Histone deacetylase inhibition induces long-lasting changes in maternal behavior and gene expression in female mice

Abstract

Inmanyspecies, including mice, maternal responsiveness is experience-dependentandpermanent, lasting for long periods (months to years).Wehave shown that after brief exposures to pups, virgin female mice continue to respond maternally toward pups for at least one month. Administration of a histone deacetylase inhibitor (HDACi) reduces the amount of maternal experience required to affect maternal behavior and gene expression. In this set of studies, we examined the epigenetic mechanisms that underlie these motivated behaviors. We assessed whether the effects of HDACi persisted 1monthafter the initial experience (in the absence of continuedpupexperience or HDACi treatment) and whether the maintenance of maternal memory was associated with stable changes in gene expression. Using chromatin immunoprecipitation, we examined whether Esr2 and Oxt gene expression might be mediated by recruitment of the histone acetyltransferasec AMP response element binding protein (CBP) to their promoter regions after maternalmemoryconsolidation. We report that HDACi treatment induced long-lasting changes in maternal responsiveness. Maternal learning was associated with increased recruitment of CBP to the Esr2 and Oxt gene promoters during the consolidation of maternalmemoryas well as a persistent increase in estrogen receptor-β (Esr2) mRNA and decreased expression of the de novo DNA methyltransferase Dnmt3a within the medial preoptic area. The consolidation of the maternal experience may involve the CBP recruitmentandstable changes ingeneexpression, which maintain increased maternal responsiveness for long periods of time. Copyright