LSD degrades hippocampal spatial representations and suppresses hippocampal-visual cortical interactions

Lysergic acid diethylamide (LSD) reduces firing rates, directionality, and interaction with visual cortical neurons in hippocampal place cells of rats running along a familiar track. During head-twitching—a behavioral sign of a hallucination-like state—both hippocampal and visual cortical neurons temporarily increase firing rates. When rats are immobile, LSD enhances cortical firing synchrony similar to the wakefulness-to-sleep transition, while hippocampal-cortical interaction remains dampened but hippocampal awake reactivation persists. These findings suggest LSD suppresses hippocampal-cortical interactions during active behavior and immobility, degrading and isolating internal hippocampal representations from external sensory input, which may contribute to abnormal perceptions.

Study at a glance

Abstract

Summary: 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.