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：
7763175
负责人：
LISA STOWERS
金额：
$ 39.95万
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/7763175
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 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 public health relevance 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）：神经信息处理利用了一个不可思议的离散电路，由看似相似的神经元组成，这些神经元专门针对特定和多样化的任务。神经元之间的时间活动，空间组织或分子差异阐明导致独特的感知，神经内分泌或行为结局对有效的治疗干预设计至关重要。化学感应介导的行为研究的分子基因革命提供了识别，操纵和揭示基于个体神经回路的机制的潜力。尽管在识别参与化学感觉信息编码的受体和神经元组方面取得了长足进展，但我们不知道介导哺乳动物模型中任何确定行为的特定配体和神经回路。这项研究的目的是识别信息素配体，反应感觉神经元以及介导小鼠中特定社会行为的必要神经元回路。 1）我们将使用一种新颖的化学捕获方法来化学标记，丰富和剖面的任何物理化学类别的小分子，以识别编码单个定义行为的特定信息素。 2）我们期望单个行为是由化学感应神经元的专用子集介导的。我们将使用结合分子和组织化学方法的钙成像来定义促进行为的感觉神经元。 3）啮齿动物的社会行为是塑料的；接收动物的年龄和性别决定了它是否会做出反应。我们预测，活性动物的神经元途径是不活跃的，没有存在的，或在空间上与非反应动物激活的神经途径不同。我们将分析表达新型遗传报道的小鼠CFO激活，以定义和操纵单个行为的神经回路。我们预计，在完成这些目标时，我们将做出一个重要的第一步，这将使我们可以预测地激活小鼠的社会行为，因此在神经功能和功能障碍的基础机制下定义了细胞和分子水平。公共卫生在小鼠中的相关性，对信息素反应的感觉神经元激活了杏仁核和下丘脑中的核。这些核与调节人类的社会行为有关。然而，由于缺乏对杏仁核和下丘脑神经元子集的相应功能的了解，这些中心的功能意义以及这些中心的特定作用机理的阐明，功能意义和特定的作用机理。我们正在定义引起和调节已知行为的信号的组成部分。这一重要的第一步将使我们可以预测地激活小鼠的社会反应，因此在细胞和分子水平上定义了神经功能和功能障碍的潜在机制。