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Brain Circuit Activity Can Change Anxiety Levels

By: Sai Srihaas Potu

Over the last two decades, brain imaging studies have helped researchers better understand the neural circuitry of anxiety and related disorders, particularly regions involved in fear processing and obsessive-compulsive symptoms. The neural circuitry of fear processing involves the amygdala, anterior cingulate, and insular cortex, while cortico-striatal-thalamic circuitry plays a key role in obsessive-compulsive disorder.

Basic and clinical studies have led to advances in our understanding of the neural circuitry of anxiety and related disorders. With increasing numbers of older adults in the general population, anxiety will become a widespread problem in late life and one of the major causes of health care access contributing to high societal and individual costs. Unfortunately, the detection of anxiety disorders in late life is complicated by a series of factors that make it different from assessment in younger cohorts, such as differential symptom presentation, high comorbidity with medical and mental disorders, the aging process, and newly emergent changes in life circumstances.

Late-life anxiety is a highly prevalent psychiatric condition. Prevalence rates of anxiety disorders among older adults are 1.2%–15% in community samples and 1%–28% in clinical samples of older adults. Evaluating the clinical expression and intensity of anxiety in older adults represents a significant change in research.

Anxiety disorders, which include post-traumatic stress disorder, social phobias, and obsessive-compulsive disorder, affect 40 million American adults in a given year. Currently available treatments, such as anti-anxiety drugs, are not always effective and have unwanted side effects.

To develop better treatments, a more specific understanding of the brain circuits that produce anxiety is necessary, says Kay Tye, an assistant professor of brain and cognitive sciences and a member of MIT’s Picower Institute for Learning and Memory.

Currently, targets that antianxiety drugs are acting on are very nonspecific. With no reliable treatment options, many people continue to suffer from anti-anxiety disorders.

In a step toward uncovering better targets, Tye and her colleagues have discovered a communication pathway between two brain structures — the amygdala and the ventral hippocampus — that appears to control anxiety levels. By turning the volume of this communication up and down in mice, the researchers were able to boost and reduce anxiety levels.

Both the hippocampus, which is necessary for memory formation, and the amygdala, which is involved in memory and emotion processing, have previously been implicated in anxiety. However, it was unknown how the two interact.

To study those interactions, the researchers turned to optogenetics, which allows them to engineer neurons to turn their electrical activity on or off in response to light. For this study, the researchers modified a set of neurons in the basolateral amygdala (BLA). BLA neurons send long projections to cells of the ventral hippocampus.

The researchers tested the mice’s anxiety levels by measuring how much time they were willing to spend in a situation that normally makes them anxious. Mice are naturally anxious in open spaces where they are easy targets for predators, so when placed in such an area, they tend to stay near the edges.

When the researchers activated the connection between cells in the amygdala and the hippocampus, the mice spent more time at the edges of an enclosure, suggesting that they felt anxious. When the researchers shut off this pathway, the mice became more adventurous and willing to explore open spaces. However, when the mice had this pathway turned back on, they scampered back to the security of the edges.

In a previous study, Tye found that activating a different subset of neurons in the amygdala had the opposite effect on anxiety as the neurons studied in the new paper, suggesting that anxiety can be modulated by many different converging inputs.

“Neurons that look virtually indistinguishable from each other in a single region can project to different regions and these different projections can have opposite effects on anxiety,” Tye says. “Anxiety is such an important trait for survival, so it makes sense that you want some redundancy in the system. You want a couple of different avenues to modulate anxiety.”

This study contributes significantly to scientists’ understanding of the roles of the amygdala and hippocampus in anxiety and offers directions for seeking new drug targets. The study specifies a particular connection in the brain as being important for anxiety. This will allow researchers to properly identify components of the machinery of that connection — synaptic proteins or ion channels. If such specific components could be identified, they would be potential targets for novel antianxiety drugs.

In future studies, the MIT team plans to investigate the effects of the amygdala on other targets in the hippocampus and the prefrontal cortex, which has also been implicated in anxiety. Deciphering these circuits could be an important step toward finding better drugs to help treat anxiety.

Social anxiety is a prevalent psychiatric problem in our society. Many people avoid social situations, fearing they may be humiliated or embarrassed. Social anxiety can have multiple causes. It usually forms in childhood but may not be fully apparent until young adulthood. A negative style of parenting can foster the appearance of social anxiety, as children learn that the opinions of others are very important and strongly influence self-worth.

While there has been progress in the knowledge of how psychotherapy impacts neural function, particularly in networks about cognitive regulation of emotion, there is still wide heterogeneity in fMRI studies, which prevents the drawing of firm conclusions. The study conducted by Professor Tye may help neuroscientists pinpoint better targets for anti-anxiety treatments which can help save many lives.


1. Ayers CR, Sorrell JT, Thorp SR, Wetherell JL. Evidence-based psychological treatments for late-life anxiety. Psychology and Aging. 2007.

2. Beekman AT, De Beurs E, Van Balkom AJ, Deeg DJ, Van Dyck R, Van Tilburg W. Anxiety and depression in later life: co-occurrence and communality of risk factors. American Journal of Psychiatry. 2000.

3. Kay M. Tye, Rohit Prakash, Sung-Yon Kim, Lief E. Fenno, Logan Grosenick, Hosniya Zarabi. Amygdala circuitry mediating reversible and bidirectional control of anxiety. Nature. 2011.

4. Kogan JN, Edelstein BA, McKee DR. Assessment of anxiety in older adults: current status. Journal of Anxiety Disorders. 2000.


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