PROJECT SUMMARY & ABSTRACT This goal of this project is to investigate epigenetic neural mechanisms that can ensure meaningful sounds are faithfully and adaptively represented in the adult auditory brain. One important aspect of this research concerns the precision of acoustic content in memory, which is important for learning and performing fine-tine auditory discriminations. A second, concerns long-term maintenance of experience via learning-induced neuroplasticity for strong auditory memory, which is relevant to maintain learned auditory abilities for life. Animals (including humans) use associative learning to link sound cues to salient events (like rewards or other significant outcomes). When neural mechanisms of memory formation are activated following these experiences—mechanisms that span from molecules to genes to circuits and systems—associative memory is formed, which in turn provides otherwise arbitrary sound with acquired significance. For example, in audition, communication abilities require that sounds are precisely linked with their learned meaning, which depends on neuroplasticity and enduring auditory memory that lasts from minutes, to hours and days, or a lifetime. Decades of research indicate that associative learning systematically changes the sensory cortex to alter representation of sensory cues with learned behavioral salience. But why do some individuals naturally form auditory memories stronger and more specifically than others? Epigenetic mechanisms that control chromatin acetylation by histone deacetylases (HDACs) likely function to control genes that ultimately establish changes to the auditory system that contribute to its plasticity and subsequent long-term auditory memory. Indeed, HDACs are capable of controlling how much auditory cortex changes with meaningful experiences, which may provide an instructive control on the auditory system as a whole for adaptive (or sometimes maladaptive) function. Currently unknown are the downstream gene and circuit mechanisms with which HDACs regulate auditory cortical plasticity. This proposal is for an administrative supplement that would promote diversity in the research team and in the field at large, here in particular to support a predoctoral trainee, Ms. Guan-En Graham, in her final PhD years. Her research is within the scope and critical to the completion of behavioral pharmacological and molecular work (parent AIM1) as well as viral (AIM2) techniques to manipulate HDAC3 in a rodent behavioral model of auditory associative learning to determine how HDACs alter the acquisition and initial storage of robust auditory memory. The studies will explain how HDACs regulate neuroplasticity from genes, molecules, circuits and systems for robust auditory behaviors with a system better “tuned-in” to important sounds. This research promotes neuroepigenetics and gene-discovery as an important new niche for auditory neuroscience. Trainee support will set the stage for Guan-En’s resear...