Can Fear Memory Be Inherited?

Can the lasting effects of a parent’s stress or trauma be passed on to the next generation? A new study in mice suggests that, indeed, affective states may be passed on from generation to generation by way of epigenetic mechanisms. Of course, this claim has generated some strong discussion in the scientific community.

The authors first conditioned one generation of male mice to associate the smell of acetophenone with an aversive foot shock. Acetophenone activates a well-characterized receptor in olfactory neurons that is said to smell like cherries or almonds, and is normally non-noxious to mice. Following the aversive conditioning procedure, these mice demonstrated increased fear-potentiated startle (FPS) responses in the presence of acetophenone. FPS is an augmented startle response in the presence of an aversive conditioning cue. In this case, the presentation of acetophenone is the aversive cue.

Two weeks later, the mice were allowed to breed. Their first-generation offspring were tested at 2 months old for FPS in the presence of acetophenone odor, being themselves completely naïve to the smell. Compared with mice from unconditioned fathers, these mice did demonstrate increased FPS in the presence of acetophenone. Furthermore, FPS was also seen in the offspring of these mice, demonstrating measurable effects of the fear memory two generations past the original conditioning.

The authors also reported increased numbers of olfactory sensory neurons that express the acetophenone-specific receptor (M71 receptor, encoded by the Olfr151 gene) in offspring from the original fear-conditioned fathers. They claim that this inheritance is not by classical genetics, but rather by inherited alterations in epigenetic marks. Dias and Ressler call this an “under-appreciated influence on adult behavior – ancestral experience before conception.”

This work contributes to a growing group of studies giving evidence of epigenetic inheritance. One noteworthy example was published in 2002, demonstrating an increased risk of early death in grandchildren of farmers exposed to starvation conditions during puberty in Sweden (Bygren et al., 2001).

This work has generated a lot of buzz, and certainly not everyone is on board with epigenetic inheritance. What do you think?

Further Reading:

For more on epigenetic inheritance:

http://io9.com/how-an-1836-famine-altered-the-genes-of-children-born-d-1200001177

Bygren LO, Kaati G, Edvinsson S. Longevity determined by paternal ancestors’ nutrition during their slow growth period. (2001). Acta Biotheor. Mar;49(1):53-9.

Dias BG, Ressler KJ. Parental olfactory experience influences behavior and neural structure in subsequent generations. (2013). Nat Neurosci. Dec 1. doi: 10.1038/nn.3594. [Epub ahead of print]