Effects of direct current stimulation on synaptic plasticity in a single neuron.

Effects of direct current stimulation on synaptic plasticity in a single neuron.
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DOI:
10.1016/j.brs.2021.03.001
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发表时间:
2021-05
期刊:
影响因子:
7.7
通讯作者:
Parra LC
Parra LC
中科院分区:
医学1区
文献类型:
--
作者:
Farahani F;Kronberg G;FallahRad M;Oviedo HV;Parra LC

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经颅直流电刺激(DC)具有持久的效应,这可能是由于突触长时程增强(LTP)的增加。我们假设,这种增强是突触后神经元体细胞尖峰信号调制的结果,而不是间接的网络效应。为了直接测试这一点,我们记录了在LTP与并发的DC诱导过程中突触后神经元的体细胞尖峰。我们在单个CA1锥体神经元的胞体进行了啮齿动物体外膜片钳记录。电刺激(TBS)与DCs同时应用诱导LTP。为了测试躯体极化的因果作用,我们通过电流注入来操纵极化。我们还使用了一个计算的多室神经元模型,该模型捕捉了电场对膜极化和活性依赖的突触可塑性的影响。TBS诱导的LTP在与阳极DC和去极化电流注射配对时得到增强。在这两种情况下,TBS期间的体细胞尖峰增加,这表明诱发的体细胞活动是影响LTP调制的主要因素。然而,仅考虑到尖峰活动的增加,使用DCS对LTP的促进作用低于预期。在一些细胞中,我们还观察到了DCs诱导的尖峰信号,这表明DCs也通过诱导网络活动来调节LTP。计算模型再现了这些结果,并表明它们是由突触后放电的直接变化和网络活动引起的间接变化驱动的,但我们也发现,网络活动的增加可能会促进但也会限制这种增强。
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.
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