Breakthrough for new stress and anxiety treatments

By Stephen Beech via SWNS

New treatments for stress and anxiety may be possible after scientists worked out how the brain assigns positive or negative emotions to memories.

It may sound like the realms of science fiction, but an American research team has discovered a molecule in the brain responsible for associating good or bad feelings with a memory.

They say their findings, published in the journal Nature, pave the way for a better understanding of why some people are more likely to retain negative emotions than positive ones - as can happen with anxiety, depression or post-traumatic stress disorder (PTSD).

Senior author Professor Kay Tye, of the Salk Institute's Systems Neurobiology Laboratory, said: “We’ve basically gotten a handle on the fundamental biological process of how you can remember if something is good or bad.

“This is something that’s core to our experience of life, and the notion that it can boil down to a single molecule is incredibly exciting.”

She explained that for a human or animal to learn whether to avoid, or seek out, a particular experience again in the future, their brain must associate a positive or negative feeling - or “valence” - with that stimulus.

The brain’s ability to link these feelings with memories is called “valence assignment.”

In 2016, Prof Tye discovered that a group of neurons in the brain’s basolateral amygdala (BLA) helps assign valence when mice are learning.

One set of BLA neurons was activated with positive valence, as the animals learned to associate a tone with a sweet taste.

A separate set of BLA neurons was activated with negative valence, as the animals learned to associate a different tone with a bitter taste.

Prof Tye said: “We found these two pathways - analogous to railroad tracks - that were leading to positive and negative valence, but we still didn’t know what signal was acting as the switch operator to direct which track should be used at any given time."

In the latest study, Prof Tye's team homed in on the importance of the signaling molecule neurotensin to the BLA neurons.

They already knew that neurotensin is a neuropeptide produced by the cells associated with valence processing, but so are a few other neurotransmitters.

The team used CRISPR gene editing approaches to selectively remove the gene for neurotensin from the cells - the first time that CRISPR has been used to isolate specific neurotransmitter function.

Without neurotensin signaling in the BLA, Prof Tye explained that mice could no longer assign positive valence and didn’t learn to associate the first tone with a positive stimulus.

She said: "Interestingly, the absence of neurotensin did not block negative valence.

"The animals instead became even better at negative valence, having a stronger association between the second tone and a negative stimulus.

"The findings suggest that the brain’s default state is to have a bias toward fear - the neurons associated with negative valence are activated until neurotensin is released, switching on the neurons associated with positive valence."

From an evolutionary perspective, Prof Tye says it "makes sense" because it helps people avoid potentially dangerous situations -and it probably resonates with people who tend to find the worst in a situation.

In further experiments, Prof Tye and her team showed that high levels of neurotensin promoted reward learning and dampened negative valence, further supporting the idea that neurotensin is responsible for positive valence.

Co-first author Hao Li, a postdoctoral fellow in the Tye Lab, added: “We can actually manipulate this switch to turn on positive or negative learning.

“Ultimately, we’d like to try to identify novel therapeutic targets for this pathway.”

The researchers still have questions about whether levels of neurotensin can be modulated in people’s brains to treat anxiety or PTSD.

They are also planning future studies to probe what other brain pathways and molecules are responsible for triggering the release of neurotensin.