Lysergic acid diethylamide (LSD) produces hallucinations, which are perceptions uncoupled from the external environment. How LSD alters neuronal activities in vivo that underlie abnormal perceptions is unknown. Here, we show that when rats run along a familiar track, hippocampal place cells under LSD reduce their firing rates, their directionality, and their interaction with visual cortical neurons. However, both hippocampal and visual cortical neurons temporarily increase firing rates during head-twitching, a behavioral signature of a hallucination-like state in rodents. When rats are immobile on the track, LSD enhances cortical firing synchrony in a state similar to the wakefulness-to-sleep transition, during which the hippocampal-cortical interaction remains dampened while hippocampal awake reactivation is maintained. Our results suggest that LSD suppresses hippocampal-cortical interactions during active behavior and during immobility, leading to internal hippocampal representations that are degraded and isolated from external sensory input. These effects may contribute to LSD-produced abnormal perceptions.

麦角酰二乙胺 (LSD) 会产生幻觉，即与外部环境脱钩的知觉。LSD 如何改变体内神经元活动异常感知的基础是未知的。在这里，我们表明当老鼠沿着熟悉的轨道奔跑时，LSD 作用下的海马体位置细胞会降低它们的放电率、方向性以及它们与视觉皮层神经元的相互作用。然而，海马体和视觉皮层神经元在头部抽搐期间会暂时增加放电率，这是啮齿类动物幻觉状态的行为特征。当大鼠在跑道上不动时，LSD 会在类似于清醒到睡眠过渡的状态下增强皮层放电同步，在此期间海马-皮层相互作用会受到抑制，而海马清醒状态的重新激活会得到维持。我们的结果表明 LSD 在主动行为和不动期间抑制海马皮质相互作用，导致内部海马体表征退化并与外部感觉输入隔离。这些影响可能导致 LSD 产生异常感知。