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Identification of the ligands and sensory neurons that mediate pheromone behavior

介导信息素行为的配体和感觉神经元的鉴定

基本信息

批准号：
8213699
负责人：
LISA STOWERS
金额：
$ 38.67万
依托单位：
SCRIPPS RESEARCH INSTITUTE, THE
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-02-01 至 2014-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8213699
关键词：
Adult Afferent Neurons Affinity Chromatography Age Aggressive behavior American Amygdaloid structure Animals Behavior Behavioral Behavioral Paradigm Biochemical Biochemistry Brain Calcium Cell Nucleus Cells Chemicals Chemistry Code Complement Complex Ensure Environment Female Functional disorder Funding Gender Genetic Goals Hand Health Histocytochemistry Human Hypothalamic structure Image Immunohistochemistry In Situ Hybridization Individual Instinct Investigation Knowledge Laboratories Lead Learning Ligands Link Logic Medial Mediating Memory Methods Modeling Molecular Molecular Analysis Molecular Genetics Molecular Profiling Mus Neural Pathways Neurons Neurophysiology - biologic function Neurosecretory Systems Olfactory Epithelium Outcome Partner in relationship Pathway interactions Pattern Pharmaceutical Preparations Pheromone Plastics Population Positioning Attribute Regulation Reporter Research Research Institute Rodent Signal Transduction Social Behavior Societies Stimulus Swab System Techniques Testing Therapeutic Therapeutic Intervention Urine base behavior test design experience male mutant neural circuit neural information processing neuromechanism novel receptor relating to nervous system research study response small molecule social tool

项目摘要

DESCRIPTION (provided by applicant): Neural information processing utilizes an unfathomable number of discrete circuits composed of seemingly similar neurons dedicated to specific and diverse tasks. Elucidation of the temporal activity, spatial organization, or molecular differences among neurons that lead to distinct perceptual, neuroendocrine, or behavioral outcomes is critical to the design of effective therapeutic intervention. The molecular-genetics revolution of the investigation of chemosensory-mediated behavior has provided the potential to identify, manipulate, and reveal the mechanisms that underlie individual neural circuits. Though great progress has been made in identifying groups of receptors and neurons that participate in chemosensory information coding we do not know the specific ligands and neural circuits that mediate any defined behavior in a mammalian model. The objective of this research is to identify the pheromone ligands, responding sensory neurons, and necessary neuronal circuits that mediate a specific social behavior in the mouse. 1) We will use a novel chemical capture method to chemically tag, enrich, and profile small molecules of any physicochemical class to identify the specific pheromones that encode a single defined behavior. 2) We expect that an individual behavior is mediated by a dedicated subset of chemosensory neurons. We will use calcium imaging combined with molecular and histochemical methods to define the sensory neurons that promote the behavior. 3) Social behavior in rodents is plastic; the age and gender of the receiving animal determines whether it will respond. We predict that neuronal pathways that are active in responding animals are inactive, not present, or spatially distinct from those activated in non-responding animals. We will analyze mice expressing a novel genetic reporter of cFos activation to define and manipulate the neural circuit underlying a single behavior. We expect that at the completion of these aims we will have made an important first step that will allow us to predictably activate social behavior in mice and therefore define at the cellular and molecular level underlying mechanisms of neural function and dysfunction. PUBLIC HEALTH RELEVANCE In the mouse, sensory neurons that respond to pheromones activate nuclei in the medial amygdala and hypothalamus. These same nuclei have been implicated in regulating social behavior in humans. However, elucidation of the organization, functional significance, and specific mechanism of action of these centers is impeded by the lack of knowledge of the corresponding function of subsets of amygdala and hypothalamic neurons. We are defining components of the signals that elicit and regulate a known behavior. This important first step will allow us to predictably activate social responses in mice, and therefore define at the cellular and molecular level, the underlying mechanisms of neural function and dysfunction.

描述（由申请人提供）：神经信息处理利用由看似相似的神经元组成的不可估量数量的离散电路，这些神经元专用于特定和不同的任务。阐明导致不同感知、神经内分泌或行为结果的神经元之间的时间活动、空间组织或分子差异对于设计有效的治疗干预至关重要。化学感觉介导行为研究的分子遗传学革命为识别、操纵和揭示个体神经回路的机制提供了可能。虽然在识别参与化学感受信息编码的受体和神经元组方面取得了很大进展，但我们不知道在哺乳动物模型中介导任何定义行为的特定配体和神经回路。本研究的目的是确定信息素配体，反应的感觉神经元，和必要的神经元回路，介导一个特定的社会行为的小鼠。1)我们将使用一种新的化学捕获方法来化学标记，丰富和配置文件的任何物理化学类的小分子，以确定编码一个单一的定义行为的特定信息素。2)我们期望个体行为是由化学感觉神经元的专用子集介导的。我们将使用钙成像结合分子和组织化学方法来确定促进行为的感觉神经元。3)啮齿类动物的社会行为是可塑性的;接受动物的年龄和性别决定了它是否会做出反应。我们预测，在响应动物中活跃的神经元通路是不活跃的，不存在的，或空间上不同于那些在非响应动物中激活的。我们将分析表达cFos激活的新型遗传报告基因的小鼠，以定义和操纵单一行为背后的神经回路。我们希望在完成这些目标时，我们将迈出重要的第一步，使我们能够可预测地激活小鼠的社会行为，从而在细胞和分子水平上确定神经功能和功能障碍的潜在机制。在老鼠体内，对信息素有反应的感觉神经元激活内侧杏仁核和下丘脑的核团。这些核团也参与了人类社会行为的调节。然而，阐明这些中心的组织，功能意义和具体的作用机制是阻碍了杏仁核和下丘脑神经元的子集的相应功能的知识缺乏。我们正在定义引发和调节已知行为的信号组件。这重要的第一步将使我们能够可预测地激活小鼠的社会反应，从而在细胞和分子水平上定义神经功能和功能障碍的潜在机制。