Summary. There is a dearth of information in any system about how developmental experiences have lasting influence on behavioral patterns. However, the multitude of examples of experiences directing typical, atypical, and therapeutic neurodevelopmental outcomes in humans and research animals indicates that the mechanisms by which experience-dependent plasticity modifies maturational programs in behaviorally-relevant brain circuits have broad implications. Why does our neurobiological understanding lag behind the behavioral evidence? Perhaps it is because linking juvenile experiences with adult behaviors requires a careful tracking of several timescales: from moment-to moment changes that occur rapidly with each relevant experience, to longer timeframes that take into account accumulated experiences, and the sustained backdrop of experience- independent maturational progression with which these experience-dependent changes intersect. No one measure or methodology can capture these dynamics. This is a large challenge, one that necessitates a research model that has strong, established experience-behavior links across development. The zebra finch songbird is such a model. In these birds, juvenile song experience has relevant and life-long consequences on adult patterns of social behavior in both males and females, in males, the structure of the song he sings his entire adult life and in females, her song and mate preferences; mate pairs stay together their entire lives. Song processing requires the higher-order association components of the auditory forebrain in males and females. Generally, it is obvious that epigenetic and molecular regulation of transcription and translation are at the core of neural plasticity, both maturational and experience-dependent, but it is not yet totally clear in any system how these mechanisms operate in concert to encode experiences during maturational stages such that they emerge as stable behaviors months and years later. Our published and preliminary data lead to our central hypothesis, that the specific mechanisms operating within the male and female juvenile auditory forebrain, while controlled by the same broad epigenetic and molecular regulatory processes, are distinct. To reduce the gap between observations of experience-behavior links and the mechanisms that mediate these connections, we have two current goals, 1) establish that adult behavior in both sexes is influenced by epigenetic and molecular processes as a result of accumulated and acute juvenile song experiences, 2) determine the extent to which specific mediators of cell structure and function are unique in juvenile male and female auditory forebrains. We will achieve these goals in three aims, which 1) test the role of histone H3 acetylation in gating the strength of juvenile song experiences on adult patterns of behavior and the regulatory transcription factors that may coordinate that link, 2) identify the “first wave” of epigenetic and molecular responses to hearing song that initiate neural remodeling, and 3) determine the extent to which molecular control of transcription and translation known to be necessary for adult behaviors differs by sex.

Narrative. Many adult behavioral patterns reflect experiences that occur when the individual is young, yet we have little mechanistic information about what happens to mediate this observation. Without addressing this gap, we risk missing significant opportunities to enhance positive or remediate adverse neurodevelopmental effects of experience. Here, we begin to fill this gap using a combination of epigenetic and molecular measures and manipulations of juvenile experience in males and females.