Department of Biomedical Engineering, The City College of New York, New York, NY, USA.
Department of Biomedical Engineering, The City College of New York, New York, NY, USA.
Brain Stimul. 2021 May-Jun;14(3):588-597. doi: 10.1016/j.brs.2021.03.001. Epub 2021 Mar 22.
Transcranial direct current stimulation (DCS) has lasting effects that may be explained by a boost in synaptic long-term potentiation (LTP). We hypothesized that this boost is the result of a modulation of somatic spiking in the postsynaptic neuron, as opposed to indirect network effects. To test this directly we record somatic spiking in a postsynaptic neuron during LTP induction with concurrent DCS.
We performed rodent in-vitro patch-clamp recordings at the soma of individual CA1 pyramidal neurons. LTP was induced with theta-burst stimulation (TBS) applied concurrently with DCS. To test the causal role of somatic polarization, we manipulated polarization via current injections. We also used a computational multi-compartment neuron model that captures the effect of electric fields on membrane polarization and activity-dependent synaptic plasticity.
TBS-induced LTP was enhanced when paired with anodal DCS as well as depolarizing current injections. In both cases, somatic spiking during the TBS was increased, suggesting that evoked somatic activity is the primary factor affecting LTP modulation. However, the boost of LTP with DCS was less than expected given the increase in spiking activity alone. In some cells, we also observed DCS-induced spiking, suggesting DCS also modulates LTP via induced network activity. The computational model reproduces these results and suggests that they are driven by both direct changes in postsynaptic spiking and indirect changes due to network activity.
DCS enhances synaptic plasticity by increasing postsynaptic somatic spiking, but we also find that an increase in network activity may boost but also limit this enhancement.
经颅直流电刺激(DCS)具有持久的效果,这可以通过突触长时程增强(LTP)的增强来解释。我们假设这种增强是由于突触后神经元中体细胞尖峰的调制,而不是间接的网络效应。为了直接测试这一点,我们在 LTP 诱导过程中同时进行 DCS 时记录突触后神经元中的体细胞尖峰。
我们在单个 CA1 锥体神经元的体部进行了啮齿动物在体膜片钳记录。使用 theta 爆发刺激(TBS)与 DCS 同时诱导 LTP。为了测试体细胞极化的因果作用,我们通过电流注入来操纵极化。我们还使用了一个计算多室神经元模型,该模型捕获了电场对膜极化和活动依赖性突触可塑性的影响。
当与阳极 DCS 以及去极化电流注入配对时,TBS 诱导的 LTP 得到增强。在这两种情况下,TBS 期间的体细胞尖峰都增加了,这表明诱发的体细胞活动是影响 LTP 调制的主要因素。然而,DCS 增强的 LTP 小于仅增加尖峰活动所预期的程度。在一些细胞中,我们还观察到 DCS 诱导的尖峰,这表明 DCS 还通过诱导的网络活动来调节 LTP。计算模型再现了这些结果,并表明它们是由突触后尖峰的直接变化和网络活动引起的间接变化驱动的。
DCS 通过增加突触后体细胞尖峰来增强突触可塑性,但我们也发现网络活动的增加可以增强但也限制这种增强。