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January 20, 2015

Old Memories Can Learn New Tricks

  • Two independent research teams have identified the underlying mechanisms in the fear memory circuit for mice and rats. Research that could provide crucial insight for individuals suffering from anxiety disorders such as post-traumatic stress disorder (PTSD).

    The results from both studies (“A temporal shift in the circuits mediating retrieval of fear memory” and “The paraventricular thalamus controls a central amygdala fear circuit”) were published in Nature.

    In the first study, a research team led by Gregory Quirk, Ph.D., from the University of Puerto Rico School of Medicine, conditioned rats to fear by associating a specific tone with a mild shock. Although the rats’ outward behavior remained unchanged over time, the neural pathway charged with remembering the traumatic event took a divergent route.

    "While our memories feel constant across time, the neural pathways supporting them actually change with time," clarified Dr. Quirk "Uncovering new pathways for old memories could change scientists' view of post-traumatic stress disorder, in which fearful events occur months or years prior to the onset of symptoms."

    Dr. Quirk and his team found that the fear conditioning initially created a circuit running from the prefrontal cortex, the executive branch of the brain, to the amygdala, the fear center. Interestingly, the researchers observed that several days later the fear memory recall had detoured from the prefrontal cortex to an area within the thalamus called the paraventricular region (PVT). The PVT then connects with a different part of the amygdala, which mediates fear learning.

    The investigators surmised that the PVT may function to consolidate fear with stress, thus strengthening the fear memory.

    "In people with anxiety disorders, any disruption of timing-dependent regulation in retrieval circuits might worsen fear responses occurring long after a traumatic event," Dr. Quirk postulated.

    In the second study, scientists from Cold Spring Harbor Laboratory looked at the molecular mechanisms essential to the long-term fear circuit within mice and how they translate the stress detection into an adaptive behavior.

    Bo Li, Ph.D. principal investigator on this study, and her colleagues discovered the same shift in the fear memory retrieval pathway in mice that Dr. Quirk’s team had in rats. Dr. Li’s team was able to isolate a specific protein that was responsible for activating specific neurons in the central amygdala, brain-derived neurotrophic factor (BDNF).  Furthermore, when the team infused BDNF into the central amygdala area of mice they were able to cause them to freeze in fear, implying that this protein mediates fear memories as well as fear responses.

    BDNF has been previously linked to mood and anxiety disorders, such as PTSD, and is a possible target for pharmacological intervention.
     

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