Cortical neuromodulatory mechanisms underlying adaptation and plasticity

PROJECT SUMMARY During our previous studies, we established synaptic zinc as a powerful neuromodulator of synaptic transmission, synaptic plasticity, and sound processing. Based on these findings and our preliminary results, we propose that cortical synaptic zinc is a crucial neuromodulator for cortical adaptation and plasticity (recovery) after noise trauma (peripheral damage). Namely, we plan to answer two main questions: 1) What are the cell- type-specific zincergic neuromodulatory mechanisms underlying cortical adaptation to different background sound statistics? And 2) How do cell-type-specific zincergic neuromodulatory mechanisms contribute to cortical and perceptual recovery after peripheral damage? Answering these questions will advance the field to a new level of understanding about cortical neuromodulatory mechanisms during normal and pathological sensory processing, and create a new framework for approaching and interpreting cortical adaptation and plasticity. Importantly, our proposed studies hold the potential to highlight novel strategies for enhancing hearing after hearing loss, and for mitigating disorders that are associated with maladaptive central plasticity after peripheral damage, such as hyperacusis and tinnitus