Date of Award
Spring 2022
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Neuroscience
First Advisor
Kwan, Alex
Abstract
In a social game involving two animals, the outcome depends on the choices of both. Thriving in such situations requires the animal to make flexible decisions against its opponent to gain reward which is essential to survive. Central neuromodulatory systems have been shown to send broad projections to various brain regions, and contribute to the regulation of information processing. However, it remains unclear that what roles the noradrenergic and cholinergic signals play in the frontal cortex during value-based decisions. To directly address this question, the dissertation will present two independent studies centered on the neuromodulation during decision-making. We first trained the head-fixed mice to play a competitive game called ‘matching pennies’, demonstrating the feasibility of mice making flexible decisions under competitive pressure against a computer opponent. The behavior of the animals can be well fit under the framework of model-free reinforcement learning. Moreover, we compared the animal’s behavior with a dynamic foraging task, a widely used non-competitive behavior paradigm in value-based decisions, showing that the animals play the matching pennies game under a reinforcement learning regime that is different from the dynamic foraging task. To investigate the effect of global neuromodulation on the behavior of animals during the competitive game, we measured the trial-by-trial pupil responses and applied multiple linear regressions to relate the pupil transients with decision-related variables. Our results suggest that pupil responses are modulated by choice, outcome, and latent variables for value-updating but not choice-selection. Next, we characterized the noradrenergic and cholinergic transients in the medial frontal cortex with two-photon fluorescent imaging. With similar multiple linear regression models, we link the fluorescent signals to decision-related variables. We found that both norepinephrine and acetylcholine activity are modulated by choice, outcome, and reinforcers. Furthermore, acetylcholine but not norepinephrine transients multiplex the task-related information. We examined the spatial and temporal heterogeneity of both neuromodulators, which hinted that the phasic acetylcholine and norepinephrine activity may mediate different downstream computation in value-based decisions. Collectively, these findings established a social behavior paradigm in mice to investigate value-based decisions under competitive pressure, and highlighted different dynamics of norepinephrine and acetylcholine signals in the medial frontal cortex during the competitive behavior.
Recommended Citation
Wang, Hongli, "Frontal Neuromodulation of Value-Based Decisions in Mice Playing a Competitive Game" (2022). Yale Graduate School of Arts and Sciences Dissertations. 902.
https://elischolar.library.yale.edu/gsas_dissertations/902
