This phenomenon—“transgenerational epigenetic inheritance”—was demonstrated recently in a study published in Nature Neuroscience about the inheritance of certain smell memories in mice, which were passed down through at least two generations.
In the study, mice were trained to be afraid of acetophenone, a fruity smell that’s used in cherry, jasmine, honey-suckle and almond flavorings. The researchers paired this fragrance with a foot shock so that it soon became a warning signal to the mice, instilling fear and alerting them to an impending attack. The mice’s noses and brains also adapted accordingly, generating additional M71 neurons—cells receptive to this particular scent—so that they would be extra sensitive to the smell. So far, this is all basic Pavlovian conditioning and neural adaptation, nothing special yet.
However, the crazy part is that the offspring of these mice, who had never before been exposed to that smell, also showed increased fear and startle responses to the scent. This suggests that the learned association, connecting the smell with danger, was passed down from one generation to the next. And this second group’s offspring also showed heightened sensitivity to the odor. Thus, three generations of mice were affected by the conditioning, even though only one of them had actually experienced it. Behind these behavioral effects were similar changes in the noses of each of these offspring groups, with larger M71 receptors present and an increase in the number of M71 neurons available.
Importantly, these results did not stem from any socially learned behaviors picked up by hanging around the anxious parent. The mice showed no reaction to other smells and had no fear responses to sounds or different types of warnings. To confirm this, the scientists even took sperm from the first set of mice, used IVF to implant them in females from another lab, raised them in isolation away from any untoward influences, and still found an increased sensitivity to the original scent.
But how exactly does this happen?
In an attempt to explain this phenomenon, the scientists turned to the first animals’ genotype to try and figure out what exactly was behind this inherited learning. It turns out that the genes involved in the expression of M71 receptors were less inhibited in these animals, meaning that they were more “turned on,” possibly resulting in a greater proliferation of the neurons. This same effect was found in the mice’s sperm, meaning that this trait would be passed down through to the next generation, potentially resulting in an inherited sensitivity to that same fruity scent.
While some have questioned epigenetics’ role in inherited learning, this is not the only example of this type of phenomenon.
Two studies presented at the Society for Neuroscience conference in November describe a similar inherited sensitivity to alcohol and cocaine in the offspring of drug and alcohol-dependent rats. Surprisingly, these rats were actually less responsive to the drugs than control animals and were less likely to self-administer the substances. This flies in the face of prior addiction research, where the children of dependent drug users were thought to have a greater risk of becoming addicted themselves. Inherited changes in neurons in the nucleus accumbens—a primary reward center in the brain—may be behind this effect in the young rats, dulling the typically rewarding effects drugs have due to inherited biological changes from their addicted parents.