Reversing Behavioral, Neuroanatomical, and Germline Influences of Intergenerational Stress

Biological Psychiatry
Hadj S AouedBrian G Dias


Stressors affect populations exposed to them as well as offspring. Strategies preventing the intergenerational propagation of effects of stress would benefit public health. Olfactory cue-based fear conditioning provides a framework to address this issue. We 1) exposed adult male mice to an odor, acetophenone (Ace) or Lyral (parental generation [F0]-Exposed), 2) trained mice to associate these odors with mild foot shocks (F0-Trained), and 3) trained mice to associate these odors with mild foot shocks and then extinguished their fear toward these odors with odor-only presentations (F0-Extinguished). We then examined sensitivity of future generation (F1) offspring to these odors, expression of M71 odorant (Ace-responsive) and MOR23 odorant (Lyral-responsive) receptor-expressing cell populations in F1 offspring, and DNA methylation at genes encoding the Ace- (Olfr151, Olfr160) and Lyral- (Olfr16) responsive receptors in F0 sperm. Extinguishing fear toward Ace or Lyral of F0 male mice (F0-Extinguished) that had been fear conditioned with Ace or Lyral, respectively, results in F1-Extinguished offspring that do not demonstrate behavioral sensitivity to Ace or Lyral, respectively, and do not have enhanced representation for M71 or MOR2...Continue Reading


Nov 28, 2018·International Journal of Molecular Sciences·Jon G StellerApril E Ronca
Jan 17, 2020·Genes, Brain, and Behavior·Hadj S AouedBrian G Dias
Jun 7, 2020·Proceedings of the National Academy of Sciences of the United States of America·Rebecca K RehTakao K Hensch

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