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Hallucinating mice bring us one step closer to what's going on in the brain

<img src = "https://cdn.arstechnica.net/wp-content/uploads/2019/03/mouseTOP2-800×529.jpg" alt = "Dumbo and Timothy Q. Mouse hallucinate pink elephants in a famous parade animated sequence from Disney's Dumbo (1941) Scientists have mapped mouse neurons under the influence of a hallucinogen for a new study. "/>
Enlarge / Dumbo and Timothy Q. Mouse hallucinate pink elephants on a parade in a famous animation sequence from Disney's Dumbo (1941). Scientists have mapped neurons from mice under the influence of a hallucinogen for a new study.

People who are under the influence of hallucinogenic drugs such as LSD often experience vivid visual hallucinations. But what exactly happens in the brain to trigger such a state remains a mystery. According to a recent work in Cell Reports experiments with mice under the influence of a hallucinogenic drug showed signs that hallucinations can be triggered by decreased signaling between neurons in the visual cortex along with changes in the timing they fire.

This, according to co-author Cris Niell, a neuroscientist at the University of Oregon, may seem counterintuitive. "One could assume that visual hallucinations are due to neurons in the brain firing like crazy or through inappropriate signals," he said. "We were surprised to find that a hallucinogenic drug instead led to a reduction in activity in the visual cortex, but in the context of visual processing, it made sense."

In short, the brain can cause an over-interpretation of information deficiency. For example, when we dream, there are no visual signals that enter the brain, and yet the brain still produces visual patterns.

The results of his team can help to promote the potential of such drugs for the treatment of anxiety, depression or schizophrenia (which is often the case) produces auditory and / or visual hallucinations). Albert Hofmann first synthesized LSD in 1938 when working for the pharmaceutical company Sandoz. Originally it was used under the trade name Delysid for the treatment of anxiety and depression. More than 1,000 research papers were published between 1950 and 1965, until the 1970 Act on Controlled Substances made it nearly impossible to obtain government funding or the medicines needed for study studies. After that, LSD-related research pretty much stopped, but in the past 15 years, hallucinogenic drugs have made a comeback in research circles.

Change in the Receiver in the Brain

After LSDs had experienced hallucinatory effects on the infamous "bike" day "in April 1943, Hofmann speculated that the drug had biochemically altered the" recipient "of the brain and set it to a different wavelength. In his book, The Doors of Perception Aldous Huxley suggested that LSD works by countering what he called a "reducing valve" in the brain that typically restricts our perceptions. those who are stumbled with acid receive more sensory input than usual due to a decrease in brain activity, and several previous brain imaging studies with humans have shown that psychedelics interfere with normal brain activity and spur the random firing of neurons in the visual cortex. [19659004] For example, a study from the laboratory of Imperial College by Neuropsychopharmako examined In 2012, David Nutt in England took the brains of 30 subjects (all experienced users of psychedelics) while under the influence of psilocybin – also known as magic mushrooms. The lab then compared them to scans after the subjects took a saltwater placebo. (Side note: Nutt was dismissed in 2009 from his post as a UK Drug Commissioner on grounds of misapprehension because he argued that psychedelic drugs had been wrongly stigmatized.)

  A research mouse with a super-light electrode monitoring the neurons in her brain. It is just one of several recently developed techniques for rendering neurons much more detailed.
Enlarge / A research mouse with a super-light electrode that monitors the neurons in their brains. It is just one of several recently developed techniques to present neurons in more detail.

Ian Allen / Condé Nast / Getty Images

Nutt and his colleagues found that all brain activity had decreased in the so-called "standard mode". a collection of highly networked neural networks that normally shoot together when the brain is at rest. Psilocybin interfered with this synchronization, which could lead to the dissociative aspects of hallucinogenic drugs – the often-reported sense of a decaying self or self-esteem.

In 2016, Nutt et al . published the results of a second fMRI study, this time with subjects under LSD influence, compared to a placebo. Once again, in standard mode, there was less synchronization (general brain activity) between the neurons. However, they also found that certain different regions of the brain that normally do not communicate with each other did so under the influence of LSD, especially in the visual cortex. This could explain the vivid hallucinations experienced by people stumbling upon acidity. The effect, however, seems to be separate from ego dissolution; You can experience one without the other.

Another study from the following year in Scientific Reports found a sudden increase in brain activity among subjects under the influence of psychedelic drugs. This is a possible evidence of an elevated state of consciousness, which is often associated with psychedelics.

"People tend to associate expressions such as" a higher state of consciousness "with hippie language and mystic nonsense," co-author Robin Carhart-Harris of Imperial College narrated The Guardian . "This may be the beginning of demystification and shows its physiological and biological foundations, perhaps this is a neuronal signature of mental opening."

"[It’s]" as you could hear the rushing of the crowd in a stadium or being single talk. "

Earlier this year, a Swiss research team used MRI imaging to track the brain under the influence of acid. The researchers' findings support the idea that hallucinogens cause the system to collapse, allowing the brain to understand what information comes from the real world and what is generated by the brain itself. Ars & # 039; John Timmer reported in February: "Instead of a general flood of corticals, they found that a limited number of specific regions showed increased activity, suggesting that the hallucinogenic-induced states are different from conditions such as anesthesia and sleep distinguish, which cause changes in the cortex widespread. "

Mice on acid

Nutt and others . His research was certainly Niell's thoughts when he began his experiments with mice, although the focus of his research was primarily on how visual perception works in general. He recognized that the study of hallucinations in which visual perception is disturbed would be a good exploratory mechanism, especially if he could measure what was happening on the scale of individual neurons.

while Niell's mouse study measures how the mouse's brain responds to certain sensory stimuli, in this case visual input. In addition, the fMRI measures the activity of millions of neurons that are added together, and it measures the changes in blood flow technically – more like an indirect measure of brain activity in humans. In contrast, Niell's group directly measured the activity of hundreds of individual neurons simultaneously.

"This is the difference between listening to viewers in a stadium and listening to one-on-one conversations within the audience." Niell said.

Because LSD and similar hallucinogens are classified as category I substances by the US Drug Enforcement Agency, and therefore difficult to obtain even for laboratory use, Niell and colleagues used a chemically similar drug called DOI (4-iodo-2 , 5-dimethoxyphenylisopropylamin). This concerns the same serotonin 2A receptors as LSD and psilocybin.

How could you tell if the mice were hallucinating? Unlike humans, mice can not describe their experience of tripping. "We have indirect opportunities to investigate what they see," Niell said. These pathways usually involve the mice running against a reward (eg food) against a vertical line or a horizontal line. Mice under the influence can twitch their heads or move their paws in an unusual way.

The researchers then pushed the stunned mice onto a small impeller and showed them various images on a computer screen, monitoring their brain response with both calcium and calcium. Unit Electrophysiology. In this way, "Not only do you know what each neuron says, but how its interactions change," Niell said. They found that the usual burst of activity in response to a visual stimulus is suppressed, altering the timing of the information, which in turn may affect the way in which other regions of the brain reach it.

There Was No Change In the signals sent to the visual cortex, the team concluded that hallucinations are more likely to be due to how the sensory information is interpreted than what it does. "Understanding what's going on in the world is a balance of information and interpretation of that information," Niell said. "If you put less emphasis on what's going on around you and then over-interpret it, it could lead to hallucinations."

DOI: Cell Reports 2019. 10.1016 / j.celrep. 2019.02.104 (via DOIs).

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