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Investigating the Interactions of Neuromodulators: A Computational Modeling, Game Theoretic, Pharmacological, Embodiment, and Neuroinformatics Perspective

  • Author(s): Zaldivar, Andrew
  • Advisor(s): Krichmar, Jeffrey L
  • et al.

Neuromodulatory systems originate in nuclei localized in the subcortical region of the brain and control fundamental behaviors by interacting with many areas of the central nervous system. Much is known about neuromodulators, but their structural and functional implications in fundamental behavior remain unclear. This dissertation set out to investigate the interaction of neuromodulators and their role in modulating behaviors by combining methodologies in computational modeling, game theory, embodiment, pharmacological manipulations, and neuroinformatics. The first study introduces a novel computational model that predicts how dopamine and serotonin shape competitive and cooperative behavior in a game theoretic environment. The second study adopted the model from the first study to gauge how humans react to adaptive agents, as well as measuring the influence of embodied agents on game play. The third study investigates functional activity of these neuromodulatory circuits by exploring the expression energy of neuromodulatory receptors using the Allen Brain Atlas. The fourth study features a web application known as the Allen Brain Atlas-Drive Visualization, which provides users with a quick and intuitive way to survey large amounts of expression energy data across multiple brain regions of interest. Finally, the last study continues exploring the interaction of dopamine and serotonin by focusing specifically on the reward circuit using the Allen Brain Atlas. The first two studies provide a more behavioral understanding of how dopamine and serotonin interacts, what that interaction might look like in the brain, and how those interactions transpire in complex situations. The remaining three studies uses a neuroinformatics approach to reveal the underlying empirical structure and function behind the interactions of dopamine, serotonin, acetylcholine and norepinephrine in brain regions responsible for the behaviors discussed in the first two studies. When combined, each study provides an additional level of understanding about neuromodulators. This is of great importance because neuroscience simply cannot be explained through one methodology. It is going to take a multifaceted effort, like the one presented in this dissertation, to obtain a deeper understanding of the complexity behind neuromodulators and their structural and functional relationship with each other.

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