Differential effects of long and short train theta burst stimulation on LTP induction in rat anterior cingulate cortex slices:Multi-electrode array recordings

长串与短串θ节律刺激在大鼠前扣带回皮质脑片诱导长时程增强效应的不同作用:平面微电极阵列记录技术(英文)

Objective There is substantial evidence supporting the notion that the anterior cingulate cortex （ACC） is an important limbic structure involved in multiple brain functions such as sensory perception, motor conflict monitoring, memory, emotion and cognition. It has been shown that long term potentiation （LTP） is an important synaptic model of neural plasticity in the ACC, however, little is known about the spatiotemporal properties of ACC at network level. The present study was designed to see the LTP induction effects across different layers of the ACC by using different conditioning stimuli （CS） protocols. Methods A unique multi-electrode array recording technique was used in the acutely-dissociated ACC slices of rats. Long and short train theta burst stimulation （TBS） paradigms were applied in layer V-VI as the CS and the LTP induction effects were compared across different layers of the ACC. Briefly, both long and short train TBS are composed of bursts （4 pulses at 100 Hz） with a 200 ms interval, however, the former （TBS1） was with 10 trains and the latter （TBS2） was with 5 trains. After test stimulation at layer V-VI in the ACC, network field potentials （FPs） could be simultaneously recorded across all layers of the ACC. Results The waveforms of FPs were different across different layers. Namely, positive-going waveforms were recorded in layer I and negative-going waveforms were recorded in layers V-VI, in contrast, complex waveforms were localized mainly in layers II-III. Following application of two CS protocols, the induction rate of LTP was significantly different between TBS 1 and TBS2 regardless of the spatial properties. TBS1 had more than 60% success, while TBS2 was less than 25% in induction of LTP. Moreover, both the 2 CS protocols could induce LTP in layers II-III and layers V-VI without layer-related difference. However, no LTP was inducible in layer I. Conclusion The present findings indicate that stimulation protocols may, at least in part, account for a large portion of variations among previous LTP studies, and hence highlight the importance of selecting the best LTP induction protocol when designing such experiments. Moreover, the present results demonstrate the prominent superiority of multi-electrode array recording in revealing the network properties of synaptic activities in the ACC, especially in comparing the spatiotemporal characteristics between different layers of this structure.

目的大量研究显示前扣带回(anterior cingulate cortex,ACC)是一个多功能的边缘系统结构,参与诸如知觉,运动,情绪和认知等多种高级脑功能。有证据显示长时程增强现象(long-term potentiation,LTP)是研究ACC内发生神经元突触可塑性变化的重要模型。然而,迄今为止,关于ACC神经网络的时空特性仍少为人知。本研究旨在应用平面微电极阵列记录技术观察不同长度θ节律串刺激对诱发大鼠ACC区域不同层结构的LTP的影响。方法采用平面微电极阵列记录技术,在急性分离的大鼠ACC脑片上进行记录。通过实验电刺激V-VI层,记录ACC各层场电位。然后应用两种θ节律串刺激(theta burst stimulation,TBS)作为条件刺激诱发ACC脑区LTP,并比较不同层的LTP诱出效果。两种刺激模式参数为:TBS1,100Hz,4个双向方波脉冲为一串,重复10次,间隔200ms;TBS2,100Hz,4个双向方波脉冲为一串,重复5次,间隔200ms。实验刺激前扣带回深层可以分别在I层,Ⅱ-Ⅲ层及V-VI层同时诱出三种波形不同的场电位:I层为正向波,V-VI层为负向波,Ⅱ-Ⅲ层以复杂的波形为主。结果在实验刺激位点给予两种不同的条件刺激后,长串TBS1条件刺激的LTP诱出率显著地高于短串TBS2条件刺激,即TBS1的LTP诱出率超过60%,而TBS2的LTP诱出率少于25%。此外,层间分析结果显示LTP主要发生在Ⅱ-Ⅲ层及V-VI层,I层不能诱出LTP。进一步分析表明,无论是LTP诱出率还是幅度在Ⅱ-Ⅲ层及V-VI层之间均无显著差别。结论本实验结果提示同一刺激模式但重复刺激时间长短不同也可能导致LTP诱出率不同,这可能是为什么以往报导关于前扣带回LTP诱出率结果不同的一个关键原因之一,因此在设计此类实验时选择最佳刺激参数更为重要。另外,本实验证明平面微电极阵列记录技术在研究前扣带回皮质突触可塑性的网络特征,尤其是比较不同层结构中的时空特性具有单电极无法比拟的优势。