Sex differences in the neurophysiology of the olfactory system

嗅觉系统神经生理学的性别差异

基本信息

批准号：
8803006
负责人：
John P McGann
金额：
$ 10万
依托单位：
RUTGERS, THE STATE UNIV OF N.J.
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-01 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8803006
关键词：
Address Affect American Animals Behavioral Biological Models Brain Brain region Calcium Calcium Signaling Censuses Clinical Treatment Cognition Cognitive Cues Data Development Discrimination Disease Dyes Environment Esthesia Exocytosis Fiber Image Imagery Imaging Techniques Information Theory Learning Literature Mediating Methods Modeling Mus Nature Nerve Nervous system structure Neurons Odors Olfactory Nerve Olfactory Receptor Neurons Organ Outcome Output Pathway interactions Patients Pattern Perception Physiological Placebo Effect Play Presynaptic Terminals Process Prosthesis Psychophysics Research Response Latencies Role Sensory Sensory Disorders Sensory Process Sex Characteristics Shapes Signal Transduction Smell Perception Speed Stimulus Synapses System Techniques Testing Therapeutic Time Training Transgenic Mice Wild Type Mouse Work awake base design expectation experience improved in vivo insight neuromechanism neurophysiology neurotransmitter release olfactory bulb olfactory stimulus optical imaging presynaptic public health relevance receptor relating to nervous system research study response sensor sensory cortex sensory system spatiotemporal theories

项目摘要

DESCRIPTION (provided by applicant): A growing body of scientific literature indicates that sensory processing in the nervous system incorporates not just "bottom-up" analysis of sensory information that originates from the sensory organs but also "top-down" expectations about the organization of the sensory world that derive from previous sensory experience. In the olfactory system the first convergence of bottom-up and top-down projections occurs in the glomeruli of the olfactory bulb, where optical imaging techniques now permit the visualization of presynaptic calcium signaling and neurotransmitter release from olfactory receptor neurons (the very first neurons in the olfactory system) in awake mice that are smelling odors and learning about their environment. The olfactory system is thus a uniquely powerful model system to study the synthesis of top-down and bottom-up information. Remarkably, in preliminary experiments we have found that this primary sensory input is strongly modulated by the mouse's expectations about olfactory stimuli, as established by prior sensory experience during the imaging session. For instance, if an odor is always presented after a "warning tone" cue, the unexpected presentation of that odor without the tone evokes much less presynaptic calcium influx and less neurotransmitter release from the olfactory nerve than when the odor follows the cue. This effect appears to occur via a GABAB receptor-mediated presynaptic inhibition of neurotransmitter release from these synapses. Because the output of the receptor neurons themselves is modulated by expectations, these data suggest that there is actually no purely bottom-up information in the olfactory system at all. This has profound implications for our understanding of neural representations of olfactory stimuli and will inform our understanding of other, less experimentally tractable sensory systems. This proposal confirms and extends these findings by testing the nature of the expectations (e.g. is the expectation odor-specific?), their time course (e.g. are expectation effects anticipatory?), and their neural mechanisms (e.g. are descending projections to the olfactory bulb necessary during the establishment of the expectation or only for detecting unexpected outcomes?). Further experimentation is designed to reveal the perceptual consequences of these neural changes (e.g. do expected odors smell stronger than unexpected odors?) and whether the difference in neurotransmitter release from receptor neurons is necessary for these perceptual effects to occur. Importantly, this work will be designed and analyzed in the context of information theory, a formal theory that allows the quantification of how expected or surprising a given stimulus is and thus provides testable quantitative predictions for assessing the neurophysiological and psychophysical consequences of expectation. These results should provide an essential step in understanding how cognition can play a role in perception as early as the first neurons in a sensory system.

描述（由申请人提供）：越来越多的科学文献表明，神经系统中的感官处理不仅包含源自感官器官的感觉信息的“自下而上”分析，而且还包括对感官组织的“自上而下”的期望，这些期望是从先前的感官体验中获得的。在嗅觉系统中，自下而上和自上而下的投影的第一个融合发生在嗅球的肾小球中，现在，光学成像技术允许可视化突触前钙信号传导和神经递质从嗅觉受体神经元中释放出来（在嗅觉系统中的最初神经元）中的环境中，这是在嗅觉系统中的奇异味。因此，嗅觉系统是研究自上而下和自下而上信息的综合的独特强大模型系统。值得注意的是，在初步实验中，我们发现这种主要的感觉输入受小鼠对嗅觉刺激的期望强烈调节，这是由成像过程中的先前感觉体验确定的。例如，如果在“警告音”提示后始终出现气味，那么没有这种气味的气味出现的出乎意料的表现会引起嗅觉神经的突触前钙的涌入，而神经递质的神经递质却少于嗅觉的神经递质，而不是当气味跟随提示时。这种作用似乎是通过GABAB受体介导的突触前抑制神经递质从这些突触中释放出来的。由于受体神经元本身的输出受期望调节，因此这些数据表明，嗅觉系统中实际上根本没有纯粹的自下而上信息。这对我们对我们的理解具有深远的影响嗅觉刺激的神经表示，并将告知我们对其他实验性的感觉系统的理解。该提案通过测试期望的性质（例如，期望特定的？），它们的时间课程（例如，期望效果是否期待？）及其神经机制（例如，在建立期望或仅在探测意外的淘汰期间，对嗅觉的预期期间必要的预期降低预测，是期望的效果吗？）。进一步的实验旨在揭示这些神经变化的感知后果（例如，预期气味闻起来比意外气味更强烈吗？），是否需要从受体神经元中释放神经递质的差异才能发生这些感知作用。重要的是，这项工作将在信息理论的背景下进行设计和分析，这是一种正式理论，允许量化给定刺激的期望或令人惊讶，因此提供了可测试的定量预测，以评估预期的神经生理学和心理物理学后果。这些结果应该为了解认知如何早在感官系统中的第一个神经元中发挥作用而提供一个重要的步骤。