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

Summary

LSD reduces the firing rates and directionality of hippocampal place cells in rats running on a familiar track, while also decreasing their interaction with visual cortical neurons. During head-twitching, associated with hallucination-like states, both hippocampal and visual cortical neurons show increased firing rates. When immobile, LSD enhances cortical firing synchrony but dampens hippocampal-cortical interactions, leading to degraded internal representations that are disconnected from external sensory input.

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.

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