Paradoxical enhancement of long-term potentiation in poor-learning rats at low test stimulus intensities
Paradoxical enhancement of long-term potentiation in poor-learning rats at low test stimulus intensities
复制标题
低测试刺激强度下学习不良大鼠的长时程增强的反常增强
作者：
K. Jeffery
许多经验证据和大量理论模型都表明突触功效的改变是记忆形成的机制。为了评估理论模型，有必要获得与学习与实验诱导的突触功效变化（例如长时程增强，LTP）相关的定量实验数据。此类实验中的一个重要问题是如何量化给定刺激方案诱导的 LTP。相关的是非正式众所周知的观察结果，即 LTP 幅度似乎随着用于引起基线反应的刺激强度而变化。本研究发现，使用 LTP 测量来规避这种变化，学习与增强之间出现了很强的负相关关系。将空间学习能力与随后的 LTP 诱导强度进行比较，如下：大鼠在水迷宫中接受一天的空间训练，然后进行 5 天的双侧穿通路径强直刺激。在破伤风前后的一系列刺激强度（输入/输出[IO]曲线）上诱发基线电生理反应。尽管在整个 IO 曲线上都观察到了 LTP，但它随着电流的增加而平滑下降。然后根据动物的水迷宫表现和比较好学习者和差学习者的 IO 曲线对动物进行分组。强直刺激后，学习和诱发电位大小与弱测试刺激之间存在动物内负相关，与强刺激之间存在正相关。良好和较差的空间学习者在 IO 曲线上的 LTP 下降情况不同；较差的学习者在接近零强度的测试刺激下表现出更高的增强百分比，但整个曲线上的 LTP 下降得更快。因此，研究结果是：（1）测得的 LTP 量随着刺激强度的增加而系统性下降，（2）下降的参数与空间学习能力相关。这些结果提出了两个重要问题。首先，由于测得的 LTP 在 IO 曲线上系统性地变化，因此对于定量分析来说，使用单一测试刺激强度的广泛使用的 LTP 测量方法似乎有丢失数据重要特征的风险。建议采用一种包含一系列刺激强度数据的测量方法。其次，当使用这样的衡量标准时，空间学习能力与 LTP 存在显着的负相关关系。对这些看似矛盾的结果进行了讨论。
Much empirical evidence and numerous theoretical models point to modification of synaptic efficacy as a mechanism for memory formation. To evaluate theoretical models, it is necessary to obtain quantitative experimental data relating learning to experimentally induced synaptic efficacy changes (such as long-term potentiation, LTP). An important problem in this type of experiment is how to quantify the LTP induced by a given stimulation protocol. Of relevance is the informally well-known observation that LTP magnitude appears to vary as a function of the intensity of the stimulus used to evoke baseline responses. The present study found that using a measure of LTP that circumvents this variation, a strong negative correlation of learning with potentiation emerges. Spatial learning ability was compared with the magnitude of subsequent LTP induction as follows: rats underwent a day of spatial training in a watermaze followed by 5 days of bilateral perforant path tetanisation. Baseline electrophysiological responses were evoked over a range of stimulus intensities (input/output [IO] curves) before and after tetanisation. Although LTP was observed across the whole of the IO curve, it showed a smooth decline with increasing current. The animals were then grouped according to their watermaze performance and IO curves compared between good and poor learners. After tetanisation, there was a negative withinanimal correlation between learning and evoked potential size with weak test stimuli and a positive correlation with strong stimuli. The decline of LTP across the IO curve differed between good and poor spatial learners; the poor learners showed higher percentage potentiation with test stimuli close to zero intensity, but a faster decrease in LTP across the curves. The findings are therefore: (1) the measured amount of LTP declined systematically with increasing stimulus strength, and (2) the parameters of the decline correlated with spatial learning ability. These results raise two important issues. First, because measured LTP varied systematically across the IO curve, it appears that for quantitative analyses the widely used method of LTP measurement using a single test stimulus intensity risks missing significant features of the data. It is suggested that a measure be used that incorporates data from a range of stimulus intensities. Second, when such a measure is used there is a striking negative correlation of spatial learning ability with LTP. These apparently paradoxical results are discussed.
与海马突触长期增强相关的空间信息获取和遗忘率的年龄比较。
影响因子：
1.9
作者：
Barnes,CA;McNaughton,BL
通讯作者：
McNaughton,BL