Brain Cells Acting as 'Disappointment Meter' May Help Design New Class of Drugs, Study Finds

A study has found that a group of brain cells might act as a "disappointment meter", activating when reality falls short of expectations, and identifying these neurons could pave the way for a new and more effective class of medications for conditions like depression and addiction.

The findings, published in the journal Current Biology, reveal that the feeling of being let down is something that particular cells in the brain are designed to detect and record.

Mapping the cell types that show a sensitivity to disappointment might someday lead to a new class of medications that better treat neuropsychiatric disorders like depression and addiction, lead researcher and senior author Emily Sylwestrak, an assistant professor of biology in the University of Oregon College of Arts and Sciences, said.

Researchers looked at the lateral habenula region, a small, evolutionarily ancient structure located deep in the brain, and which processes negative emotions.

Previous studies have shown the region, sometimes referred to as the brain's 'anti-reward centre', to become active in response to unexpected negative events, such as a punishment out of the blue or a reward no longer granted.

However, the region contains many kinds of neurons, and scientists have yet to isolate the roles of individual cell types within it, the researchers said.

"What we're trying to understand is how those different cell types are mapped to particular behaviours. This new paper is a look at a cell type that we think is doing something very specific in the reward system," Sylwestrak said.

Sylwestrak and colleagues recorded brain activity in mice trained to poke their noses into a port to earn sugar water. After the mice had learned to expect a sweet sip when approaching the spot, the reward was sometimes smaller than expected or withheld entirely.

Comparing brain activity in worse-than-expected contexts, such as when the mice encountered a sudden puff of air, the researchers found that the neurons in question were relatively quiet, suggesting the cells may not be merely "bad news detectors".

The specificity is central for learning from mistakes, changing behaviours and perseverance, said author Kana Suzuki, a doctoral student in Sylwestrak's lab.

However, the cognitive processes can be disrupted in neuropsychiatric disorders.

"If you're looking at a neuropsychiatric disease, you need to know which knobs to turn to set things right," Sylwestrak said.

"So, if we know that a particular cell type is compromised in depression, for example, scientists might be able to design drugs that specifically target it and avoid the effects of stirring others," she said.