LSD Alters Hippocampal‐Cortical Interactions in Freely Moving Rats
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Lysergic acid diethylamide ﴾LSD﴿ is a potent hallucinogen, producing percepts that are incongruent from the external world. While hallucinogenic drugs are increasingly being used and studied for therapeutic purposes, little is understood about their direct effect on neural activity. Because CA1 of hippocampus ﴾HC﴿ and visual cortex ﴾VC﴿ are crucial in constructing an internal map of the external world, we recorded from these two regions using in vivo electrophysiology tetrode recordings while rats ran on a track for a food reward in two running sessions separated by sleep. Prior to the first running session, rats were administered saline. Before the second and final running session, we administered a low or high dose of LSD or control solution. The control consisted of either saline, the 5ht2a‐receptor antagonist M100907, or LSD and M100907 combined. Our results found that with LSD, rats often slowed their movement and displayed the characteristic head twitch behavior seen with rodents given hallucinogenic 5ht2aR agonists. Furthermore, these rats retained place cell spatial information but dramatically reduced in hippocampal firing rate while cortex maintained similar rates but altered firing characteristics compared to control conditions. Rats became immobile more rapidly and more frequently with LSD, and they often drifted quickly into a wake‐to‐sleep limbo state with highly synchronized cortical activity. While VC neurons correlated with those in CA1 during running and rest following control injections, we observed reduced coactivity with LSD suggesting a dampened communication between the regions. In this study, rats retain spatial cognition with an overall preserved map in hippocampus, but we demonstrate that the representation is still atypical with reduced firing rate and also reduced specificity seen in bidirectional place fields. VC and HC also appear to miscommunicate with altered paired coactivity and quick transitions into other functional states like the sleep‐to‐wake high voltage spike state observed in cortex during brief stops. This miscommunication may contribute to the observed degraded representations of the environment in hippocampus and give insights into LSD‐produced abnormal perceptions.
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