In a nutshell: A newly identified brain circuit reignites the fear response, even after treatment to suppress it.

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Anxiety disorders, such as post-traumatic stress disorder, are often treated using exposure therapy, where the patient is repeatedly presented with the source or context of the anxiety, but in a safe environment where no harm ensues.

Unfortunately, even if patients learn to extinguish their fear during treatment, the fear response can re-emerge if they encounter the trigger outside the context of the clinic. Sometimes that fear is warranted – such as in dangerous situations – but other times, it is unnecessary and detrimental to their treatment. Understanding what causes fear relapse is therefore critical for developing effective therapy for trauma-related disorders.

Together with international collaborators, Brain Function CoE postdoctoral research fellow Roger Marek, chief investigator Pankaj Sah, and colleagues from the Queensland Brain Institute studied the brains of rats to see how fear relapse is controlled.

The researchers placed rats in a box with white lighting, and trained them to expect a mild electric shock after hearing a tone. When the rats were presented with the same tone after the initial training period, they displayed a fear response, even in the absence of the electric shock. After repeated exposure to the tone in the same box without receiving the subsequent shocks, their fear response was extinguished. However, when rats were placed in a different box – with fluorescent red lights – and presented with the same tone, the fear relapsed.

The team identified a previously unknown brain circuit in these rats that reignited the fear response: brain cells in the hippocampus – a brain region that is involved in memory storage – form connections with structures in the prefrontal cortex. This circuit enables the rats to express fear in the second box, where fear had not been previously extinguished. However, by artificially activating the circuit while rats were in the box where the fear had already been extinguished, the researchers reignited the rats’ fear.

The team’s discovery of this novel circuit presents a potential target for new treatments to reduce the possibility of fear relapse after therapy.

Next steps:
The researchers plan to investigate the precise sequence of events in these brain cells when fear is extinguished and when it relapses.


Marek, R., Jin, J., Goode, T. D., Giustino, T. F., Wang, Q., Acca, G. M., et al. (2018). Hippocampus-driven feed-forward inhibition of the prefrontal cortex mediates relapse of extinguished fear. Nature Neuroscience, doi: 10.1038/s41593-018-0073-9

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