Dissecting the Neural Circuits Encoding Positive and Negative Valence

描述（由申请人提供）：两种主要的情绪或动机效价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，这种能力的扰动可能导致与精神疾病相关的异常行为。众所周知，杏仁核是处理动机效价的关键区域，但神经科学的一个基本问题是：相反的行为输出如何由类似的神经机制调节？一种可能的解释是，积极或消极动机效价的处理过程在很大程度上分裂成不同的回路。过去十年的电生理记录研究提供了令人信服的证据，证明杏仁核可能是这个最初的分歧点。然而，这一假设尚未得到直接验证。在这里，我们建议直接验证正负价加工在基底外侧杏仁核发生分歧的假设，这一假设同时投射到恐惧和奖励回路。我们将测试下游投射目标是否在先天和习得关联中定义了这些不同的群体，探索神经活动和突触可塑性是否优先发生在投射定义的神经群体中，并确定恐惧和奖励回路中的新目标。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特定神经投射和行为之间因果关系的特定假设的可行性，描述了细胞和突触机制，并扩展了我们目前对动机电路的了解。具体来说，这位研究者在投射特异性光遗传学操作，电生理学，免疫组织化学和药理学操作方面拥有广泛的专业知识，以研究动机行为的神经基础。本研究的成功成果将在理解正效价和负效价的神经基础方面取得重大的概念进展。

DESCRIPTION (provided by applicant): 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 aberrat 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-speciic 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.