The neurotransmitter dopamine (DA) plays a critical role in reward, motivation, and decision making. DA circuits are altered in numerous psychiatric disorders such as depression, schizophrenia, and addiction. The ability to quantify the release of DA in various neural circuits can help us better understand the underlying neural mechanisms of psychiatric disorders. A recently developed method, fiber photometry, allows for direct measurement of the DA release at a neural synapse. Using a viral vector, a novel fluorescent indicator known as dLight is expressed on a cell membrane. When neurons nearby are stimulated to release DA, the DA will bind to dLight on the target cell, resulting in the release of a fluorophore. The amount of fluorescence can then be measured by an implanted fiber optic cannula and light sensor. Given the complexity of this method, and its relative novelty in the field, the purpose of this project is to develop and validate methods for its use in awake and behaving animals. To accomplish this, we plan 3 experiments: In experiment 1 and 2, using a stimulating electrode implanted in the ventral tegmental area (VTA) we will evoke a DA release from the VTA to the nucleus accumbens (NAc), a circuit known to be involved with reward. In experiment 1, animals will be anesthetized using isoflurane and we expect to see an increase of fluorescence in response to the VTA stimulation. Experiment 2 will consist of awake behaving animals that will receive a VTA stimulation. We expect to see a higher increase in measured fluorescence in response to the stimulation than in experiment 1. In experiment 3, animals will be trained in a classical conditioning paradigm where a tone predicts the delivery of a reward (sugar pellet). It is expected that in the early phase of this experiment we will see a spike in fluorescence in response to the reward delivery. In the late phase, we expect the animal to learn the relationship between the tone and reward delivery, therefore we expect to see an increase in fluorescence in response to the tone alone, and a reduction in fluorescence when a reward is not given following the tone. This project will allow for fiber photometry to be used in research studying how changes in dopaminergic activity can alter reward, motivation, and decision making, potentially leading to new therapeutics for these disorders.
Author: Cayla Bodner
Faculty Advisor: Matthew McMurray, Department of Psychology
Graduate Advisor: Danielle Tapp, Department of Psychology
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