PhD Thesis Defense

Title: Optical imaging of dopamine dynamics and decoding its role in arousal and salience

Abstract: Dopamine (DA) is a key neuromodulator in the brain that can exert profound impact on brain physiology and cognitive functions. There is consensus that DA plays critical roles in reward prediction error, reinforcement learning and motor control, and that dysregulation of DA signaling is common in many neuropsychiatric diseases, such as Parkinson's disease, drug addiction, and depression. Although the tools to study the functional roles of DA have considerably expanded with novel genetic tools and optical imaging methods, we are still limited in our ability to record or visualize DA release in vivo with long-term stability and high spatiotemporal resolution. This is an unmet need in DA research, as DA release at the post-synaptic sites can be decoupled from DA cell body firing due to local circuit interaction and influence from other afferent activities. In parallel, there is growing evidence that DA is functionally heterogeneous beyond its classically described roles for reward and movement, based on its anatomical location, projection target, electrophysiological properties, and response patterns to stimuli with motivational valence. Pharmacological and genetic studies have provided indirect evidence that DA can promote strong behavioral arousal and signal salience, but the precise neural substrates for these functions remain largely unknown. Towards this end, my thesis work has been focused on 1) developing and characterizing optical tools to visualize DA release in vivo and 2) utilizing such optical and genetic tools to study the overlooked, sparse DA populations in the dorsal midbrain, demonstrating that they are functionally unique DA cells for broadcasting arousal and salience signals to the forebrain targets.