This award is jointly made by two programs: the Instrument Development for Biological Research program (IDBR) and Emerging Frontiers (EF) in the Directorate of Biological Sciences (BIO).
The neurotransmitter dopamine plays a central role in learning, decision making, motivation, and the control of movement. It is assumed that dopamine influences these functions by modulating the capacity of individual neurons to form brief or lasting connections with other neurons. This assumption, however, has not been tested as no instrument exists for the real-time measurement of both dopamine release and the activities of groups of individual neurons in freely-moving animals. To build such a device the following will be combined: fast-scan cyclic voltammetry, the current state-of-the-art technology for measuring dopamine release, and high-density extracellular electrode arrays for the real-time measurement of large groups of individual neurons. The instrument will be designed for recording in freely-behaving animals, giving scientists the unprecedented opportunity to address questions such as: Is communication between neurons in distant brain regions enhanced by dopamine release? Does such enhanced communication correspond with improvements in learning, decision making, or motor control? Does dopamine release during sleep coordinate the reactivation of neurons involved in a recent learning experience? Is such reactivation important for the formation of long-term memories? The societal impact of addressing questions such as these would be in the fundamental advances answers would bring to the understanding of the brain as an integrated system, how this system works during learning and decision making, and what goes wrong when components of this system break down due to neurological disease or injury.
No tool exists that enables researchers to investigate the link between the activities of large groups of individual neurons and dopamine release in freely-behaving animals. The goal of this project is to build an instrument capable of measuring dopamine release and the activity of 100s of simultaneously active neurons in awake and behaving animals. The instrument integrates state-of-the-art technologies for measuring dopamine (fast-scan cyclic voltammetry) and neural activity (high-density ensemble recording). These technologies have not been integrated due to technical limitations. For example, electrical pulses created during voltammetry interfere with neural recording. Our methods are 1) adapt a recently-developed multi-channel headstage amplifier into our recording system that rapidly adapts to electrical artifacts, and 2) develop a novel carbon-film coating for metal electrodes, permitting dopamine recordings from electrode arrays. Our approach is to identify technical hurdles by troubleshooting and collecting scientific data from the system in anesthetized and freely-behaving rats. The two-year scope of this study is to collect and publish scientific and technical data from fully functional prototypes. These data will support funding efforts to build and distribute a commercial product. The theoretical foundation inspiring this work is that dopamine modulates decision making, learning, and motor control through its ongoing regulation of plasticity and neural activity in neuronal groups. According to the reinforcement-learning theory of dopamine function, dopamine release following unexpected rewards triggers associative learning and plasticity in networks of neurons. The question of how activity and connectivity are regulated by dopamine in behaving animals is unanswered and the proposed instrument will help fill this gap in understanding.
