Epigenetic-Based Evidence for Distinct Effects of Age, Sex, and Experience in Developmental Critical Period Learning

Although much is known about the encoding of experience, how the brain organizes neural circuits capable of learning and memory formation is largely unstudied. Canonical critical periods emerge from a convergence of maturation- and experience-dependent processes. Notably, they rely on experience itself to close, resulting in permanent traces of early life. Mechanisms of perceptual critical periods have been well studied, but cognitive critical periods are rare and poorly understood. One well-established critical period for learning is in the juvenile male zebra finch songbird. Juvenile females also perform sensory song learning at ages that overlap with those of the male critical period, though females may learn outside of its age boundaries. The examination of critical period closure thus allows for mechanistic evaluation of the convergence of maturation and experience, plus it provides a unique opportunity to identify neural factors that promote or limit the ability to learn. Because regulated transcription is necessary for the organization and function of cells and circuits, we used a discovery tool (ChIP-seq) for H3K27ac, a strong epigenetic marker of active promoters and enhancers. We examined male and female auditory forebrain, a region necessary for sensory song learning, at two ages and under rearing conditions that affect male critical period closing. We report specific transcription factors, genes, and biological processes that may promote and limit the ability to learn in males, evidence for fluctuations in female developmental plasticity, and evidence that males and females successfully perform sensory song learning using distinct mechanisms.