Probing the roles of medial frontal cortical neurons and neuromodulators in decision making

Andrew Holmes’ Lab (NIH/NIAAA) and Armin Lak’s Lab, Oxford University

Several decades of research has shown that medial frontal cortical neurons, as well as the neuromodulatory system that innervate the medial frontal cortex, notably the dopamine system, are important in reward valuation and decision making. However, it is not known whether different regions of medial frontal cortex play distinct roles in guiding decisions. Moreover, the role of frontal dopamine signals in shaping and regulating decisions has yet to be established. To address these questions, this project will use a combination of large-scale Neuropixels recording across the medial frontal cortex, as well as optical measurement of dopamine release in the medial frontal cortex during decision making in mice. At Oxford, the project will use Neuropixels probes to record the activity of many neurons across different regions of medial frontal cortex while mice perform a task that systematically manipulates the value of choice options. This data will allow us to investigate the relation between frontal neuronal activity and decision-making variables, and characterize distinct roles of different medial frontal regions in choice behavior. At NIH, the project will take advantage of optical and genetic methods to measure the dynamics of dopamine release in frontal cortical regions identified in the electrophysiological recordings. These experiments will reveal the roles that frontal dopamine play during decision making. In analyzing the electrophysiological and optical data, we will use computational models of learning and decision making to relate neuronal signals with trial-by-trial model-driven estimates of decision variables. The project is primarily experimental in nature but will provide an opportunity to develop computational skills. Together, the project will provide fundamental insights into behaviorally-relevant computations that neurons across the medial frontal cortex perform during decision making, and will reveal the roles of frontal dopamine signals in shaping choice behavior. For more information please visit: https://www.niaaa.nih.gov/laboratory-behavioral-and-genomic-neuroscience and https://www.laklab.org.

*This project is available for the 2021 Oxford-NIH Pilot Programme*