My research examines how the brain processes information about rewards, and how that information is used to guide goal-directed actions. Reward-related processing is complex, involving mechanisms of learning, memory, motivation, decision-making and movement. I strive to tease apart these components on a neural level under normal conditions, and understand how this system becomes maladaptive in drug addiction. My lab takes a multidisciplinary approach in rodent models to pursue these goals. At the core of this work is the development of sophisticated behavioral tasks that enable us to examine discrete aspects of reward processing. We then combine our behavioral designs with various methodologies including multi-neuron recording, electrochemistry, iontophoresis and optogenetics. Below is a brief overview of some topics currently under investigation in my lab.
Dissecting the Functional Microcircuitry of Brain Reward Processing
A primary focus of my research has been to understand the functional organization of a key neural substrate of the brain reward circuit, the nucleus accumbens (NAc). Using multi-neuron recording in behaving rats, our early work established the existence of distinct functional ‘microcircuits’ in the NAc. These microcircuits are not ‘hard-wired’ to process different aspects of reward, but instead are highly dynamic and influenced by a multitude of factors including, for example, reward type. Virtually all rewards (both drug and natural) activate the mesolimbic dopamine system; most notably via inputs to the NAc. Using an interdisciplinary approach, we employ electrochemical tools to examine rapid dopamine signaling in the NAc during behavior. We showed dynamic dopamine release during reward-seeking behaviors for food and intravenous cocaine, as well as during associative learning. Importantly, this signaling differs under aversive circumstances. Further, using a combined electrochemistry & electrophysiology method developed in the lab of Mark Wightman (UNC Chemistry) we revealed that dopamine release only occurs at locations where NAc neurons encode distinct features of goal-directed actions. In ongoing investigations, we are employing a modified iontophoresis method that is used during behavior to take our analysis of this microcircuit function to the receptor level.
Neurobiological Investigation of Decision-Making
Dopamine signaling in the NAc scales with the costs associated with actions, placing this neural substrate in a critical juncture in the decision-making process. We use electrochemical methods to examine dopamine release dynamics in ‘real time’ during cue periods in our tasks when rats are evaluating their options and making decisions to act. We have shown that dopamine release scales with more preferred options in decision making tasks involving, effort, delay and risk. Ongoing research seeks to provide insight into how NAc circuitry encodes and controls decision-making under normal conditions using electrochemistry, electrophysiology and optogenetics, and determine how a history of cocaine can alter aspects of this processing. The later is clinically relevant since several psychiatric diseases, including drug addiction, are believed to reflect maladaptive decision making linked with altered dopamine function.
Unraveling Neurobiological Mechanisms of Cocaine Addiction
The DSM-V recognizes the emergence of negative affect (e.g., dysphoria, irritability, anhedonia) in addiction, where prior rewarding experiences (e.g., food, job) become devalued as the addict continues to seek and use drug despite harmful outcomes. We continue working with a novel behavioral model we developed of natural reward devaluation by cocaine where we showed that a drug-associated cue elicits a conditioned aversive state that is quantifiable in terms of behavior, neural and chemical processing and, critically, predicts subsequent cocaine consumption. Other related lines of research are examining the neurobiological consequences in the NAc of drug removal (abstinence, known to exert numerous neuroadaptations linked to relapse), how a history of cocaine alters aspects of associative learning, and the role of reward choice in normal versus addicted states. In addition, we are examining processing within the larger neural circuit in which the NAc is embedded, including for example, reward-processing within the basolateral amygdala and prefrontal cortex.