Department of Psychological and Brain Sciences, 1101 E 10th St, Bloomington, Indiana, 47405.
Center for Memory and Brain, Department of Psychology, Boston University, 2 Cummington Mall, Boston, Massachusetts, 02215.
Hippocampus. 2017 Oct;27(10):1069-1082. doi: 10.1002/hipo.22753. Epub 2017 Jul 17.
New memory formation depends on both the hippocampus and modulatory effects of acetylcholine. The mechanism by which acetylcholine levels in the hippocampus enable new encoding remains poorly understood. Here, we tested the hypothesis that cholinergic modulation supports memory formation by leading to structured spike timing in the hippocampus. Specifically, we tested if phase precession in dorsal CA1 was reduced under the influence of a systemic cholinergic antagonist. Unit and field potential were recorded from the dorsal CA1 of rats as they completed laps on a circular track for food rewards before and during the influence of the systemically administered acetylcholine muscarinic receptor antagonist scopolamine. We found that scopolamine significantly reduced phase precession of spiking relative to the field theta, and that this was due to a decrease in the frequency of the spiking rhythmicity. We also found that the correlation between position and theta phase was significantly reduced. This effect was not due to changes in spatial tuning as tuning remained stable for those cells analyzed. Similarly, it was not due to changes in lap-to-lap reliability of spiking onset or offset relative to either position or phase as the reliability did not decrease following scopolamine administration. These findings support the hypothesis that memory impairments that follow muscarinic blockade are the result of degraded spike timing in the hippocampus.
新记忆的形成既依赖于海马体，也依赖于乙酰胆碱的调节作用。乙酰胆碱在海马体中的水平如何使新的编码成为可能，这一机制仍未被很好地理解。在这里，我们检验了这样一个假设，即胆碱能调节通过在海马体中产生有组织的尖峰定时来支持记忆形成。具体来说，我们测试了在全身给予乙酰胆碱毒蕈碱受体拮抗剂东莨菪碱的影响下，背侧 CA1 中的相位超前是否会减少。在大鼠完成圆形轨迹上的食物奖励任务时，我们从背侧 CA1 记录了单位和场电位，在此之前和期间，系统给予了东莨菪碱。我们发现，东莨菪碱显著降低了相对于场 theta 的尖峰相位超前，这是由于尖峰节律性的频率降低所致。我们还发现，位置和 theta 相位之间的相关性显著降低。这种效应不是由于空间调谐的变化引起的，因为对于那些被分析的细胞，调谐保持稳定。同样，它也不是由于尖峰起始或结束相对于位置或相位的 lap-to-lap 可靠性的变化引起的，因为在给予东莨菪碱后，可靠性并没有降低。这些发现支持了这样一个假设，即 muscarinic 阻断后出现的记忆损伤是由于海马体中尖峰定时的退化。
