A Sensory Map for Sulfated Steroids in the Accessory Olfactory Bulb

附件嗅球中硫酸类固醇的感觉图

• 批准号: 8263415
• 负责人: Gary Hammen
• 金额: $ 4.38万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8263415
• 关键词: AVPR2 gene; Accessory Olfactory Bulbs; Afferent Neurons; Aggressive behavior; Animals; Anterior; Axon; Behavior; Behavioral; Calcium; Cells; Chemicals; Complex; Corticosterone; Coupled; Dependence; Development; Environment; Estradiol; Estrogens; Excitatory Synapse; Family; Female; Fluorescence; GABA-B Receptor; Gender; Goals; Individual; Inorganic Sulfates; Interneurons; Lateral; Ligands; Liquid substance; Maps; Measurable; Measures; Mediating; Memory; Microscopy; Modeling; Nasal cavity; Nature; Neurites; Neurons; Neuropil; Neurosecretory Systems; Nose; Odors; Optics; Output; Partner in relationship; Pattern; Perception; Phase; Physiological; Population; Preparation; Presynaptic Terminals; Progesterone; Relative (related person); Reproduction; Research; Response to stimulus physiology; Role; Sensory; Sensory Process; Shapes; Signal Transduction; Site; Social Interaction; Spatial Distribution; Specificity; Stereotyping; Steroids; Stimulus; Stress; Structure; Sum; Synapses; System; Testing; Testosterone; Unspecified or Sulfate Ion Sulfates; Urine; base; calcium indicator; design; environmental chemical; estrogen sulfate; gamma-Aminobutyric Acid; male; neural circuit; neurotransmission; olfactory bulb; presynaptic; public health relevance; receptor; research study; response; segregation; sex; steroid sulfate; vomeronasal organ

DESCRIPTION (provided by applicant): In this proposal we describe a set of experiment designed to test how sensory signals are represented at the first synapse of the accessory olfactory system. The accessory olfactory system detects chemical signals pertinent to behavioral responses ranging from aggression to neuroendocrine control of reproduction in animals. Sensory neurons in the nose project to the accessory olfactory bulb, where axons from neurons expressing the same receptor type co-converge on small regions of neuropil called glomeruli. Individual receptor types converge within subsets of glomeruli in a single lamina of the laminar accessory olfactory bulb. Within these glomeruli, sensory neurons synapse on mitral cells, which encode sensory signals and project out of the olfactory bulb. It is unknown whether the response patterns of the sensory neurons and mitral cells have a spatial correlate in the glomeruli. In addition to connections with mitral cells, sensory neurons drive activity in glomerular inhibitory interneurons. GABA(A) and (B) receptors are expressed both pre- and post-synaptically; these inhibitory receptors are candidate effectors for a variety of circuit and sensory processing tasks from scaling and normalization of inputs to the encoding of specific memories for the scent of other animals. However, virtually nothing is known about the degree to which inhibition shapes responses within the glomeruli. For example, it is unknown whether the inhibition is "lateral" (meaning, it acts between glomeruli corresponding to different receptors), and what the consequences of inhibition are for the output neurons of the bulb, the mitral cells. To examine the specificity of glomerular activation and mechanisms of inhibition, we will exploit the fact that the levels of signaling in sensory neuron terminals within the glomeruli are optically measurable as changes in calcium concentration, thus rendering the entire population response to a stimulus amenable to optical recording. In Aim 1, we will identify the spatial patterns of glomerular activation within the accessory olfactory bulb using sulfated steroids known to drive activity in both sensory neurons and mitral cells. We predict that glomerular activations by different ligands will be functionally separate and have stereotyped spatial distributions. In Aim 2, we will determine the role of inhibitory neurotransmission in shaping the responses of co-activated glomeruli. Populations of glomeruli will be identified by responses to individual sulfated steroids, and then the inhibitory interactions will be measured when the populations are simultaneously activated. The role of both GABA(A) and GABA(B) receptors will be measured, via GABA(A) and (B) antagonism. We predict that GABAergic inhibition of sensory neuron pre-synaptic terminals will occur both within glomeruli and between adjacent co-active glomeruli. If successful, these experiments will provide a mechanistic basis for recent observations such as diminished estrogen sulfate responsiveness of mitral cells relative to sensory neurons and sex-specific odor opponency. PUBLIC HEALTH RELEVANCE: The goal of the research plan presented in this proposal is to understand the how the accessory olfactory system detects and represents chemical signals in the environment. Specifically, this study will characterize both the spatial organization of chemosensory neuron response patterns and the role of inhibition in shaping complex stimulus response patterns in the accessory olfactory bulb glomeruli. These studies in the accessory olfactory system will record functional information from all sensory neurons in the accessory olfactory system, providing a broad perspective from which to form hypotheses about sensory processing.

描述（由申请人提供）：在本提案中，我们描述了一组实验，旨在测试感觉信号是如何在辅助嗅觉系统的第一个突触表示。辅助嗅觉系统检测与行为反应有关的化学信号，从动物的攻击性到生殖的神经内分泌控制。鼻子中的感觉神经元投射到副嗅球，在那里，来自表达相同受体类型的神经元的轴突共同聚集在称为肾小球的神经元的小区域上。个别受体类型收敛在肾小球的一个单一的层状副嗅球的子集。在这些肾小球内，感觉神经元与僧帽细胞形成突触，僧帽细胞编码感觉信号并伸出嗅球。尚不清楚感觉神经元和二尖瓣细胞的反应模式是否在肾小球中具有空间相关性。除了与二尖瓣细胞的连接，感觉神经元驱动肾小球抑制性中间神经元的活动。GABA（A）和（B）受体在突触前和突触后表达;这些抑制性受体是各种回路和感觉处理任务的候选效应物，从输入的缩放和标准化到对其他动物气味的特定记忆的编码。然而，几乎没有什么是已知的程度，抑制形状的反应在肾小球内。例如，目前还不清楚这种抑制是否是“横向的”（也就是说，它作用于与不同受体相对应的肾小球之间），以及抑制对球的输出神经元（二尖瓣细胞）的影响。 为了研究肾小球激活的特异性和抑制机制，我们将利用这样一个事实，即肾小球内感觉神经元末梢的信号传导水平可以作为钙浓度的变化进行光学测量，从而使整个人群对刺激的反应可以进行光学记录。在目标1中，我们将确定使用已知驱动感觉神经元和二尖瓣细胞活动的硫酸化类固醇的副嗅球内肾小球激活的空间模式。我们预测，肾小球激活不同的配体将在功能上分开，并有定型的空间分布。在目标2中，我们将确定抑制性神经传递在形成共激活肾小球反应中的作用。肾小球群体将通过对单个硫酸化类固醇的反应来识别，然后当群体同时激活时，将测量抑制相互作用。将通过GABA（A）和（B）拮抗作用测量GABA（A）和GABA（B）受体的作用。我们预测，GABA能抑制感觉神经元突触前末梢将发生在肾小球内和相邻的共同活动的肾小球之间。如果成功的话，这些实验将为最近的观察，如减少雌激素硫酸盐反应的二尖瓣细胞相对于感觉神经元和性别特异性的气味抑制提供一个机制的基础。 公共卫生关系：本提案中提出的研究计划的目标是了解辅助嗅觉系统如何检测和表示环境中的化学信号。具体而言，本研究将表征化学感觉神经元反应模式的空间组织和抑制在辅助嗅球肾小球中形成复杂刺激反应模式的作用。这些研究在辅助嗅觉系统将记录功能的信息，从所有的感觉神经元在辅助嗅觉系统，提供了一个广阔的视角，从形成假说的感觉处理。