A study on psychedelics reveals the strange behavior of neurons behind hallucination


HAllucinations are at the root of many neurological conditions, induced by a drug or not. Narcolepsy, schizophrenia and Alzheimer's are all associated with moments of visual perception of the unreal. Psychedelic drugs like LSD, of course, also cause hallucinations. But despite their frequency, scientists have been unable to explain the neural mechanisms that cause them. New search published Tuesday in Cell reports change that.

In an effort to understand how neurons react during a hallucination, a team of researchers, including Cristopher Niell, an associate professor of biology at the University of Oregon, administered hallucinogenic drugs to the mouse, and then examined their brain.

The team expected to see neurons running violently and signals mismatched. Instead, they found that the drug had caused a reduction of activity in the neurons of the visual cortex. In particular, says Niell, the information transmitted by these neurons have not changed. During hallucination, the strength of these signals decreases and their timing is changed.

Niell tells reverse that one or the other of these changes could contribute to the cause of hallucinations. A decrease in signaling strength could lead to a misinterpretation of visual data collected during observation in certain areas of the brain, while a change in timing could result in erroneous transmission of data to the patient. other parts of the brain.

These discoveries, Niell explains, provide a better understanding of the neurological and psychiatric disorders that lead to a disturbance of perception and cognition, such as schizophrenia.

"We hope to eventually bring this together to help understand in detail how the brain creates our representation of the world around us and how it is disrupted in altered states such as hallucinations," he says.

Activity in the visual cortex of the mouse in response to a psychedelic drug.

The team administered a hallucinogenic drug called DOI (2,5-dimethoxy-4-iodoamphetamine), which, like LSD and psilocybin, acts on serotonin 2A receptors. Unlike these drugs, it is not regulated by Appendix II.

After dosing, mice saw images on a screen while scientists measured responses in their brain using fine imaging techniques.

Most studies on hallucinations have been performed in humans using methods such as functional magnetic resonance imaging (fMRI). But these tests provide relatively low measures of brain activity in large areas of the brain. They give the impression that something in the brain is changing, but it's hard to measure what individual neurons do, Niell explains.

To study more closely the different neurons involved in hallucination, the team has taken advantage of recent advances in microscopy and electrical recording. This, says Niell, "is like the difference between listening to the roar of a crowd in a stadium and being able to hear the individual conversations of people in the crowd."

They observed that the neurons of hallucinatory mice exhibited impaired neuronal signal timing and decreased strength, despite the fact that overall cerebral signaling and visual cortex activity appeared to be identical to those before mouse. drug. This demonstrates that visual information processed in the brain is not different in itself; it is only the amplitude and timing of the modified signals.

Mouse neurons fire in response to a visual stimulus. The video has been accelerated 4 times in real time.

Niell and his colleagues, who specialize in visual processing, argue that these findings correspond to what we know about how the brain deals with visual information. When we see the world, we see the interpretation of the brain of the visual data that we absorb through the eyes. Hallucinations are what happens when the brain interprets and devalues ​​this coded information. Dreams are an analog of hallucinations: they are also sequences of vivid images that we can process, despite the absence of real visual signals.

Niell is careful to say that this study is primarily intended to stimulate work. It is a fundamental element in the understanding of hallucinations, but does not explain the phenomenon in its entirety. First, although DOI acts as a hallucinogen in humans and binds to the same serotonin receptors as all psychedelics in mice, we can not say for sure what a hallucination of a mouse looks like , thus limiting the applicability of the study to the human brain. And although they have observed changes in the brain of hallucinating mice, they can not tell which neural circuits are affected because the drug passes throughout the brain.

Nevertheless, the study goes in the right direction: given the recent reappearance of the use of psychedelic drugs to treat mental disorders, scientists are trying to understand what happens when the serotonin 2A receptors are altered and the hallucinated brain.


Sensory perception comes from the integration of representations of the world guided by the outside and the inside. A disruption of the balance of these representations can lead to deficits of perception and hallucinations. The serotonin-2A receptor (5-HT2AR) is associated with such alterations of perception, both in its role in schizophrenia and in the action of hallucinogenic drugs. Despite this powerful influence on perception, relatively little is known about the influence of serotonergic hallucinogens on sensory processing in the neocortex. Using wide-field and two-photon calcium imaging and single-unit electrophysiology in awake mice, we found that administration of the selective 5-HT2AR hallucinogenic agonist resulted in a marked reduction in amplitude. visual response and suppression of the surrounding in the primary visual cortex, as well as disturbed temporal dynamics. However, the basic retinotopic organization, the tuning properties and the structure of the receptor field remain intact. Our results corroborate models of hallucinations in which a reduction of the ascending sensory drive is a key factor in altering perception.

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