Dissecting the Neural Circuits Encoding Positive and Negative Valence

剖析编码正价和负价的神经回路

• 批准号: 9184579
• 负责人: Kay Maxine Tye
• 金额: $ 39万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-15 至 2018-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9184579
• 关键词: Amygdaloid structure; Anatomy; Anxiety; Basic Science; Behavior; Behavioral; Behavioral Assay; Biological Assay; Brain; Cells; Complex; Conditioned Stimulus; Cues; Data; Data Set; Dyes; Electrophysiology (science); Emotional; Environment; Freezing; Fright; Gene Expression; Glutamates; Goals; Image; Imaging Device; Immediate-Early Genes; Immunohistochemistry; Interdisciplinary Study; Knowledge; Learning; Maps; Mediating; Memory; Mental Depression; Mental disorders; Motivation; Nature; Negative Valence; Neurons; Neurosciences; Outcome; Output; Pain; Pattern; Pharmacology; Population; Positive Valence; Presynaptic Terminals; Primates; Property; Recruitment Activity; Research; Research Personnel; Rewards; Rodent; Sensory; Shock; Site; Stimulus; Sucrose; Synapses; Synaptic plasticity; Techniques; Technology; Testing; Time; Work; addiction; anxiety-related behavior; base; brain morphology; classical conditioning; conditioned fear; conditioning; experimental study; hedonic; in vivo; innovation; insight; motivated behavior; neural circuit; neural patterning; neuromechanism; novel; optogenetics; patch clamp; pleasure; preference; programs; public health relevance; reconstruction; relating to nervous system; response; sensory input; sensory stimulus; tool

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.

描述（由申请人提供）：情感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”环境线索的能力对于生存至关重要，这种能力的干扰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，但神经科学的一个基本问题是：如何通过类似的神经机制介导相反的行为输出？一种可能的可能性是，积极或消极动机效价的处理发生在很大程度上不同的回路中。过去十年的电生理记录研究提供了令人信服的证据，证明杏仁核可以充当这个初始分歧点。然而，这一假设尚未得到直接检验。在这里，我们建议直接检验这样的假设：正价和负价处理在基底外侧杏仁核处出现分歧，该处理投射到恐惧和奖励回路。我们将测试下游投影目标是否在先天关联和学习关联中定义这些不同的群体，探索神经活动和突触可塑性是否优先发生在投影定义的神经群体中，并识别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有关特定神经投射和行为之间因果关系的特定假设、表征细胞和突触机制以及扩展我们当前对动机回路的知识的可行性。具体来说，该研究人员在投影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。拟议研究的成功结果将为理解正价和负价的神经基础奠定一个重大的概念进展。