Brain oscillations have been hypothesized to support cognitive function by coordinating spike timing within and across brain regions, yet it is often not known when timing is either critical for neural computations or an epiphenomenon. The entorhinal cortex and hippocampus are necessary for learning and memory and exhibit prominent theta oscillations (6–9 Hz), which are controlled by pacemaker cells in the medial septal area. Here we show that entorhinal and hippocampal neuronal activity patterns were strongly entrained by rhythmic optical stimulation of parvalbumin-positive medial septal area neurons in mice. Despite strong entrainment, memory impairments in a spatial working memory task were not observed with pacing frequencies at or below the endogenous theta frequency and only emerged at frequencies ≥10 Hz, and specifically when pacing was targeted to maze segments where encoding occurs. Neural computations during the encoding phase were therefore selectively disrupted by perturbations of the timing of neuronal firing patterns.

大脑振荡被假设为通过协调大脑区域内和跨大脑区域的尖峰时间来支持认知功能，但通常不知道时间何时对神经计算或附带现象至关重要。内嗅皮层和海马体是学习和记忆所必需的，并表现出显着的 theta 振荡 (6–9 Hz)，由内侧间隔区域的起搏细胞控制。在这里，我们表明内嗅和海马神经元活动模式受到小鼠小清蛋白阳性内侧间隔区神经元的节律性光刺激的强烈影响。尽管有很强的夹带作用，但在起搏频率等于或低于内源性 theta 频率时，并未观察到空间工作记忆任务中的记忆障碍，并且仅在频率≥10 Hz 时出现，特别是当起搏被定位到发生编码的迷宫段时。因此，编码阶段的神经计算被神经元放电模式时间的扰动选择性地破坏。