Neural circuits underlying reward-seeking behavior

My lab focuses on understanding the neural circuits responsible for reward-seeking and addictive behaviors. We use a systems-level approach that combines behavioral, pharmacological and electrophysiological techniques in awake, freely moving animals. We begin by identifying a hypothesis regarding the neural circuits underlying a particular behavior. For example, the nucleus accumbens (part of the ventral striatum) projects to motor output structures of the basal ganglia. The accumbens also receives input from limbic structures that have been suggested to process stimuli that predict events of consequence to the animal’s well-being. These limbic structures include the basolateral amygdala, which sends glutamatergic axons to the accumbens, and the ventral tegmental area (VTA), which sends a dopamine projection. Therefore, we hypothesized that the amygdala and VTA projections to the accumbens are part of the neural circuit that controls the animal’s response to reward-predictive stimuli.

To test this hypothesis, we designed a behavioral task that requires rats to respond, by pressing a lever, to an auditory stimulus that predicts sucrose reward. We then determined that the dopamine projection to the accumbens is required for this behavior by demonstrating that dopamine receptor antagonists microinjected directly into the animals’ nucleus accumbens caused animals to cease responding to the stimulus. We also showed that transient inactivation of the amygdala had the same effect. Next, we used multiple simultaneous single-unit recordings of neurons in the accumbens and amygdala to demonstrate that subpopulations of neurons were excited or inhibited by the reward-predictive stimulus. Finally, we established that stimulus-evoked excitations and/or inhibitions in the accumbens are required for the reward-seeking behavior instigated by the stimulus. We did this by inactivating either the dopaminergic VTA neurons or amygdala neurons while recording from accumbens neurons during the stimulus-evoked reward seeking task. Inactivation of either structure selectively abolished the firing of accumbens neurons responsive to reward-predictive stimuli. These experiments established that the convergence of the excitatory projection from the amygdala and dopaminergic projection from the VTA in the accumbens is an important part of the neural circuits that underlie stimulus-evoked reward-seeking behavior. Ongoing experiments seek to determine the nature of the information encoded by the firing of accumbens neurons driven by the amygdala and dopamine projections.

Drugs of abuse can also serve as rewards, often to the extent that drug-seeking (sometimes in response to drug-predictive stimuli) becomes excessive and harmful. A long-term goal of these experiments is to use our increasing knowledge of the neural circuits that control reward-seeking to ask how these circuits produce aberrant behavior (excessive drug-seeking) in addiction.