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

The authors of this animal model study (2021) examined the effects of LSD on rats trained to run along a familiar track. Neuronal firing rates decrease under LSD which influences behavior.

Abstract

“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.”

Authors: Carli Domenico, Daniel Haggerty, Xiang Mou & Daoyun Ji

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

Introduction

LSD is a potent hallucinogen that produces surreal hallucinations in humans. Previous studies in rats have shown that LSD alters neuronal activities in the prefrontal cortex, visual cortex, and hippocampus, as well as their functional connections with other regions, during resting and during active tasks.

Rodents display a unique response to LSD and similar hallucinogens called head-twitching (HT), which is a brief, rapid shake of the head in rats and mice or a head-bobbing motion in rabbits. HT requires activation of the serotonin 5-hydroxytryptamine-2-A receptor (5HT2AR), which can be blocked by specific 5HT2AR antagonists.

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