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

项目摘要/摘要 为了有效地遍历一个环境，一个人必须学会区分预测的线索 不同方式的结果，如渴望的奖励或厌恶的电击。在动态环境中 当预测奖赏或厌恶结果的线索意外改变时，它是适应灵活更新的 行为反应，同时保持回忆以前的联系的能力。能力上的损害 根据结果对提示做出适当的反应在许多精神障碍中都很明显。这个 我博士后培训的主要目的是更好地了解负责更新的神经回路 以前学过的线索-结果关联。 大量文献表明，腹侧被盖区(VTA)在最初的学习食欲和 令人厌恶的联想。VTA内的多巴胺和γ-氨基丁酸(GABA)神经元均参与其中 在好奇心和厌恶性学习的不同方面单独或合作。经过初步学习，我 假设对结果意外情况的变化的灵活反应是由中间人调节的 前额叶皮质(MPFC)以价态特异性的方式投射到VTA。从行为上量化首字母 除了学习和更新线索-结果关联，我将使用灵活的应急学习(FCL)任务 哪三个不同的线索与食欲的结果(糖丸奖励)、厌恶的结果 结果(轻度足部电击)，或无结果。在学习之后，食欲和厌恶的结果会逆转这种情况 以前与电击配对的线索将先于奖励传递，反之亦然。我会接受训练的 纤维光度法记录VTA、多巴胺和GABA神经元以及化学发生操作 MPFC-VTA途径的研究，以测试mPFC是否以价特定的方式调节灵活的更新。 无论结果如何，拟议的工作都将增加我们对灵活更新 当结果意外情况发生变化时的行为反应。

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.