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

Carli Domenico,Daniel Haggerty,Daoyun Ji,Xiang Mou

doi:10.1016/j.celrep.2021.109714

Abstract

Lysergic acid diethylamide (LSD) produces hallucinations, which are perceptions uncoupled from the external environment. How LSD alters neuronal activities invivo 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.

Highlights

The psychedelic drug lysergic acid diethylamide (LSD) is a potent hallucinogen that produces surreal hallucinations in humans, defined as subjective perceptions uncoupled from external environments (Liechti, 2017; Schmid et al, 2014)
Because LSD produces a mismatch between internal perception and external environment, we aimed to study whether the cognitive map in HP and the interaction between HP and visual cortex (VC) are altered by LSD in vivo
Increased firing rates around HT Because HT is considered a behavioral signature of 5HT2ARmediated hallucinations (Fantegrossi et al, 2008), we examined the behavior and neural activities surrounding HTs

Summary

Introduction

The psychedelic drug lysergic acid diethylamide (LSD) is a potent hallucinogen that produces surreal hallucinations in humans, defined as subjective perceptions uncoupled from external environments (Liechti, 2017; Schmid et al, 2014). 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 (Corne et al., 1963; Fantegrossi et al, 2008; Gonzalez-Maeso et al, 2007) or a head-bobbing motion in rabbits (Dave et al, 2004; Romano et al, 2010). We targeted neuronal firing activities, as well as local field potentials (LFPs), in the CA1 area of HP and VC in freely moving rats during their behavioral responses to LSD

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