Mechanisms underlying integration of synaptic plasticity in neuronal networks

突触连接的活动依赖性修饰可能在发育和学习记忆过程中的适当网络形成中起关键作用。基于多部位刺激的能力，MEA记录被应用于观察由重复施加时间相关刺激引起的诱发反应的修改。皮层神经元自发活动呈现发育性变化，在体外培养约一个月后达到稳定状态。诱发反应也取决于他们的发展阶段。因此，在这项工作中，超过40天的体外成熟培养物用于记录。一系列记录包括（1）对测试刺激的诱发反应和（2）对相关刺激的反应。测试刺激由100次来自A部位的单脉冲刺激和100次来自B部位的单脉冲刺激组成。每6秒施加一次单部位刺激。相关刺激由100次双脉冲组成。从部位A施加的第一个脉冲之后是从部位B施加的第二个脉冲，具有固定的时间延迟。测试了100、50、20、10和0 ms的时间延迟。整个实验过程由6组测试刺激和5组相关刺激组成：test1-A&B100-test 2-A&B50-test 3-A&B20-test 4-A&B10-tests-A& B 0-test 6。诱发活动由早、晚成分组成。在初始状态下，几乎没有记录到晚期成分。在相关刺激之后，出现了较强的迟发成分。晚期成分分别在30 ms和20 ms后检测到。为了分析诱发活动变化与所施加的相关刺激之间的关系，计算了互相关函数。这些结果表明，所施加的相关刺激的性质可能反映在诱发反应的时空结构中。

Activity-dependent modification of synaptic connections probably plays a key role in both proper network formation during development and learning and memory. Based on the capability of multi-site stimulation, MEA recording was applied to see modification of evoked responses induced by repetitive application of temporally correlated stimuli. Cortical neurons show developmental changes in spontaneous activity and reach the steady state after about one month in vitro. Evoked responses also depend on their developmental stages. Thus, in this work, matured cultures of more than 40 days in vitro were used for recording. A series of recording consists of (1) evoked responses to test stimuli and (2) responses to the correlated stimuli. The test stimuli were composed of 100 times of single pulse stimulus from site A and another 100 times from site B. Each single-site stimulation was applied every six seconds. The correlated stimuli consisted of 100 times of double pulses. The first pulse applied from site A was followed by the second pulse from the site B with a fixed time delay. Time delays of 100, 50, 20, 10, and 0 ms were tested. The total process of the experiment was composed of 6 sets of test stimuli and 5 sets of correlated stimuli: test1-A＆B100-test2-A＆B50-test3-A＆B20-test4-A＆B10-tests-A＆B0-test6. The evoked activity consisted of early and late components. At the initial state, almost no late components were recorded. After the correlated stimuli, strong late components appeared. The late components were detected after about 30 ms, and 20 ms, respectively. To analyze relationship between induced activity-changes and the applied correlated stimuli, cross-correlation functions were calculated. These results suggested that the properties of the applied correlated stimuli might be reflected in the spatio-temporal structures in the evoked responses.