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

Introduction

Lysergic acid diethylamide (LSD) is a potent hallucinogen that produces perceptions uncoupled from the external environment. Prior human imaging work indicates LSD and related hallucinogens alter activity in prefrontal, visual cortical and hippocampal regions and disrupt functional connectivity among them, but the effects of LSD on single‑neuron firing in these areas during behaviour are unknown. Rodent models permit simultaneous in vivo recording of spikes and local field potentials (LFPs) during behaviour, and rodents reliably show a head‑twitch (HT) response to hallucinogens that depends on 5HT2A receptor activation and involves the hippocampus and visual cortex. C. and colleagues therefore recorded spiking and LFP activity from hippocampal CA1 and visual cortical (VC) regions in freely moving rats running a familiar C‑shaped track. The study aimed to determine how systemic LSD (two doses) alters CA1 place‑cell firing, population spatial representations, CA1–VC interactions during active running and immobility, and the relationship of neural changes to behaviour (lap rate, speed, immobility, HTs). The authors also tested whether a 5HT2A antagonist (M100907) blocks LSD effects, and examined LFP events (ripples, high‑voltage spikes) that accompany immobility.