Dissecting the Neural Circuits Encoding Positive and Negative Valence

项目摘要/摘要： 情感或动机价值的两个主要类别是寻求快乐和逃避 疼痛。辨别“好的”和“坏的”环境线索的能力对生存至关重要， 这种能力的紊乱可能会导致与精神疾病相关的异常行为。 虽然已知杏仁核是处理动机价态的关键区域，但 神经科学中的基本问题是：相反的行为输出如何通过 一种类似的神经机制？一种可能的可能性是，积极或消极的处理 动机价态出现分歧，形成大体不同的回路。电生理学 过去十年的记录研究提供了令人信服的证据，证明杏仁核可以起作用 作为这个最初的分歧点。然而，这一假设尚未得到直接检验。在这里，我们 建议直接检验正价和负价加工在 杏仁基底外侧核，投射到恐惧和奖赏回路。我们将测试 下游预测目标是否定义了先天和后天不同的种群 学习联想，探索神经活动和突触可塑性是否正在发生 优先在投射定义的神经群体中，并在恐惧和 奖赏线路。我们令人信服的初步数据集证明了应用 多种尖端技术来测试关于因果关系的特定假设 特定神经投射和行为之间的关系，表征细胞和 突触机制，并扩展了我们目前对动机回路的知识。 具体地说，这位研究人员在投影特定的光遗传学方面拥有丰富的专业知识 手法、电生理学、免疫组织化学和药物疗法 研究动机行为的神经基础。拟议研究的成功结果 将在理解积极和积极的神经基础方面取得重大的概念性进展 负价态。

Project Summary/Abstract: The two primary classes of emotional or motivational valence are seeking pleasure and avoiding pain. The ability to distinguish "good" and "bad" environmental cues is critical for survival, and perturbations in this ability can result in aberrant behaviors relevant to psychiatric disease. While the amygdala is known to be a region critical for processing motivational valence, a fundamental question in neuroscience is: How can opposing behavioral outputs be mediated by a similar neural mechanism? One likely possibility is that the processing of positive or negative motivation valence occurs with divergence into largely distinct circuits. Electrophysiological recording studies from the last decade provide compelling evidence that the amygdala could act as this initial divergence point. However, this hypothesis has not been directly tested. Here, we propose to directly test the hypothesis that positive and negative valence processing diverges at the basolateral amygdala, which projects to both the fear and reward circuits. We will test whether downstream projection targets define these different populations in both innate and learned associations, explore whether neural activity and synaptic plasticity are occurring preferentially in projection-defined neural populations, and identify novel targets in the fear and reward circuits. Our compelling preliminary data sets demonstrate the feasibility of applying multiple cutting-edge techniques to testing the specific hypotheses regarding causal relationships between specific neural projections and behavior, characterizing the cellular and synaptic mechanisms, and expanding our current knowledge of motivational circuitry. Specifically, this investigator has extensive expertise in projection-specific optogenetic manipulations, electrophysiology, immunohistochemistry and pharmacological manipulations to study the neural basis of motivated behaviors. A successful outcome of the proposed research will establish a major conceptual advance in understanding the neural basis of positive and negative valence.