On December 7th, I wrote a blog post about a published study in which scientists, Brian Dias and Kerry Ressler, demonstrated mice could transfer an experiential threat memory across three generations. As the spotlight shines heavy, debates among scientists heated up after it’s print debut in last week’s issue of Nature Neuroscience. The novel, comprehensive and meticulously produced findings wowed most researchers. Still, others criticized such a bold claim as being without an identified biological mechanism. Despite the skeptics, on January 10th, Ressler was excited and hopeful about the study’s implications at a talk in the NYU Langone Child Study Center.
To briefly recap, Dias and Ressler trained mice to associate the scent of acetophenone with a mild footshock by pairing the two through what’s known as Pavlovian conditioning. They mated these mice and found enhanced startle to this particular scent in “children” and “grandchildren.” Amazingly, having never experienced the smell, the animals were sensitive to it and larger brain areas devoted to acetophenone detection reflected this heightened awareness in all three generations. Dias and Ressler suspected an interaction between environment and changes in genetic activity, or epigenetics, was at work. They suggested chemical changes in sperm proteins carried a hidden memory, revealed only through discrete environmental cues.
The problem was that Dias and Ressler couldn’t pinpoint how information entered the sperm and altered activity of its DNA. They suggested DNA methylation, an epigenetic, chemical process that changes expression, not structure, of DNA. But other scientists challenged this proposition: it didn’t follow typical molecular behavior for the proteins examined.
Regardless, at his talk, Ressler revealed that they had replicated the results four times in the lab. The phenomenon was robust—did it matter the mechanism was a mystery? Yes, of course, but not quite yet. Science is an icy pond: to avoid sliding around and falling in, scientists take baby-steps. And this study is exactly that. Something in the sperm of these mice transmitted memories across generations, but Ressler admitted that without a mechanism, they cannot ask this question in humans.
Traditionally, a gap extends between basic and clinical research; however, Ressler (a neurobiologist and practicing psychiatrist) bridges this divide with a translational neuroscience approach. Complementing anecdotal evidence where humans inherit parental traumatic experience, this study offers an experimental animal model for something quite difficult to test in humans. While it’s nearly impossible to control a human’s environment and it takes years to track transgenerational changes, it’s “easy” in a rodent.
One thing was clear in his talk—Ressler knew a lot about childhood trauma and adult psychopathology. For example, Ressler identified biological predictors of Post Traumatic Stress Disorder risk and resiliency in women and has worked to find treatments to combat transgenerational anxiety. For now, he hopes to determine if he can reverse this inheritance in mice by “treating” parents’ trauma before they conceive. Somewhere down the line, knowing environmental triggers and how they function in the brain may reveal novel therapy methods that combine precise pharmacology. by: JoAnna Klein