Safety Learning (Pollak et al)

   In my previous entry, I talked about an article written by an astonishing researcher in the field of neural circuit mechanisms found in major depressive disorder. Allyson Friedman, Ph.D., mentioned seeking novel targets for treating depression and developing a more natural acting antidepressant with little side effects and better results.

   In the Pollak et al paper, researchers were able to show how learned safety, as an animal model, can reduce depression-like behavior in mice and through different molecular pathways bring forth some effects of pharmacological antidepressants. Also, learned safety was able to promote the survival of newborn cells in the hippocampus, to be more specific in the dentate gyrus. Based on other publications, the hippocampal volume is smaller in depressed patients, and its small size has been thought to be due to fewer granule neurons in the dentate gyrus.

   Antidepressants are though to reverse the decrease of granule neurons in the dentate gyrus by increasing the expression of brain-derived neurotropic factor. An increase in BDNF was found in safety conditioned mice in the Pollak et al paper. BDNF also plays an important role in learning, long term memory and neurogenesis. If an animal model of learned safety could help bring forth such changes in the hippocampus of mice, could it be crucial to the advancement of research in human depression?

   A year ago a research article was published where a group of researchers from the University of California San Diego and veterans affiliated organizations in the San Diego area investigated the effects of fear conditioning and safety learning on REM sleep in healthy adults.¹ Even though the shock delivered to humans was not as strong or closely aversive as the one delivered to animals in animal studies, the researchers were wondering on whether someone will explore the relationship between safety learning and sleep in animals. After all, disturbances in sleep is often a symptom of depression. By the way, the study was looking into the role of sleep in post-traumatic stress disorder.

   Their findings suggest that safety signal learning was related to increased REM sleep in subjects and proposed that safety learning that would lead to an increase in REM sleep may increase neurogenesis and promote cell proliferation and survival. Coincidentally, the findings in Pollak et al paper did find suggest the increase of neurogenesis and cell proliferation as well.

   Even though at the beginning I was skeptical of Pollak and her team’s study, it turned out to be quite a revelation. It would have been wonderful if Pollak and her team had explored the sleeping pattern of mice, social interaction after being fear conditioned or safety conditioned, or even changes in their appetite would have been a great addition to their findings. I think they should of focused on symptoms of sadness and anhedonia rather than focusing on stress and fear. Since feelings of stress and fear would make a better focus for a study about Generalized Anxiety Disorder and post-traumatic stress disorder than it would for depression.

Reference:

       1. Sean P.A. Drummon, PhD. Anisa J. Marshall. Dean T. Acheson. Victoria B. Risbrough. “Fear Conditioning, Safety Learning, and Sleep in Humans” Journal of Neuroscience, 27 August 2014. http://www.jneurosci.org/content/34/35/11754.full

P.S. Take a look of this video, notice how the mouse would freeze upon hearing the tone. Even though it is a bit different from what Pollak and her team did, it does help visualize part of their experiments  https://www.youtube.com/watch?v=ZlZekx1P1g4