Neuroscience Blog

Written by Brett J. Weiss

September 26, 2021

Baylor scientists show a brain region producing memory-based depictions of the environment miscommunicate with a visual region in hallucinating LSD-injected rats.

Highlights

• A brain region that encodes and retrieves memories called the hippocampus shows weak and disorganized communication with a visual sensory region in rats given LSD.
• Brain activity in the visual sensory cortex resembles that displayed during the wakefulness to sleep transition, indicating dreamlike properties to the hallucinations.
• Memory circuit and visual sensory miscommunication may produce abnormal mental representations of the external environment during dreamlike hallucinations.

Hallucinations encompass internal perceptions that don’t align with what other people discern from the external environment. The powerful hallucinogenic drug lysergic acid diethylamide (LSD) is, needless to say, well-renowned for triggering these mind-bending states chockfull of phantasmic observations. Although some brain studies in humans have pointed to LSD producing hallucinations by altering communication across brain regions, measuring neuronal activation to uncover details has been impossible. So, researchers have turned to rats given LSD to learn more about how the potent drug affects brain function.

Ji and colleagues from the Baylor College of Medicine published a study in Cell Reports where they showed that LSD facilitates anomalous communication between memory-based and visual sensory brain regions in rats. The Baylor-based research team provided new details indicating that weakened communication between the brain’s memory circuits and visual sensory areas may generate distorted mental representations of the external environment during hallucinations. Figuring out how exactly LSD alters brain function can help researchers uncover the basis for the formation of perceptions and how our memories contribute to them. Such research can apply to alleviating conditions like post-traumatic stress disorder (PTSD) and addictions, with memories and perceptions playing crucial roles in driving these ailments.

Rat Behavior Associated with Hallucinations

So, how do we know the rats studied were under LSD’s influence and that we can rely on LSD rat studies to gain insight into how the human brain functions while hallucinating? Well, rats twitch their heads while experiencing the effects of LSD. In fact, when given molecules that activate the brain receptor that LSD activates, the 5-hydroxytryptamine-2A receptor, rats also twitch their heads, but blocking the receptor stops the twitching. Because of these findings, researchers associate rat head twitching with hallucinating.

LSD Disorients Location-Sensitive Neuron Firing

To find out what kinds of effects LSD has on neuron activity in rats, Ji and colleagues had rats run through a maze they were accustomed to while measuring neurons firing. Since studies in humans have suggested LSD alters communication between memory-related and visual regions, Ji and colleagues looked at neurons in the hippocampus and visual cortex. Their measurements indicated that LSD changed when the cells fired, meaning that they would typically fire only when the rat remembered traveling a certain direction but changed their directionality. These findings suggest some degree of memory failure or disorientation.

LSD Impedes Memory and Sensory Visual Brain Region Communication

Ji and colleagues then tried to find whether the functionally-linked hippocampus and visual cortex were communicating properly as they do during memory formation and retrieval. They found that LSD substantially hampered communication between the regions based on reduced correlation between their neurons’ firing rates. These results indicate that the altered directionality of hippocampal neurons and miscommunication between the two brain regions may play roles in distorted mental representations while hallucinating.

Wakefulness to Sleep Brainwaves Induced by LSD

Ji and colleagues then measured brainwave activity to find out what brain activity distinguishes hallucinations from typical wakefulness. The research team observed a higher prevalence of brainwaves called high voltage spikes (HVS) that associate with dreamlike states of mind during the waking to sleep transition. They then speculated that this dreamlike brain state may contribute to the altered perceptions that occur while hallucinating.

“Overall, our work reveals neurophysiological alterations that can advance our understanding of how LSD produces its powerful reality-altering effects,” said Ji and colleagues in their publication. They went on to say that the reduced communicative interactions between the memory-based hippocampus and the visual cortex leads to a spatial representation degradation. The brain’s mapping of the external environment then becomes different from the surrounding environment. On top of that, with the activation of the dreamlike wakefulness to sleep transition state, the brain can generate mental imagery without visual sensory input.

Is this Research Translatable?

The research from Ji and colleagues’ study adds to our knowledge of how LSD influences the mammalian brain, but what medical impact it will make remains unclear. There are a multitude of human clinical trials currently underway testing LSD’s effects on conditions ranging from cluster headaches to depression, so it will likely have some application. Maybe results from the study that help us understand how the brain functions during hallucinatory states will help researchers figure out how to form better memories while learning or erase traumatic memories that impede our abilities to function.

Story Source

Domenico C, Haggerty D, Mou X, Ji D. LSD degrades hippocampal spatial representations and suppresses hippocampal-visual cortical interactions. Cell Rep. 2021 Sep 14;36(11):109714. doi: 10.1016/j.celrep.2021.109714. PMID: 34525364.