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: 8413857
• 负责人: Gary Hammen
• 金额: $ 4.72万
• 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/8413857
• 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.

描述(申请人提供)：在这项提案中，我们描述了一组实验，旨在测试感觉信号如何在辅助嗅觉系统的第一个突触上表现出来。辅助嗅觉系统检测与动物从攻击到神经内分泌控制生殖等行为反应相关的化学信号。鼻子中的感觉神经元投射到副嗅球，在那里，表达相同受体类型的神经元的轴突共同汇聚在神经束的小区域，称为肾小球。单个受体类型汇聚在板层状副嗅球的单个板层内的肾小球亚群内。在这些肾小球内，感觉神经元与二尖瓣细胞突触，二尖瓣细胞编码感觉信号，并从嗅球投射出来。目前尚不清楚感觉神经元和二尖瓣细胞的反应模式在肾小球中是否存在空间相关性。除了与二尖瓣细胞的联系外，感觉神经元还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器，从调节和标准化输入到编码对其他动物气味的特定记忆。然而，关于抑制在多大程度上影响肾小球内的反应，我们几乎一无所知。例如，这种抑制是否是“侧向”的(即在对应于不同受体的肾小球之间起作用)，以及抑制对球的输出神经元--二尖瓣细胞--的影响尚不清楚。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终末的信号水平是可光学测量的，即钙浓度的变化，从而使整个群体对刺激的反应服从于光学记录。在目标1中，我们将使用硫酸盐类固醇确定副嗅球内肾小球激活的空间模式，已知的硫酸盐类固醇可驱动感觉神经元和二尖瓣细胞的活动。我们预测，不同配体对肾小球的激活在功能上是分开的，并具有刻板印象的空间分布。在目标2中，我们将确定抑制性神经传递在共同激活的肾小球反应中的作用。肾小球的群体将通过对单独的硫化类固醇的反应来识别，然后当群体同时被激活时，将测量抑制相互作用。将通过GABA(A)和(B)拮抗来测量GABA(A)和GABA(B)受体的作用。我们预测，感觉神经元突触前终末的GABA能抑制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，这些实验将为最近的观察提供机制基础，如二尖瓣细胞相对于感觉神经元的雌激素硫酸盐反应减弱，以及性别特异性气味对抗。