of DCS are now closer in line with human tDCS experiments.
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