"Dissecting the Role of Neuromodulators in Value-Based Decision Making" by Heather Ortega

Date of Award

Spring 2024

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Interdepartmental Neuroscience Program

First Advisor

Kwan, Alex

Abstract

Neuromodulators such as acetylcholine (ACh) and norepinephrine (NE) play diverse roles in the central nervous system. Structurally they are organized to exert a coordinating force over many brain regions as their nuclei project widely. Functionally both neuromodulators serve basic functions including arousal and attention as well as more complex roles such as learning and reinforcement. More interestingly, new evidence points to a distinct cognitive utility where ACh may influence learning and NE promotes stochastic choice. Evidence for these roles comes primarily from pharmacological depletion studies, recording from nuclei, and Pavlovian or sensory-cue guided tasks. However, the computational roles of NE and ACh remain largely unknown. Specifically, their function on a sub second timescale or during tasks that require continuous learning. To address these questions, this dissertation will first present the building and characterization of a photostimulation system to manipulate neural dynamics precisely and causally during head-fixed rodent decision making. The system’s precision and reliability were quantified by measuring laser beam width and positioning. Additionally, we measured the rig’s effect on neural activity and ability to manipulate behavior during a decision making task. Second, this dissertation will present a study designed to test the roles of NE and ACh across cortex and under competitive pressure. When NE release is stimulated from axons in secondary motor or primary visual cortex, mice tend to explore more. We found this to be true when the mice were under competitive pressure in a ‘Matching Pennies’ game as well as in a simple choice task with no inherent benefit to stochasticity. Mice demonstrated no such tendency when the cholinergic system was stimulated. These results demonstrate the efficacy of this photostimulation system and evidence for norepinephrine’s role in promoting volatility.

Share

COinS