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.