Thimm Andreas, Funke Klaus
Department of Neurophysiology, Medical Faculty, Ruhr-University Bochum, 44780, Bochum, Germany.
J Physiol. 2015 Feb 15;593(4):967-85. doi: 10.1113/jphysiol.2014.282467. Epub 2015 Jan 12.
Theta-burst stimulation (TBS) applied via transcranial magnetic stimulation is able to modulate human cortical excitability. Here we investigated in a rat model how two different forms of TBS, intermittent (iTBS) and continuous (cTBS), affect sensory responses in rat barrel cortex. We found that iTBS but less cTBS promoted late (>18 ms) sensory response components while not affecting the earliest response (8-18 ms). The effect increased with each of the five iTBS blocks applied. cTBS somewhat reduced the early response component after the first block but had a similar effect as iTBS after four to five blocks. We conclude that iTBS primarly modulates the activity of (inhibitory) cortical interneurons while cTBS may first reduce general neuronal excitability with a single block but reverse to iTBS-like effects with application of several blocks.
Cortical sensory processing varies with cortical state and the balance of inhibition to excitation. Repetitive transcranial magnetic stimulation (rTMS) has been shown to modulate human cortical excitability. In a rat model, we recently showed that intermittent theta-burst stimulation (iTBS) applied to the corpus callosum, to activate primarily supragranular cortical pyramidal cells but fewer subcortical neurons, strongly reduced the cortical expression of parvalbumin (PV), indicating reduced activity of fast-spiking interneurons. Here, we used the well-studied rodent barrel cortex system to test how iTBS and continuous TBS (cTBS) modulate sensory responses evoked by either single or double stimuli applied to the principal (PW) and/or adjacent whisker (AW) in urethane-anaesthetized rats. Compared to sham stimulation, iTBS but not cTBS particularly enhanced late (>18 ms) response components of multi-unit spiking and local field potential responses in layer 4 but not the very early response (<18 ms). Similarly, only iTBS diminished the suppression of the second response evoked by paired PW or AW-PW stimulation at 20 ms intervals. The effects increased with each of the five iTBS blocks applied. With cTBS a mild effect similar to that of iTBS was first evident after 4-5 stimulation blocks. Enhanced cortical c-Fos and zif268 expression but reduced PV and GAD67 expression was found only after iTBS, indicating increased cortical activity due to lowered inhibition. We conclude that iTBS but less cTBS may primarily weaken a late recurrent-type cortical inhibition mediated via a subset of PV+ interneurons, enabling stronger late response components believed to contribute to the perception of sensory events.
经颅磁刺激施加的theta爆发刺激（TBS）能够调节人类皮层兴奋性。在此，我们在大鼠模型中研究了两种不同形式的TBS，即间歇性（iTBS）和连续性（cTBS），如何影响大鼠桶状皮层的感觉反应。我们发现iTBS而非cTBS促进了晚期（>18毫秒）感觉反应成分，同时不影响最早的反应（8 - 18毫秒）。随着施加的五个iTBS组块中的每一个，这种效应增强。cTBS在第一个组块后稍微降低了早期反应成分，但在四到五个组块后具有与iTBS相似的效应。我们得出结论，iTBS主要调节（抑制性）皮层中间神经元的活动，而cTBS可能在单个组块时首先降低总体神经元兴奋性，但在施加几个组块后转变为类似iTBS的效应。
皮层感觉处理随皮层状态以及抑制与兴奋的平衡而变化。重复经颅磁刺激（rTMS）已被证明可调节人类皮层兴奋性。在大鼠模型中，我们最近表明，应用于胼胝体的间歇性theta爆发刺激（iTBS），主要激活颗粒上层皮层锥体细胞但较少激活皮层下神经元，强烈降低了小白蛋白（PV）的皮层表达，表明快速发放中间神经元的活动减少。在此，我们使用经过充分研究的啮齿动物桶状皮层系统，来测试iTBS和连续性TBS（cTBS）如何调节在乌拉坦麻醉的大鼠中，施加于主要（PW）和/或相邻触须（AW）的单个或双刺激所诱发的感觉反应。与假刺激相比，iTBS而非cTBS特别增强了第4层多单位放电和局部场电位反应的晚期（>18毫秒）反应成分，但不增强非常早期的反应（<18毫秒）。同样，只有iTBS减少了以20毫秒间隔施加的成对PW或AW - PW刺激所诱发的第二个反应的抑制。随着施加的五个iTBS组块中的每一个，这种效应增强。对于cTBS，在4 - 5个刺激组块后首次明显出现与iTBS相似的轻微效应。仅在iTBS后发现皮层c - Fos和zif268表达增强但PV和GAD67表达降低，表明由于抑制降低导致皮层活动增加。我们得出结论，iTBS而非cTBS可能主要削弱经由一部分PV + 中间神经元介导的晚期反馈型皮层抑制，从而使被认为有助于感觉事件感知的更强晚期反应成分得以出现。
