Title: Optogenetic and chemogenetic sensors and tools for studying brain signaling

Abstract: G-protein coupled receptors (GPCRs), such as dopamine and opioid receptors, play critical roles in neuromodulation. It remains a major challenge to record or manipulate GPCR signaling events both with high spatial resolution and across a large brain volume. Fast Scan Cyclic Voltammetry and microdialysis allow the study of neuromodulator release events in the brain. However, they do not provide a cellular-resolution map of neuromodulators. GPCR-based genetically-encoded real-time sensors enable the investigation of neuromodulators with high spatiotemporal resolution. However, they are limited to the recording of a small brain region and do not allow further study of the neuronal population of interest. My research group focuses on designing integration sensors that can integrate the neuromodulator signal into a permanent mark in the cells for further investigation. We have designed an opioid sensor with the potential for whole-brain mapping. We are also extending this design to detect other neuromodulators across the brain. Additionally, we are designing genetically-encoded chemical-activated opioid peptides to enable cell type-selective manipulation of opioid receptors to study their causal-effect on pain modulation and addition.