Optogenetics helps uncover the mechanism by which fear is learned

A team of researchers at the Universitat Autònoma de Barcelona (UAB; Spain) and Harvard University (Cambridge, MA) used optogenetics to laser-stimulate Tac2 neurons in the cerebral amygdala, which play a key role in the memory of fear. By doing so, treated mice increased their long-term memory and helped the researchers to understand the mechanism by which fear is learned, so the work is promising for treating disorders related to fear, including phobias, obsessive-compulsive disorder, and post-traumatic stress disorder.

Related: Optogenetics helps understand what causes anxiety and depression

Tac2 neurons need to be previously made sensitive to light by introducing a virus in a specific cerebral area. There, the neurons are necessary to store memories related to fear. The mice in the research team's study that received this treatment saw their long-term memory increased and, therefore, were better at remembering danger.

"Our discovery stresses the importance of Tac2 neurons in the regulation of fear, and opens the door to new therapeutical targets for the treatment of diseases related to fear such as phobias, obsessive-compulsive disorder, and post-traumatic stress disorder," explains Raül Andero Galí, one of the heads of the Neurobiology of Stress and Addiction research group at the Institut de Neurociències (INc) of UAB and a researcher at Harvard University. "Moreover, it can also help to find new ways to improve the memory of healthy people or people with memory problems," he adds.

Microphotography of the cerebral amygdala. Tac2 neurons, involved in the memory of fear, are marked in green, with the nucleus of amygdala neurons in blue.

To reach these conclusions, researchers observed the behavior of two mice populations: one under optogenetics treatment and the other under no treatment. They both were exposed to a tone and then received an unpleasant electrical stimuli. Mice stimulated by optogenetics remembered that the tone preceded the stimuli longer and showed more signs of fear when they heard the tone days later.

In 2014, Kerry Ressler (McLean Hospital at Harvard University) and Andero patented a drug that modulates this type of memory. The drug, and other analogs, may be capable of decreasing the emotional consequences a traumatic event can cause in the future and minimize the risk of suffering mental disorders related to the trauma.

In future studies, Andero and his collaborators will continue to study the cerebral mechanisms by which fear is learned, including how the amygdala communicates with other parts of the brain also related to fear learning.

Full details of the work appear in the journal Neuropsychopharmacology; for more information, please visit http://dx.doi.org/10.1038/npp.2016.77.

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