The neural mechanisms that underlie drug and alcohol relapse is a major unsolved problem addiction neuroscience research. Reward-predictive cues are thought to play an important role in relapse and elicit pronounced neural activity in the basal nucleus of the amygdala (BA). Interestingly, the BA is highly active in human addictive disorders and both sends and receives a variety of projections from both classical decision- making areas, such as the orbital frontal cortex (OFC), and classical """"""""reward"""""""" regions, such as the nucleus accumbens (NAcc). Given the behavioral and neural-network relevance of the BA, it may play a key role in the establishment and maintenance of the neural link between cue and reward. It is not known, however, what features of the cue-evoked activity are represented within the BA, as the BA has previously been shown to encode features such as outcome-valance and salience. This proposal aims to explore the informational content of cue-evoked activity within the BA with the hypothesis that the BA represents the strength of cue-outcome associations (such that cues that signal a low-certainty outcome will exhibit differential firing rates than those cues that signal a high-certainty outcome) and that the BA serves to inform downstream decision- making regions such as the OFC. This study will utilize chronic in vivo electrophysiology in awake, behaving rodents in a forced-choice discrimination task and ambiguous cues. It can then be determined if cue-evoked responses in the BA are modulated by the strength of cue-outcome associations (Aim 1), if this modulation is dependent on the decision-making process (Aim 2), and how the BA influences downstream regions involved in decision making (Aim 3). Together, these studies will elucidate the role of the amygdala in reward-predictive cue processing, particularly the representation of cue-outcome associations and the BA's role in informing decision-making. Understanding these neural circuits of addiction and relapse is the first stage in developing effective treatments for human addiction diseases.
The proposed research seeks to explore the neural encoding of reward-predictive cues within the amygdala using rodent animal models related to drug-abuse, addiction, and relapse. In both human and animal models, reward - or drug - predictive cues elicit pronounced activity within the frontal and limbic reward networks in regions such as the OFC and amygdala. Identifying and understanding the important features of cortical responses within these networks will allow a greater understanding of the underlying neural circuitry of addiction and guide therapeutic interventions.
