Researchers commonly use fear extinction as the main line of treatment for anxiety disorders. Extinction therapy aims to train the patient to distinguish non-threatening cues from threatening ones and to disassociate the threatening ones from fear memory. While this course of treatment has been shown to inhibit fear association, it does not erase its memory, and many patients return to a heightened state of fear in the long-term.
In new research, co-led by 2010 NARSAD Independent Investigator Grantee, Olivier J. Manzoni, Ph.D., of INSERM (Institut National de la Santé et de la Recherche Médicale) in France, an international team identified a receptor in the brain that may enable long term fear extinction. The researchers investigated the mechanisms underlying fear memory and its extinction by looking at fear conditioning in rats and mice. Specifically, they focused on the receptor proteins expressed on the surface of nerve cells in the brain called glutamate receptors that have been previously associated with fear learning and memory.
The team found that one such glutamate receptor, mGluR5, is important in inhibiting fear. Blocking mGluR5 with an inhibitor molecule impaired long-term fear extinction. On the other hand, when this receptor protein was not blocked, prolonged extinction training completely inhibited fear, possibly by degrading the original fear memory.
The findings, published online in the open-access resource of Public Library of Science, PloS One, offer a new target for anxiety treatments that may improve the effectiveness of fear extinction therapy by preventing the return of excessive fear during and after completion of therapy.
In addition to the implications for anxiety disorders, mGluR5 signalling has also been linked to Fragile X Syndrome, the most commonly known genetic cause of autism spectrum disorder. Genetic deletion of fragile X mental retardation protein (FMRP) is generally linked to the enhancement of mGluR5 signaling. In the fmr1-/- mice model of the disease, mice that do not express FMRP showed lower spontaneous recovery of fear after prolonged extinction training compared to normal mice. The data identify a previously undisclosed behavioral symptom of Fragile X Syndrome, further confirming the central role of mGluR5 in Fragile X.