Mouse study examines the underpinnings of hallucinations

March 26, 2019

Hallucinations result in dramatic disruptions in perception and cognition, but the changes in brain activity that underlie such alterations are not well understood. In a study publishing March 26 in the journal Cell Reports, researchers looked at how a hallucinogenic drug impacts the brains of mice at the level of individual neurons. They found that visual hallucinations may be triggered by a reduction in signaling within the visual cortex, rather than an increase, and by altered timing of when the neurons fire.

In addition to helping us understand how hallucinogens affect brain function, the findings also have implications for figuring out the neurological underpinnings in disorders like schizophrenia that are characterized by hallucinations.

"You might expect visual hallucinations would result from neurons in the brain firing like crazy, or by mismatched signals. We were surprised to find that a hallucinogenic drug instead led to a reduction of activity in the visual cortex," says senior author Cris Niell, an associate professor and member of the Institute of Neuroscience at the University of Oregon.

"In the context of visual processing, though, it made sense," he adds. "Understanding what's happening in the world is a balance of taking in information and your interpretation of that information. If you're putting less weight on what's going on around you but then overinterpreting it, that could lead to hallucinations." One example of this is the vivid images that are often seen in dreams, despite no visual signals coming in to the brain; another example is the hallucinations experienced after spending long periods of time in the dark.

"We're interested in understanding how we create representations of the world using vision," he says. "In many areas of biology, one of the best ways to study a process is to observe what happens when it's perturbed." The researchers, including graduate student Angie Michaiel and postdoctoral fellow Phil Parker, decided that inducing hallucinations would be a good way to investigate disrupted visual signals in the brain.

The drug given to the mice in the study is called DOI (4-iodo-2,5-dimethoxyphenylisopropylamine) and is often used in animal studies. Like other hallucinogenic drugs, including LSD and psilocybin, it acts on serotonin 2A receptors. But unlike those other drugs, it's not regulated by the Drug Enforcement Agency as a Schedule 1 drug, making it more accessible for research purposes.

After being given the drug, the mice were shown images on a screen. The researchers used calcium imaging and single-unit electrophysiology to monitor the responses in their brains and look at which neurons were affected by both the visual stimulation and the drug. They observed that there was an alteration in timing in the neurons, which was accompanied by a reduction in signaling. The fact that the mice were awake was significant: Much of the previous research on the effects of activating serotonin 2A receptors in the brain has been done in animals that were anesthetized.

The researchers were also able to confirm that the overall signals being sent, and organization of brain activity across the visual cortex, was similar to what is seen in the absence of the drug. This suggests the visual information being conveyed to the brain is not changed--it is just reduced in amplitude and altered in timing. These types of measurements are not accessible in data obtained from neuroimaging studies in humans.

There are limitations to studying visual hallucinations in animal models because animals can't directly report what they're seeing. But research has shown that drugs that cause hallucinations in humans cause reliable movement changes in mice, such as head twitches and unusual paw movements, suggesting that they similarly affect brain function. Future experiments will examine the ability of mice to make visual discriminations, which could potentially reveal whether perception is altered.

"I don't feel like we've necessarily found the smoking gun for the entire underlying cause of hallucinations, but this is likely to be a piece of it," Niell concludes. "The data we've collected will provide a foundation for additional studies going forward. In particular, we plan to use genetic manipulation to study particular parts of this circuit in more detail." Additionally, because the serotonin 2A receptor is known to play a role in schizophrenia, the investigators say it may be possible to apply these findings toward gaining a better understanding of what's happening in the brain with that disease.
This work was supported by the National Institutes of Health.

Cell Reports, Michaiel et al.: "A hallucinogenic serotonin-2A receptor agonist reduces visual response gain and alters temporal dynamics in mouse V1"

Cell Reports (@CellReports), published by Cell Press, is a weekly open-access journal that publishes high-quality papers across the entire life sciences spectrum. The journal features reports, articles, and resources that provide new biological insights, are thought-provoking, and/or are examples of cutting-edge research. Visit: To receive Cell Press media alerts, contact

Cell Press

Related Neurons Articles from Brightsurf:

Paying attention to the neurons behind our alertness
The neurons of layer 6 - the deepest layer of the cortex - were examined by researchers from the Okinawa Institute of Science and Technology Graduate University to uncover how they react to sensory stimulation in different behavioral states.

Trying to listen to the signal from neurons
Toyohashi University of Technology has developed a coaxial cable-inspired needle-electrode.

A mechanical way to stimulate neurons
Magnetic nanodiscs can be activated by an external magnetic field, providing a research tool for studying neural responses.

Extraordinary regeneration of neurons in zebrafish
Biologists from the University of Bayreuth have discovered a uniquely rapid form of regeneration in injured neurons and their function in the central nervous system of zebrafish.

Dopamine neurons mull over your options
Researchers at the University of Tsukuba have found that dopamine neurons in the brain can represent the decision-making process when making economic choices.

Neurons thrive even when malnourished
When animal, insect or human embryos grow in a malnourished environment, their developing nervous systems get first pick of any available nutrients so that new neurons can be made.

The first 3D map of the heart's neurons
An interdisciplinary research team establishes a new technological pipeline to build a 3D map of the neurons in the heart, revealing foundational insight into their role in heart attacks and other cardiac conditions.

Mapping the neurons of the rat heart in 3D
A team of researchers has developed a virtual 3D heart, digitally showcasing the heart's unique network of neurons for the first time.

How to put neurons into cages
Football-shaped microscale cages have been created using special laser technologies.

A molecule that directs neurons
A research team coordinated by the University of Trento studied a mass of brain cells, the habenula, linked to disorders like autism, schizophrenia and depression.

Read More: Neurons News and Neurons Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to