Abstract
While it is clear that behavioral experience modulates epigenetic profiles, it is less evident how the nature of that experience influences outcomes and whether epigenetic/genetic “biomarkers” could be extracted to classify different types of behavioral experience. To begin to address this question, male and female mice were subjected to either a Fixed Interval (FI) schedule of food reward, or a single episode of forced swim followed by restraint stress, or no explicit behavioral experience after which global expression levels of two activating (H3K9ac and H3K4me3) and two repressive (H3K9me2 and H3k27me3) post-translational histone modifications (PTHMs), were measured in hippocampus (HIPP) and frontal cortex (FC). The specific nature of the behavioral experience differentiated profiles of PTHMs in a sex- and brain region-dependent manner, with all 4 PTHMs changing in parallel in response to different behavioral experiences. These different behavioral experiences also modified the pattern of correlations of PTHMs both within and across FC and HIPP. Unexpectedly, highly robust correlations were found between global PTHM levels and behavioral performances, suggesting that global PTHMs may provide a higher-order pattern recognition function. Further efforts are needed to determine the generality of such findings and what characteristics of behavioral experience are critical for modulating PTHM responses.
Highlights
The importance of behavioral history to the nature of subsequent behavioral and brain function has long been recognized (Barrett, 1986; Pattij et al, 2004; Marchner and Preuschhof, 2018) and can include differential behavioral responses to subsequent drug treatments, or even the maintenance of such seemingly incongruous behavior as response-produced shock that can emerge following specific behavioral histories (Byrd, 1972)
To evaluate the role of different types of behavioral experience, the current study examined differences in epigenetic profiles in mice that had been subjected to a fixed interval (FI) schedule of food reward which consisted of earning food rewards via a lever press response that were available after Fixed Interval (FI) of time, or to a single episode of forced swim followed by a single episode of restraint stress, or to no explicit behavioral experience
Male-specific differences in global post-translational histone modifications (PTHMs) levels in frontal cortex (FC) in relation to behavioral experience conditions were found for H3K27me3 [F(2,14) = 4.43, p = 0.036] which reflected the higher levels of this mark in mice that had FI behavioral experience (p = 0.0124), compared to those with Forced Swim-Restraint Stress (FS-RS) behavioral experience, with a similar trend (p = 0.061) evident for H3K9ac in males
Summary
The importance of behavioral history to the nature of subsequent behavioral and brain function has long been recognized (Barrett, 1986; Pattij et al, 2004; Marchner and Preuschhof, 2018) and can include differential behavioral responses to subsequent drug treatments, or even the maintenance of such seemingly incongruous behavior as response-produced shock that can emerge following specific behavioral histories (Byrd, 1972). Intervention programs such as Head Start, have been shown to result in long-term benefits in school achievement, grade retention, special education placement, and social adjustment (Barnett, 1995). Parallels exist in animal models using environmental enrichment. Such enrichment is achieved in several different forms, Global Histones Correlate With Behavior both social and physical, with multiple reports showing its ability to produce beneficial effects (Hirase and Shinohara, 2014; Kelly, 2015; Kondo, 2017). Adverse behavioral experiences have persistent and profound damaging effects, both cognitive and emotional. Institutionalization or being raised in an orphanage, as deprivation-related adversities, resulted in developmental delays in social, behavioral and cognitive domains (Chugani et al, 2001; Johnson et al, 2006). The long-lasting temporal influence of behavioral experience has invoked a variety of mechanistic explanations, most notably epigenetic mechanisms
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