Grant: Discovery Grants Program - Individual

Have you ever wondered why students glance at their phones so often? Just as unpredictable reward increases motivation in animals, perhaps the thrill of an unexpected notification is responsible for the draw of social media. Why does uncertainty hold such allure? This proposal aims to uncover the underlying mechanisms that make random reward schedules so enticing. We will evaluate three models proposed to explain this phenomenon. One suggests that when the ratio of responses per reward is random (i.e., a random-ratio schedule), the occasional short-latency rewards are over-weighted, leading to over-valuation of the entire schedule. The other two suggest that random ratio schedules increase dopamine release, either because the unpredictability increases reward prediction errors resulting in phasic dopamine bursts, or because the uncertainty itself increases tonic dopamine levels. These theories will be tested via three specific aims, each using a different experimental paradigm. Aim 1 seeks to directly measure dopamine in ventral striatum while rats are responding for reward on either a random-ratio or fixed-ratio schedule. Towards this end, I will use an genetic dopamine indicator and an implanted optical fiber (fiber photometry). Through this experiment, I seek to determine whether random schedules increase phasic or tonic dopamine. Aim 2 explores which subtypes of dopamine receptors (e.g., D1, D2 or D3) are important for the motivational aspects of random reward schedules. Rats will be given different dopamine receptor agonists and antagonists while their preference for a random over a predictable (i.e., fixed-ratio) reward schedule is measured. We will also explore the role of dopamine receptor subtypes in a related task involving uncertainty: the N-arm bandit task. In this task, reward probability for three response ports varies slowly and rats must balance the benefits of sticking with a known port against exploring for better options, which might or might not be fruitful. Combined, these experiments should point to the aspects of cortical-striatal circuitry that are most important for the attraction of random-ratio schedules. Aim 3 investigates the computational basis of random schedule preference, recording the responses of cell populations in the rat prefrontal cortex and ventral striatum. We will compare firing rates related to response initiation, reward anticipation, and reward delivery under both random- and fixed-ratio schedules. The goal is to determine when firing rates show the greatest differences between random- and fixed-ratio schedules. Importantly, specific predictions of each of the aforementioned theories will be tested. Together, these findings will solve the enduring mystery of why random ratio schedules are so alluring. More broadly, they also will shed light on the functions of dopamine in the brain reward circuits, helping us better understand the neural bases of learning and motivation.