Department of Physiology, University of Toronto, Toronto, Canada.
Program in Neurosciences and Mental Health, Hospital for Sick Children, University Avenue, Toronto, Canada.
Elife. 2017 Sep 29;6:e27868. doi: 10.7554/eLife.27868.
Following learning, increased coupling between spindle oscillations in the medial prefrontal cortex (mPFC) and ripple oscillations in the hippocampus is thought to underlie memory consolidation. However, whether learning-induced increases in ripple-spindle coupling are necessary for successful memory consolidation has not been tested directly. In order to decouple ripple-spindle oscillations, here we chemogenetically inhibited parvalbumin-positive (PV) interneurons, since their activity is important for regulating the timing of spiking activity during oscillations. We found that contextual fear conditioning increased ripple-spindle coupling in mice. However, inhibition of PV cells in either CA1 or mPFC eliminated this learning-induced increase in ripple-spindle coupling without affecting ripple or spindle incidence. Consistent with the hypothesized importance of ripple-spindle coupling in memory consolidation, post-training inhibition of PV cells disrupted contextual fear memory consolidation. These results indicate that successful memory consolidation requires coherent hippocampal-neocortical communication mediated by PV cells.
学习后，被认为内侧前额叶皮层（mPFC）中的纺锤波振荡和海马中的涟漪波振荡之间的耦合增加，是记忆巩固的基础。然而，学习诱导的涟漪-纺锤波耦合增加是否对于成功的记忆巩固是必需的，尚未直接进行测试。为了解耦涟漪-纺锤波振荡，我们化学遗传学抑制了 Parvalbumin 阳性（PV）中间神经元，因为它们的活动对于调节振荡期间的尖峰活动的时间很重要。我们发现，情境性恐惧条件作用增加了小鼠的涟漪-纺锤波耦合。然而，无论是 CA1 还是 mPFC 中的 PV 细胞的抑制，都消除了这种学习诱导的涟漪-纺锤波耦合的增加，而不影响涟漪波或纺锤波的发生。与假设的涟漪-纺锤波耦合在记忆巩固中的重要性一致，训练后抑制 PV 细胞会破坏情境性恐惧记忆的巩固。这些结果表明，成功的记忆巩固需要由 PV 细胞介导的海马-新皮层通讯的协调。
