Proximate causes and consequences of intergenerational influences of salient sensory experience

Abstract

Salient sensory environments experienced by a parental generation can exert intergenerational influences on offspring. While these data provide an exciting new perspective on biological inheritance, questions remain about causes and consequences of intergenerational influences of salient sensory experience. We previously showed that exposing male mice to a salient olfactory experience, like olfactory fear conditioning, resulted in offspring demonstrating a sensitivity to the odor used to condition the paternal generation and possessing enhanced neuroanatomical representation for that odor. In this study, we first injected RNA extracted from sperm of male mice that underwent olfactory fear conditioning into naïve single‐cell zygotes and found that adults that developed from these embryos had increased sensitivity and enhanced neuroanatomical representation for the odor (Odor A) with which the paternal male had been conditioned. Next, we found that female, but not male offspring sired by males conditioned with Odor A show enhanced consolidation of a weak single‐trial Odor A + shock fear conditioning protocol. Our data provide evidence that RNA found in the paternal germline after exposure to salient sensory experiences can contribute to intergenerational influences of such experiences, and that such intergenerational influences confer an element of adaptation to the offspring. In so doing, our study of intergenerational influences of parental sensory experience adds to existing literature on intergenerational influences of parental exposures to stress and dietary manipulations and suggests that some causes (sperm RNA) and consequences (behavioral flexibility) of intergenerational influences of parental experiences may be conserved across a variety of parental experiences.

Paternal adverse childhood experiences: Associations with infant DNA methylation

“…Additionally, animal work has elucidated paternal effects of trauma exposure and epigenetic patterns that may account for physiological and behavioral outcomes of offspring (Aoued et al, 2020;Dias et al, 2015a;Dias & Ressler, 2014;Feldman et al, 2019;Klengel et al, 2016;Klosin & Lehner, 2016;Rodgers et al, 2015;Ryan & Kuzawa, 2020;Wu & Suzuki, 2006).…”

“…However, when exposed to a different odor, the offspring showed no enhanced responses (Dias & Ressler, 2014). Recently, this research group reproduced this effect with olfactory fear conditioning to a specific odor using extracted sperm RNA (Aoued et al., 2020). Though the specific biological mechanism through which this phenomenon occurs is currently unknown, this and other recent promising animal work demonstrate the possibility of paternal stress affecting offspring mammal biology through changes in sperm microRNA, which may recapitulate DNAm patterns postgamete formation (Chuang & Jones, 2007; Hehar et al., 2017; Mashoodh & Champagne, 2019; Morgan et al., 2019; Rodgers et al., 2013, 2015; Scorza et al., 2019).…”

“…While epigenetic reprogramming of the germline in mammals (Heard & Martienssen, 2014) involves global demethylation and remethylation during embryogenesis (Bogdanović & Lister, 2017), some low levels of DNAm are preserved (Heard & Martienssen, 2014). Additionally, animal work has elucidated paternal effects of trauma exposure and epigenetic patterns that may account for physiological and behavioral outcomes of offspring (Aoued et al., 2020; Dias et al., 2015a; Dias & Ressler, 2014; Feldman et al., 2019; Klengel et al., 2016; Klosin & Lehner, 2016; Rodgers et al., 2015; Ryan & Kuzawa, 2020; Wu & Suzuki, 2006).…”

Inheritance of Acquired Traits in Insects and Other Animals and the Epigenetic Mechanisms That Break the Weismann Barrier

“…This behavioral response in the offspring was similar to that of the treated parent. Differentially expressed miRNAs that contributed to the increased sensitivity of the mice to the odor, and enhanced olfactory-related neuroanatomy, were identified in sperm from the odor-exposed parent mice relative to the control parents [44]. This study showed paternal influence in the inheritance of a learned behavior mediated by sncRNAs.…”

Fear conditioning biases olfactory stem cell receptor fate

“…Aversive olfactory conditioning in mice results in the persistent avoidance of the conditioned odor, and the olfactory sensory neurons (OSNs) responsive to this odor increase in number in the sensory epithelium (Jones et al, 2008). Strikingly, this increase in the number of specific sensory neurons was observed not only in trained F0 males, but also in their offspring (F1), despite the fact that the progeny had never been exposed to the conditioned odor (Dias & Ressler, 2014;Aoued et al, 2019;Aoued et al, 2020). This phenomenon, intergenerational epigenetic inheritance, invokes the transfer of information from one generation to the next without alterations to the sequence of the genome.…”