Early life experiences program brain structure and function and contribute to 
behavioral endophenotypes in adulthood. Epigenetic control of gene expression by 
those experiences affect discrete brain regions involved in mood, cognitive 
function and regulation of hypothalamic-pituitary-adrenal (HPA) axis. In 
rodents, acute restraint stress increases the expression of the repressive 
histone H3 lysine 9 tri-methylation (H3K9me3) in hippocampal fields, including 
the CA3 pyramidal neurons. These CA3 neurons are crucially involved in cognitive 
function and mood regulation as well as activation of glucocorticoid (CORT) 
secretion. CA3 neurons also exhibit structural and functional changes after 
early-life stress (ELS) as well as after chronic stress in adulthood. Using a 
protocol of chronic ELS induced by limited bedding and nesting material followed 
by acute-swim stress (AS) in adulthood, we show that mice with a history of ELS 
display a blunted CORT response to AS, despite exhibiting activation of 
immediate early genes after stress similar to that found in control mice. We 
find that ELS induced persistently increased expression of the repressive 
H3K9me3 histone mark in the CA3 subfield at baseline that was subsequently 
decreased following AS. In contrast, AS induced a transient increase of this 
mark in control mice. Using translating ribosome affinity purification (TRAP) 
method to isolate CA3 translating mRNAs, we found that expression of genes of 
the epigenetic gene family, GABA/glutamate family, and glucocorticoid receptors 
binding genes were decreased transiently in control mice by AS and showed a 
persistent reduction in ELS mice. In most cases, AS in ELS mice did not induce 
gene expression changes. A stringent filtering of genes affected by AS in 
control and ELS mice revealed a noteworthy decrease in gene expression change in 
ELS mice compared to control. Only 18 genes were selectively regulated by AS in 
ELS mice and encompassed pathways such as circadian rhythm, inflammatory 
response, opioid receptors, and more genes included in the glucocorticoid 
receptor binding family. Thus, ELS programs a restricted translational response 
to stress in stress-sensitive CA3 neurons leading to persistent changes in gene 
expression, some of which mimic the transient effects of AS in control mice, 
while leaving in operation the immediate early gene response to AS.