Psilocybin, a psychedelic substance, has long been known for its ability to alter perception and cognition, often leaving users disoriented. A new study published in the European Journal of Neuroscience investigates how the drug affects brain activity at the level of individual neurons. By studying mice navigating virtual environments, researchers found that psilocybin interferes with the brain’s ability to encode spatial information, showing that people under the influence of psilocybin experience a distorted sense of space. We found out why this is so common.
Psilocybin is a natural compound found in certain types of mushrooms, also known as “magic mushrooms.” When ingested, it is converted into psilocin in the body, which acts on serotonin receptors in the brain, specifically serotonin 2A receptors. Psilocybin is known for its psychedelic effects, including changes in perception, mood, and cognition, and the experience of significant changes in the sense of self, space, and time. Psilocybin has traditionally been used in religious or spiritual rituals, but has attracted significant scientific interest in recent years due to its potential therapeutic effects on mental health conditions such as depression, anxiety, and post-traumatic stress disorder. are collecting.
Researchers are particularly interested in understanding how psilocybin works at a biological level. Studies using human brain imaging have shown that psychedelics like psilocybin disrupt normal communication patterns between different brain regions. These disruptions are thought to cause the altered state of consciousness that people experience when using drugs.
However, much of the existing research has been conducted using indirect means such as functional magnetic resonance imaging, which provides a broad overview of brain activity but does not provide insight into how individual neurons are affected. We do not have detailed information on whether or not you will receive it. This is where studies using such animal models come into play. This will allow scientists to investigate the effects of psychedelics at a cellular level, allowing them to better understand how these substances affect brain function.
We focused specifically on the retrosplenial cortex, a brain region important for spatial awareness and navigation. Some neurons in this region, like the “place cells” of the hippocampus, are important for responding to specific locations in the environment and forming mental maps of the surroundings. The researchers wanted to see how psilocybin affects this spatial encoding, which could potentially explain why people taking psychedelic drugs often report altered sense of position. I was there.
“Psychedelics have significant effects on mental function, but we still don’t understand how they affect the information processing carried out by groups of neurons,” said study author and University of Lethbridge researcher. said Aaron J. Gruber, professor of neuroscience at . “Advances in cell-level imaging and computational analysis in animals now allow us to study how drugs affect the dynamic encoding of information in neuronal populations. We recorded neurons in brain regions that are important for forming expressions.
The study used 10 adult mice that were genetically modified to allow visualization of neural activity using imaging techniques. Each mouse was trained to run on a treadmill with its head in a fixed position and moved on a belt with specific tactile, visual, and auditory cues. The treadmill is designed to simulate a virtual environment and rewards you for completing laps. This setup allowed the researchers to record and analyze the activity of neurons in the retrosplenial cortex as the mice performed the task.
After training the mice, the researchers conducted imaging sessions to monitor brain activity. They recorded each mouse’s baseline neural activity and then administered psilocybin or saline. Psilocybin was administered at a dose of 15 mg/kg, and the mice were recorded again to compare neural activity before and after drug administration. Some studies pretreated mice with a drug called ketanserin, which blocks serotonin 2A receptors (a key receptor involved in psychedelic effects), to see if it altered the effects of psilocybin.
Neural activity was measured using two-photon imaging, an advanced technique that allows researchers to observe the activity of hundreds of neurons simultaneously. The researchers focused on how neurons encode the mouse’s position on the treadmill belt and analyzed the stability of this spatial encoding across trials.
The results showed that psilocybin had a significant effect on neurons in the retrosplenial cortex. Typically, when a mouse passes a specific spot on the treadmill belt, many neurons in this brain area become active. However, after psilocybin administration, the specificity of these neurons for a particular location was significantly reduced. This meant that neurons were no longer reliably activated in certain locations, leading to a reduction in the brain’s ability to encode spatial information.
Moreover, the stability of this location-related neural activity across trials was also reduced under the influence of psilocybin. In other words, there was less consistency in how neurons responded to specific locations from one lap of the treadmill to the next. This instability in spatial encoding may reflect feelings of disorientation and changes in spatial perception that people often experience when using psychedelics.
Another important finding was that psilocybin reduces coordination, or functional correlation, between neurons. The synchrony of neurons that normally fire together when encoding spatial information was reduced, suggesting that psilocybin disrupted normal communication patterns within the retrosplenial cortex. This reduction in coordinated neural activity supports the idea that psychedelics increase the randomness, or entropy, of neural signaling.
“Psilocybin administration temporarily impaired the coordinated brain activity that tracks the animal’s position in its environment,” Gruber told Scipost. “If something similar happens in humans, it may help explain the altered sense of time and space that is frequently reported during psychedelic use.”
The role of serotonin in these effects was confirmed by experiments involving ketanserin. Pretreating mice with ketanserin before psilocybin administration significantly prevented changes in neural activity patterns. This indicates that serotonin 2A receptors play an important role in mediating the effects of psilocybin on the brain.
“Several recent high-profile reports have shown that psychedelics promote synapse formation,” Gruber said. “We therefore expected that the high dose of psilocybin we used would cause permanent changes in information processing that could be detected several days after the last dose. We found no evidence of permanent changes. This suggests that changes in synaptic structure had very subtle effects on the neocortical areas we investigated.”
“We previously tested the effects of the non-classical psychedelic ibogaine in the same task and setting. The effects of ibogaine and psilocybin were qualitatively similar, but ibogaine had a much more potent acute Ibogaine also had no apparent long-term effects on the brain activity we studied.
Although this study reveals how psilocybin affects neural activity in specific brain regions, there are some limitations to consider. First, the experiment was conducted on mice, so the results may not be completely applicable to humans. Although the retrosplenial cortex plays a similar role in spatial navigation across species, the human psychedelic experience is more complex and involves higher cognitive functions beyond basic spatial encoding.
The researchers now plan to investigate how psilocybin affects other brain regions, particularly those involved in motivation and decision-making associated with conditions such as depression. Understanding the pervasive effects that psychedelic substances have on brain networks may provide valuable insight into how these substances may be used in therapeutic settings to help treat mental health disorders.
“This study has several goals,” Gruber explained. “One is to use the profound effects of psychedelics on perception and brain function as a tool for understanding how the brain normally processes information. We also hope that psychedelics may be linked to major depressive disorder. We also want to understand how it can help treat diseases such as depression. Other brain regions more directly associated with motivational factors will also be investigated.”
The study, “Psilocybin reduces functional correlation and encoding of spatial information by neurons in the mouse retrosplenial cortex,” was published by Victorita E. Ivan, David P. Tomàs-Cuesta, Ingrid M. Esteves, Artur Luczak, Majid Mohajerani, and Bruce Written by L. McNaughton, Aaron J. Gruber.
