Wednesday, December 4, 2013

Parental olfactory experience influences behavior and neural structure in subsequent generations

Dias, B.G., Ressler, K.J. (2013). Parental olfactory experience influences behavior and neural structure in subsequent generations. Nature Neuroscience.

The phenomenon of "inheritance of parental traumatic exposure".

We've long recognized that the ability to transmit information to offspring about specific environmental features or events would be remarkably advantageous. However, we've only been able to conceive of such "non-Mendelian" modes of inheritance only recently. Since Darwin, we have suspected that the information shared across generations was only crafted by natural selection and that traits were determined by who best reproduced and not through the experiences of the orgnaisms. But new empirical data is showing that epigentics can act as the mechanism to pass down information learned from the environment to the next generation.

A standard behavioral test is called Fear conditioning -- an animal is taught to associate an arbitrary stimulus was some kind of painful shock. Animals learn these associations very quickly, and we can measure an animal's startle response to the arbitrary stimulus as an indicator of how well an animal learned to associate the stimulus with the shock.

Three generation of mice were studied -- F0 were the grandparents and put in 3 conditions: no smells, exposed to acetophenone (smells like cherries), and exposed to propanol (control smell). The offspring of F0 (F1) were then tested to see if they responded to the smell that their parents were conditioned to. The mice responded more to the odor that their parents were conditioned to, but not the other odor, even though these mice were never exposed to either odors. This even extended to the next generation (F2).

Further, F1 mice showed higher sensitivity to the smell that their parents were conditioned with.

Cross-fostering experiments indicated that the behavioral changes were not passed down from social learning and indicated that the enhanced sensitivity and behavioral changes were genetic.

The glomeruli (packet of neurons that respond to specific smells) that respond to acetophenone showed anatomical differences when the parents were conditioned to acetophenone.

Figure 4 Behavioral sensitivity and neuroanatomical changes are inherited in F2 and IVF-derived generations. (a,b) Responses of F2-C57Bl/6J males revealed that F2-Ace-C57 mice had an enhanced sensitivity to acetophenone compared with F2-Prop-C57 mice (a). In contrast, F2-Prop-C57 mice had an enhanced sensitivity to propanol compared with F2-Ace-C57 mice (b; F2-Prop-C57, n = 8; F2-Ace-C57, n = 12; OPS to acetophenone: t test, P = 0.0158, t18 = 2.664; OPS to propanol: t test, P = 0.0343, t17 = 2.302). (c–f). F2-Ace-M71 mice whose F0 generation male had been conditioned to acetophenone had larger dorsal and medial M71 glomeruli in the olfactory bulb than F2-Prop-M71 mice whose F0 generation had been conditioned to propanol. Scale bar represents 200 ┬Ám. (g) Dorsal M71 glomerular area in F2 generation (M71-LacZ: F2-Prop, n = 7; F2-Ace, n = 8; t test, P < 0.0001, t13 = 5.926). (h) Medial M71 glomerular area in F2 generation (M71-LacZ: F2-Prop, n = 6; F2-Ace, n = 10; t test, P = 0.0006, t14 = 4.44). (i) Dorsal M71 glomerular area in IVF offspring (F1-Prop-IVF, n = 23; F1-Ace-IVF, n = 16; t test, P < 0.001, t37 = 4.083). (j) Medial M71 glomerular area in IVF offspring (F1-Prop-IVF, n = 16; F1-Ace-IVF, n = 19; t test, P < 0.001, t33 = 5.880). Data are presented as mean ± s.e.m.*P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.

Finally, they looked at the methylation patterns on the odorant receptor genes in the sperm of the F0 mice. Methylation has been recognized as a potential marker for epi-genetic changes in transcription. There was a significant decrease in the amount of methylation of Olfr151 (which is responsive to acetophone), but no changes in Olfr6 (which is not responsive).

The idea that the experience of ones ancestors can influence behavior has important consequences. This may contribute to an "intergenerational transmission of risk for neurophsychiatric disorders, such as phobias, anxiety and post-traumatic stress disorder".

The fact that changes can propagate over more than one generation has implications for the process of evolution -- the actual experience of the parents altering the genetic makeup of the offspring means we may have to refine the way we think about how evolution works. However, it is unclear if these changes can last for a long enough time (over many generations) to truly alter evolution, as methylation patterns may not be stable enough for natural selection to have a long-term influence. But there could be mechanisms that can incorporate epi-genetic changes into the genome.