Brain Facts

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Neural circuit that directly influences anxiety

Researchers have revealed a major breakthrough in treating anxiety disorders.

A California team has discovered the region of the brain that controls how anxious we are - and found it wasn't where they had thought.

The team now say it could now be targeted with drugs, leading to far more effective treatments within a decade.

Previous studies of anxiety in the brain have focused on the amygdala, an area known to play a role in fear. However, a team of researchers led by biologists at the California Institute of Technology (Caltech) had a hunch that understanding a different brain area, the lateral septum (LS), could provide more clues into how the brain processes anxiety.

Their instincts paid off?using mouse models, the team has found a neural circuit that connects the LS with other brain structures in a manner that directly influences anxiety.

'Our study has identified a new neural circuit that plays a causal role in promoting anxiety states,' says David Anderson of Caltech, who led the study.

'Part of the reason we lack more effective and specific drugs for anxiety is that we don't know enough about how the brain processes anxiety.

'This study opens up a new line of investigation into the brain circuitry that controls anxiety.'

The team's findings in the January 30 version of the journal Cell.

In the new study, the team used optogenetics?a technique that uses light to control neural activity?to artificially activate a set of specific, genetically identified neurons in the LS of mice.

During this activation, the mice became more anxious.

The researchers also found that even a brief, transient activation of those neurons could produce a state of anxiety lasting for at least half an hour.

This indicated that not only are these cells involved in the initial activation of an anxious state, but also that an anxious state persists even after the neurons are no longer being activated.

'The most surprising part of these findings is that the outputs from the LS, which were believed primarily to act as a brake on anxiety, actually increase anxiety, say the researchers.

Knowing the sign?positive or negative?of the effect of these cells on anxiety is a critical first step to understanding what kind of drug one might want to develop to manipulate these cells or their molecular constituents.

If the cells had been found to inhibit anxiety, as originally thought, then one would want to find drugs that activate these LS neurons, to reduce anxiety.

However, since the group found that these neurons instead promote anxiety, then to reduce anxiety a drug would have to inhibit these neurons.

'We are still probably a decade away from translating this very basic research into any kind of therapy for humans, but we hope that the information that this type of study yields about the brain will put the field and medicine in a much better position to develop new, rational therapies for psychiatric disorders,' said Anderson.

'There have been very few new psychiatric drugs developed in the last 40 to 50 years, and that's because we know so little about the brain circuitry that controls the emotions that go wrong in a psychiatric disorder like depression or anxiety.'

The team will continue to map out this area of the brain in greater detail to understand more about its role in controlling stress-induced anxiety.

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