Simultaneous RNA Sequencing and DNA Methylation Profiling Reveals Neural Mechanisms That Regulate Sensitive Period...

Developmental processes emerge from both maturational and experience-dependent mechanisms. Experience at the proper maturational stage is essential for the acquisition of many complex cognitive and behavioral processes. A striking example of this is a critical period, a restricted developmental phase during which experience is required for both behavioral acquisition and period closure. Juvenile male zebra finches (Taeniopygia castanotis) possess a critical period for song learning; hearing an adult "tutor's" song between posthatch days 30-65 is necessary for each male to produce a socially functional adult song. However, if tutor song is not experienced in this age range, juveniles can still learn beyond posthatch day 65. Our broad objective is to decipher the neurogenomic mechanisms that promote or limit the ability to learn, leveraging the known parameters of the critical period in the male zebra finch's sensory song learning ontogeny. Here, we manipulated juvenile males' tutor exposure and provided song playback experience at two ages, at the beginning or end of the critical period. We probed the relationship between DNA methylation and transcriptional profiles from the same individual and tissue samples to enhance interpretation across different levels of biological organization. Our findings uncovered specific genes and processes that may regulate aspects of critical period learning, as well as aspects of DNA methylation dynamics and how they correspond to RNA measures. Because we distinguished effects of age and experience, outcomes provide insight into fundamental links between epigenetic and molecular properties as the developing brain shifts its ability to learn.