The Role of Local Activity of the Nucleus Accumbens in Reward: Interneurons and Gamma Oscillations

Abstract

The nucleus accumbens (NAc) is a brain structure essential for an animal's ability to adapt its behavior and choices to changes in its surrounding environment. It receives convergent information from many brain regions about environmental stimuli and internal drives and integrates this information to function as a gatekeeper to the basal ganglia. Numerous classes of interneurons and local processes modulate the afferent inputs and contribute to the ultimate summation of this information, which is then relayed to the basal ganglia by medium spiny neurons. In this dissertation, we investigated the role of cholinergic interneurons (CINs) of the nucleus accumbens, and how they interact with dopaminergic (DA) terminals from the ventral tegmental area (VTA) to alter DA release, as well as the role of gamma-frequency local field potentials in reward behaviors. Using genetically targeted optical excitation of CINs in ChAT-Cre mice in combination with adenoassociated viral vectors containing a double-floxed open reading frame Channelrhodopsin gene, we recorded DA release using fast-scan cyclic voltammetry (FSCV) in anesthetized mice. We found that CINs can directly evoke DA release in the accumbens without coincident stimulation of DA terminals. We then tested if optical stimulation of CINs would produce similar reinforcing effects to pharmacological manipulation of DA in behaving mice, using place preference paradigms. However, no significant reinforcing effects of accumbal CIN stimulation were observed under our experimental conditions. We concluded that CIN-stimulation is not reinforcing. Next, we investigated the role of accumbal low and high gamma oscillations during food-reward operant tasks. We found differential activity of low and high gamma bands associated with different aspects of reward. Specifically, we find a representation of reward value in low gamma, as well as a representation of reward prediction error in high gamma. We conclude that high and low gamma oscillations accompany reward pursuit in mice during operant tasks, and that they exhibit distinct activity patterns to different aspects of reward.