Inheriting Life Experiences

The nature versus nurture debate has long been dead and buried. From the ashes arose a new preposition:  nature with nurture. While it is true that genes, the functional unit of DNA, are hereditary, what happens to those genes depends on environmental factors. Certain environments and experiences affect what happens to a gene and thereby the protein product of the gene.
This variation in what happens to otherwise predetermined DNA is called epigenetics: the study of changes in gene expression without actually altering the genes. Chemical flags can be attached to portions of DNA that promote or inhibit that area from expression, fine-tuning the inflexible DNA to adjust the presence of proteins to meet situational needs. One’s experiences don’t rewrite the genetic code but they can tweak it. Epigenetics is the “with” in “nature with nurture.” And while it is relatively agreed that these changes to one’s genome are heritable — dubbed transgenerational epigenetic inheritance –a new study in Nature Neuroscience has revealed some light on how.
Dr. Dias and Dr. Ressler at Emory University conditioned a group of mice to fear a fruity odor, called acetophenone, by pairing it with a mild foot shock. After making the association between the painful shock and acetophenone, these mice would have an increased startle response when acetophenone was presented. This is nothing new; simple Pavlovian conditioning.  Previous studies had shown that this change in startle response was a reflection of an increase of neurons in the animal’s nose sensitive to that particular scent (M79 neurons).
Ten days after this training, the (male) mice were allowed to breed. After these baby mice were born and matured, they were exposed to acetophenone, just like their fathers. These offspring had never been exposed to the scent before, let alone shocked while smelling it, so they had no reason to fear it. Yet the children of those trained to fear the fruity odor also showed the same fear, just as if they had been shocked. And, even more impressively, the children of those children – the grandchildren – also had increased startle reactions.
"Thanks a lot, Grandpa"

“Thanks a lot, Grandpa”

When researchers examined the brains of the children and grandchildren mice, they found similarly changed neural architecture:  an increase in neurons sensitive to that specific smell as well as a larger group of neurons reporting that smell to the brain.
But, what if that startle response where somehow learned and not the result of genetics? Perhaps the fathers somehow taught the offspring to be sensitive to particular odors. To account for this, researchers also extracted sperm from the trained mice, and using in vitro fertilization, impregnated mice on the other side of campus where any social learning of such fear behavior would be impossible. Astonishingly, these in vitro babies had the same increase in startle response and mediating neurons than the natural children did.
Altogether, this means that a life experience, which in this case is a mild electric shock paired with a fruity smell, caused a biochemical cascade to flag the neurons responding to that smell for increased production, and that change in the brain’s cells somehow made it down to the testes where sperm were produced reflecting this change, passing along this predisposition to children, who incorporated it into all the cells in their entire body, who then passed it along to the grandchildren!
[as a side note, now would be a good time to read up on Lamarck: a French naturalist, rival of Darwin, and originator of the idea that life experiences are inheritable]
I'm back, baby!

I’m back, baby!

What this study did not show is that all life experiences are heritable. In this particular instance, where a behavior was largely controlled by a relatively simple smell pathway, there is clear evidence that the children were genetically wired to fear this smell from the parent’s experience. But that is a long ways away from demonstrating that all experiences, particularly more complex ones, can be transmitted in a similar fashion. With that caveat, this has remarkable implications for important clinical insights, particularly in cases of PTSD, abuse, and stress, opening an avenue for new research into why certain predispositions travel through generations. The Ressler lab is currently looking at whether unlearning the association between the fruity smell and the shock will revert the genomic changes that influenced two generations of mice – the findings of which could greatly inform how we help those who have experienced traumatic life events.
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