What causes hallucinations: Mouse study uncovers unexpected changes in the brain’s signaling

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A study on mice found that the phenomena associated with these episodes may be the result of reduced signaling visual cortex


What causes hallucinations: Mouse study uncovers unexpected changes in the brain’s signaling that gives rise to visual phenomena

  • Researchers studied the brains’ of mice after gibing them a hallucinogenic drug
  • They found that brain signaling in the visual cortex appeared to decrease
  • The study suggest the phenomena also occur as a result of timing changes

Scientists may finally be close to understanding the mechanisms behind hallucination.

Despite the dramatic perceptual changes that take place during a bout of hallucination, what exactly happens in the brain during these moments has long been a mystery.

A new study on drugged mice has found that the phenomena associated with these episodes may be the result of reduced signaling in the visual cortex – not an increase, as was expected.

The images revealed that even after taking the drug, the signals being sent were largely similar to those seen in its absence, indicating that the information itself does not change. The neural responses are shown above

‘You might expect visual hallucinations would result from neurons in the brain firing like crazy, or by mismatched signals,’ says senior author Cris Niell, an associate professor and member of the Institute of Neuroscience at the University of Oregon.

‘We were surprised to find that a hallucinogenic drug instead led to a reduction of activity in the visual cortex.

‘In the context of visual processing, though, it made sense. 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 over-interpreting it, that could lead to hallucinations.’

In the study, mice were given a hallucinogenic drug called DOI (4-iodo-2,5-dimethoxyphenylisopropylamine), which is not regulated by the DEA, making it more accessible for research than other drugs such as LSD.

Similarly to others, though, it acts on serotonin 2A receptors.

The mice were then shown images on a screen, and researchers monitored the activity in their brains using calcium imaging and single-unit electrophysiology.

‘We’re interested in understanding how we create representations of the world using vision,’ Niell said.

A study on mice found that the phenomena associated with these episodes may be the result of reduced signaling visual cortex 

‘In many areas of biology, one of the best ways to study a process is to observe what happens when it’s perturbed.’

The images revealed that even after taking the drug, the signals being sent were largely similar to those seen in its absence.

According to the researchers, this means that the information itself does not change as a result of the drug, only its amplitude and timing.

The study suggests visual hallucinations may stem from reduced signaling in the visual cortex and altered timing of the neurons firing.

But, the researchers say, there’s still much more to be done.

‘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.’

HAVE SCIENTISTS UNRAVELED THE ‘RECIPE’ FOR ‘MAGIC SHROOMS’?

Research over the last few decades has suggested that the compound psilocybin may have a number of therapeutic benefits, with potential to help treat anxiety, depression, and even addiction.

But until now, the ‘recipe’ for psilocybin has remained a mystery.

In a new study, scientists have characterized the four enzymes mushrooms use to make this compound for the first time, setting the stage for pharmaceutical production of the ‘powerful psychedelic fungal drug.’

Scientists have characterized the four enzymes mushrooms use to make psilocybin

Scientists have characterized the four enzymes mushrooms use to make psilocybin

After identifying and characterizing the enzymes behind psilocybin, the team from Friedrich Schiller University Jena was able to develop the first enzymatic synthesis of the compound, reports C&EN, a publication from the American Chemical Society.

To get to the correct ‘recipe,’ the team in the new study sequenced the genomes of two mushroom species.

Then, they used engineered bacteria and fungi to confirm gene activity and the order of the synthetic steps, according to C&EN.

Their efforts revealed a new enzyme, dubbed PsiD strips carbon dioxide from the tryptophan, while another adds a hydroxyl group – or, oxygen and hydrogen.  

Another enzyme, known as PsiK acts as a catalyst for phosphotransfer.

Then, an enzyme known as PsiM catalyzes the transfer of methyl groups.

Based on their discovery, the researchers developed a ‘one-pot reaction’ to create psilocybin from 4-hydroxy-L-tryptophan, using three of the enzymes: PsiD, PsiK, and PsiM.

According to the team, the results could now ‘lay the foundation’ for the production of pharmaceutical drugs based on psychedelic mushrooms.

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