New discovery shows where brain processes anxiety

Teresa Tanoos's picture
Area of the brain previously thought to reduce anxiety actually boosts it.
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If you struggle with feelings of anxiety, you can blame it on a portion of the brain that researchers recently discovered promotes anxiety.

The area of the brain related to anxiety was previously believed to reduce a person’s response to stress, but the researchers have since found the opposite occurs.

As reported in the journal Cell, the researchers found a brain circuit that connects the lateral septum (LS) with other areas of the brain in a manner that induces anxiety in response to stressful situations.

Study author David Anderson, of the Seymour Benzer Professor of Biology at California Institute of Technology, says that the study “identified a new neural circuit” that promotes states of anxiety. He explained that one reason there aren’t many effective anti-anxiety medications that work in all situations is because scientists have not yet uncovered exactly how the brain processes anxiety.

In this regard, this new study “opens up a new line of investigation into the brain circuitry” that controls anxiety in response to stress.

More than 18 percent of American adults suffer from anxiety disorders, according to the National Institutes of Mental Health. Symptoms of anxiety disorders include feeling overly worried, anxious and tense. When such feelings become excessive, they often manifest themselves physically, leading to body aches and pains, headaches and other symptoms of stress.

Other research studies on anxiety have focused mainly on the region of the brain called the amygdala, which processes anxiety. Because Prof. Anderson and his research team suspected that the LS could also have a connection to this process, either by promoting or inhibiting anxiety, they launched an experiment using mice in an effort to find answers.

The researchers set out to examine a circuit called the septohippocampal axis since other studies have found a link to it and anxiety. In such studies, which also used mice, the mice demonstrated anxious stress-induced behavior when brain cells in the LS were stimulated. The LS is located inside the circuit.

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However, when the LS was active during stress, did that mean it was promoting anxiety or limiting it?

Previously, scientists believed it was limiting stress, but with this study, the research team demonstrated that, in fact, it was actually promoting stress.

Using optogenetics, which is a technique that uses light to control the brain cells, the team stimulated an area of brain cells in the LS of mice, with the brain cells having a gene that was activated in response to light.

As a result, the mice exhibited obvious symptoms of anxiety, and additional tests showed that just a little stimulation of the LS induced anxious behavior in the mice that lasted at least 30 minutes.

The tests revealed that the specific brain cells that were activated in the LS of the mice were involved at the beginning of the anxious state, which persisted even after the cells were no longer stimulated.

So why did it take so long for researchers to figure out that these brain cells were not reducing anxiety as previously assumed?

Prof. Anderson says it’s because the LS promotes anxiety via a double-negative circuit, meaning neurons inhibit inhibitory neurons; thus, the neurons end up canceling out the inhibitory effect.

Indeed, that is what the researchers found, concluding that their test results confirm the double-negative notion.

The most surprising part of these findings, according to Prof. Anderson, is that they believed to dampen anxiety actually increased it instead – a finding he says is important for drug companies in order to develop better anti-anxiety drugs that do not target LS neurons since they’re now known to promote, not inhibit, states of anxiety.

SOURCE: Control of Stress-Induced Persistent Anxiety by an Extra-Amygdala Septohypothalamic Circuit, David J. Anderson, et al, Cell, DOI: 10.1016/j.cell.2013.12.040, published online 30 January 2014.

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