Neurology Central

Could targeting ‘extinction neurons’ help treat anxiety and PTSD?

Neuroscientists from the University of Texas at Austin (TX, USA) have identified a population of cells in the brain that are involved in the reoccurrence of fear memories. The study, published in Nature Neuroscience, may improve our understanding of conditions such as anxiety and post-traumatic stress disorder (PTSD).

Spontaneous recovery of fear memories can occur at any time and can cause much distress for people living with fear-based disorders such as anxiety, phobias and PTSD. “There is frequently a relapse of the original fear, but we know very little about the mechanisms,” commented Michael Drew (University of Texas at Austin).

During exposure therapy, the recommended treatment for fear-based disorders, memories of safety known as “extinction memories” override the original fear memory. “Extinction does not erase the original fear memory but instead creates a new memory that inhibits or competes with the original fear,” explained Drew.

The study has identified “extinction neurons” in the brain which, when activated, suppress fear memories. When activation stops, the fear memories can return. “Our paper demonstrates that the hippocampus generates memory traces of both fear and extinction, and competition between these hippocampal traces determines whether fear is expressed or suppressed,” continued Drew.

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To understand how the extinction neurons work, the researchers studied mice. The animals were placed in a distinctive box and were given a harmless shock to induce fear. Following this, when the mice were placed in the box, they would exhibit fear behavior. Mice were then promoted to form extinction memories by being placed in the box without a shock.

The technique of optogenetics was then utilized to activate the extinction neurons of mice. “Artificially suppressing these so-called extinction neurons causes fear to relapse, whereas stimulating them prevents fear relapse,” stated Drew.

Exposure therapy is not always effective, and further investigation into the role of extinction neurons may enable neuroscientists to improve the therapy. They may also be able to explore new avenues of drug development.

“These experiments reveal potential avenues for suppressing maladaptive fear and preventing relapse,” concluded Drew. “They can help us understand the potential cause of disorders, like anxiety and PTSD, and they can also help us understand potential treatments.”

Sources: Lacagnina AF, Brockway ET, Crovetti CR et al. Distinct hippocampal engrams control extinction and relapse of fear memory. Nat. Neurosci. doi:10.1038/s41593-019-0361-z (2019) (Epub ahead of print);