Memory for generations, at least in mice

Research: Mice leave memories to their offspring without changing DNA

All our traits are inherited from our parents, through the DNA we received from them. However, a new American study strengthens the hypothesis that there is also a parallel hereditary pathway. In this pathway the DNA does not change, but a substance that adheres to it affects gene expression. Such effects are called "epigenetic" - that is, "super-hereditary", and the researchers believe that they may be related to a long list of mental illnesses and other disorders in humans. Meanwhile, they proved the existence of such inheritance under certain conditions, in mice.

smell of pain

The researchers, from Emory University in Atlanta, gave mice mild electric shocks in their legs, and taught them to associate this pain with the smell of acetophenone, reminiscent of the scent of blossoming cherry or almond trees. After the link was made, the mice shrank in fear when exposed to the odor alone, even without the accompanying pain. The researchers discovered - to their surprise - that even in the next generation the mice reacted in a similar way to the smell of acetophenone, even though they were not familiar with it before, and even though the conditioning was created long before they were born. Even in the third generation, the response was preserved, and the grandchildren of the mice that passed the original conditioning still reacted with fear to the smell that their grandfathers had learned to associate with pain. The phenomenon existed both in mice that were born normally, and in those created by in vitro fertilization from the sperm of the males that underwent the conditioning, and the response was much stronger than in control mice, in which the conditioning did not occur. Other smells, apart from acetophenone, did not provoke any special reaction in the mice. Most of the experiments were done on males, although some experiments suggested that conditioning a female also passes the memory of fear on to her offspring.

Brain flexibility

In an attempt to decipher the mechanism that allows such inheritance, the researchers examined the brains of the mice. In an article in the journal Nature Neuroscience, they report that in the brains of the mice that underwent the conditioning, many more nerve cells were found that produce the acetophenone receptor. The structures that process the information from these nerve cells and transfer it to other areas of the brain were also larger than in mice from the control group (in which the conditioning did not occur) and their offspring. The researchers compared the DNA sequence of the gene responsible for the receptor that responds to the smell of acetophenone, but found no genetic difference between the conditioned mice and the control mice. Therefore, they believe that the differences lie in the degree of binding of methyl groups to the DNA of the mice. Methyl (CH3) is a substance that binds to DNA and affects gene expression. The ones who led the deciphering of this mechanism and its effect were the Israeli researchers Haim Sider and Aharon Razin, who in recent years have been mentioned as candidates for the Nobel Prize for these studies. The American researchers say that in the mice that became sensitive to the smell, there are fewer methylation sites in the DNA. In this case, the methyl paralyzes the expression of the gene, and if less methyl binds to the DNA, larger amounts of the receptor are produced, even during the development of the mouse. It affects the growth of brain cells, their connection to other cells and the development of the entire tissue.

Scientific controversies

The research findings arouse controversy among scientists, mainly because the researchers have not yet presented direct evidence for the correctness of the methylation hypothesis. According to them, such a revolutionary discovery in terms of our understanding of the mechanism of heredity, requires proof that leaves no room for doubt. In contrast, the supporters of the research state that these are convincing and comprehensive experiments, and the most accurate findings regarding epigenetic inheritance. Regarding the implications of the research, there are sharp disagreements among the scientists. Many researchers believe that this mechanism may provide an explanation for a family tendency to certain diseases, for which so far no genetic basis has been found. According to them, the findings may also explain the appearance of various diseases or deficiencies in children whose mothers were under mental stress during pregnancy, or in physical distress such as hunger. In contrast, the opponents claim that it is still too early to extrapolate from an experiment with mice and this method to what happens in humans in much more complex situations. In the end, we will surely prove which side is more right, but until then, everyone agrees that the findings are fascinating, and that more research is needed to explain them.

The research article in Nature Neuroscience