Heritability of Protective Conditioning

Sci Transl Med 26 February 2014: 
Vol. 6, Issue 225, p. 225ec37 
Sci. Transl. Med. DOI: 10.1126/scitranslmed.3008710


You Have Your Father’s Nose

  1. Vikaas S. Sohal

+Author Affiliations

  1. Department of Psychiatry and Center for Integrative Neuroscience, University of California, San Francisco, CA 94143, USA. E-mail: vikaas.sohal@ucsf.edu

Inheritance of vulnerability for neuropsychiatric disorders is multifactorial and is generally believed to occur via genetic and social mechanisms. However, recent discoveries about epigenetics have raised the possibility that after certain life experiences, epigenetic mechanisms may also transmit acquired vulnerabilities to subsequent generations. In a recent study, Dias and Ressler demonstrate that olfactory fear conditioning before conception in mice of the F0 generation leads to anatomical changes in the brain associated with an increased sensitivity to the conditioned odor in subsequent generations, along with epigenetic changes that could mediate these effects.

Dias and Ressler performed olfactory fear conditioning in F0 male mice before conception. Then, to measure the behavioral sensitivity of subsequent generations to the conditioned odors, they introduced these odors to naïve F1 or F2 mice during fear conditioning. F1 or F2 mice exhibited augmented startle responses in the presence of the odor to which their father or grandfather had been conditioned. Furthermore, the authors found an anatomical substrate that likely mediates this increased behavioral sensitivity. After odor fear conditioning, F0 mice exhibited an increase in the number of odorant receptors corresponding to the conditioned odor, and a resulting increase in physical size of the representation of this odor in the olfactory bulb. These same anatomical changes were present in F1 or F2 mice that had never been exposed to the conditioning odor. Furthermore, these effects were odor-specific; the increased behavioral sensitivity and anatomical changes only occurred for the conditioned odor, and not for other odors. Similar anatomical and behavioral changes also occurred in F1 mice conceived via in vitro fertilization and in mice that were cross-fostered after being born to mothers who underwent odor fear conditioning. The latter two observations suggest that these changes are transmitted via the germline rather than by social mechanisms. Indeed, the authors found specific reductions in the methylation of the gene encoding the odorant receptor for the conditioned odor in sperm from both F0 and F1 mice, demonstrating an epigenetic mechanism that could mediate the observed changes in odorant receptor number. The next steps will be to demonstrate that these epigenetic changes cause the observed anatomical and behavioral changes in F1 and F2 mice and to identify mechanisms that communicate olfactory experience to F0 sperm.

B. G. Dias, K. J. Ressler, Parental olfactory experience influences behavior and neural structure in subsequent generations. Nat. Neurosci. 17, 89–96 (2014). [PubMed]