Dissecting the Neural Circuits Encoding Positive and Negative Valence

项目概要/摘要： 情绪或动机效价的两个主要类别是寻求快乐和避免 痛苦区分“好”和“坏”环境线索的能力对生存至关重要， 这种能力的紊乱可能导致与精神疾病相关的异常行为。 虽然杏仁核被认为是处理动机效价的关键区域， 神经科学的一个基本问题是： 类似的神经机制一个可能的可能性是，积极或消极的处理 动机效价的出现与分化成很大程度上不同的电路。电生理 过去十年的研究记录提供了令人信服的证据， 作为最初的分歧点。然而，这一假设尚未得到直接检验。这里我们 我建议直接检验这一假设，即积极和消极的效价加工在 基底外侧杏仁核，它投射到恐惧和奖励回路。我们将测试 下游投射靶是否在先天和先天两个方面定义了这些不同的群体， 学习关联，探索神经活动和突触可塑性是否正在发生 优先在投影定义的神经群体，并确定新的目标，在恐惧和 奖励电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有关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，并扩大我们目前的知识激励电路。 具体而言，该研究者在投射特异性光遗传学方面具有广泛的专业知识， 操作、电生理学、免疫组织化学和药理学操作， 研究动机行为的神经基础。拟议研究的成功结果 将建立一个重大的概念进步，在理解积极的神经基础， 负原子价

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.