mPFC Regulation of VTA Dopamine and GABA Neuronal Activity During Flexible Updating of Appetitive and Aversive Associations

Oregon Health & Science University, Portland OR

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Abstract

Project Summary/Abstract In order to efficiently traverse an environment, one must learn to distinguish among cues that predict outcomes of different modalities, such as an appetitive reward or an aversive shock. In a dynamic environment where cues predicting rewarding or aversive outcomes unexpectedly change, it is adaptive to flexibly update behavioral responding while retaining the ability to recall previous associations. Impairments in the ability to appropriately respond to cues according to the outcome are evident in a number of psychiatric disorders. The overarching aim of my postdoctoral training is to better understand the neural circuitry responsible for updating previously learned cue-outcome associations. A large literature has implicated the ventral tegmental area (VTA) in the initial learning of appetitive and aversive associations. Both dopamine and γ-aminobutyric acid (GABA) neurons in the VTA are involved individually or cooperatively in different aspects of appetitive and aversive learning. After initial learning, I hypothesize that flexible responding to changes in outcome contingencies is modulated by the medial prefrontal cortex (mPFC) projections to the VTA in a valence-specific manner. To behaviorally quantify initial learning as well as updating cue-outcome associations, I will use a flexible contingency learning (FCL) task in which three distinct cues are paired with either an appetitive outcome (sugar pellet reward), an aversive outcome (mild foot shock), or no outcome. After learning, the appetitive and aversive outcomes reverse such that the cue previously paired with a shock will instead precede reward delivery and vice versa. I will be trained in fiber photometry recordings from VTA dopamine and GABA neurons as well as chemogenetic manipulation of the mPFC-VTA pathway to test whether the mPFC regulates flexible updating in a valence-specific manner. Regardless of the outcome, the proposed work will increase our understanding of the flexible updating of behavioral responding when outcome contingencies change.