If you or anyone you know have ever suffered from anxiety, you have probably wished there was some way you could turn it off, or at least turn down it’s volume. Brain researchers are looking for something similar as well.

Anxiety disorders include social phobias, post-traumatic stress disorder, and obsessive-compulsive disorder. They affect 40 million adult Americans in any given year, and the treatments currently available, like anti-anxiety drugs, are not always effective and may have unpleasant side effects.

“The targets that current anti-anxiety drugs are acting on are very nonspecific. We don’t actually know what the targets are for modulating anxiety-related behavior,” says Kay Tye, an assistant professor of brain and cognitive sciences at MIT.

Tye and her colleagues have revealed a communication path between two brain structures, the amygdala and the ventral hippocampus, which appears to control anxiety levels. By varying the volume of the communication path up and down in mice, the researchers found they could increase and decrease anxiety levels.

Close to the Edge

The hippocampus, necessary for memory formation, and the amygdala, which is involved in memory and emotion processing, have both been linked to anxiety. But how the two interact was unknown.

The researchers turned to optogenetics to examine those interactions. Optogenetics let them engineer neurons to turn their electrical activity on or off in response to light. Researchers customized a set of neurons in the basolateral amygdala (BLA); these neurons dispatch long messages to cells of the ventral hippocampus.

The mice anxiety levels were measured by how much time they were able to spend in a situation that usually makes them anxious. Mice are naturally anxious in open spaces where they are easy targets for predators, and when put in them, they tend to stay close to the edges.

When the connection between cells in the amygdala and the hippocampus were activated by researchers, the mice spent more time at the edges of an enclosure, suggesting they felt anxious. When the researchers shut off this pathway, the mice got more daring and willing to explore open spaces. On the other hand, when these mice had this pathway turned back on, they scuttled back to the sanctuary of the edges.

Multiple Redundancies

In a 2011 study, Tye showed that activating a different set of neurons in the amygdala had the reverse 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 totally opposite effects on anxiety,” Tye said. “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."

The latest study adds appreciably to neuroscientists' understanding of the roles of the amygdala and hippocampus in anxiety. It also points in new directions for drug targets, says Joshua Gordon, Columbia University associate psychiatry professor.

“The study specifies a particular connection in the brain as being important for anxiety. One could imagine, then, identifying components of the machinery of that connection – synaptic proteins or ion channels, for example – that are particularly important for amygdala-hippocampal connectivity. If such specific components could be identified, they would be potential targets for novel antianxiety drugs,” says Gordon.

Further studies are planned by the MIT team for investigating the effects of the amygdala on other targets in the hippocampus and the prefrontal cortex, which has also been implicated in anxiety. Decoding these circuits could be an big step toward finding better drugs to help treat anxiety.

Ada C. Felix-Ortiz, Anna Beyeler, Changwoo Seo, Christopher A. Leppla, Craig P. Wildes, Kay M. Tye. BLA to vHPC Inputs Modulate Anxiety-Related Behaviors. Neuron, 2013; 79 (4): 658 DOI:10.1016/j.neuron.2013.06.016

_ photo credit: Ada Felix-Ortiz Photo shows the tips of long neuronal extensions from the amygdala (blue) contact neurons of the hippocampus (green)._

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