Department of Biomedical Engineering, The City College of New York, CUNY, 160 Convent Avenue, New York, NY, USA.
Brain Stimul. 2022 Jan-Feb;15(1):57-62. doi: 10.1016/j.brs.2021.10.552. Epub 2021 Nov 5.
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.
已知直流刺激（DCS）产生的电场可调节体外活性依赖突触可塑性。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种机制解释。然而，尽管在体外突触可塑性实验中使用了比人类常规 tDCS 预期更强的场强（20 V/m 对 1 V/m），但实验结果显示效果相对较小。因此，需要提高 tDCS 在实际场强下的有效性。在这里，我们利用学习效应已知会随着多次学习（称为间隔学习）而积累的观察结果。
我们提出，在间隔学习范式中，DCS 对突触长时程增强（LTP）的影响会随时间累积，从而揭示出更接近实际场强的效果。
我们利用重复的θ爆发刺激（TBS）诱导 LTP 的标准间隔学习模型，在海马切片中进行实验。我们研究了 DCS 在海马 CA1 区 LTP 诱导过程中，与各种强度的 TBS 配对时的累积效应。
正如预期的那样，在重复的 TBS 爆发刺激期间施加 DCS 会导致 LTP 增加。这种间隔学习效应随着强 TBS 方案和更强的场迅速饱和。相比之下，较弱的 TBS 和最弱的 2.5 V/m 电场产生了最强的相对效率（每施加 1 V/m 可增强 LTP 12%）。
较弱的 DCS 会导致间隔学习对突触可塑性产生相对较强的累积效应。之前的体外研究中可能存在饱和效应，掩盖了更强的效应大小。DCS 的相对效应大小现在更接近人类 tDCS 实验的结果。
