Cognitive modulation of primary sensory processing in olfactory receptor neurons

嗅觉受体神经元初级感觉处理的认知调节

• 批准号: 8676775
• 负责人: John P McGann
• 金额: $ 38.75万
• 依托单位: RUTGERS, THE STATE UNIV OF N.J.
• 依托单位国家: 美国
• 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/8676775
• 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; 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

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，神经系统中的感觉处理不仅包括对源自感觉器官的感觉信息的“自下而上”分析，还包括对源自先前感觉经验的感觉世界的组织的“自上而下”预期。在嗅觉系统中，自下而上和自上而下投射的第一次会聚发生在嗅球的肾小球中，在那里，光学成像技术现在允许观察突触前钙信号和嗅觉受体神经元（嗅觉系统中的第一个神经元）释放的神经递质。嗅觉系统因此是一个独特的强大的模型系统，研究自上而下和自下而上的信息的合成。值得注意的是，在初步的实验中，我们发现，这种主要的感觉输入强烈调制的小鼠的嗅觉刺激的期望，建立在成像过程中的先前的感觉经验。例如，如果一种气味总是在“警告音”提示之后出现，那么与气味跟随提示时相比，在没有提示音的情况下，这种气味的意外出现引起的突触前钙流入和嗅觉神经释放的神经递质要少得多。这种效应似乎是通过GABAB受体介导的突触前抑制这些突触的神经递质释放而发生的。由于受体神经元的输出本身受到预期的调节，这些数据表明，嗅觉系统中实际上根本不存在纯粹的自下而上的信息。这对我们理解 嗅觉刺激的神经表征，并将告知我们对其他不太容易实验处理的感觉系统的理解。该提案通过测试期望的性质（例如，期望是特定于气味的吗？）来证实和扩展这些发现，它们的时间进程（例如，预期效应是否具有预期性？）以及它们的神经机制（例如，在建立预期过程中，向嗅球的下行投射是必要的，还是仅用于检测意外结果？）。进一步的实验旨在揭示这些神经变化的感知后果（例如，预期的气味比意外的气味闻起来更强烈吗？）以及受体神经元释放神经递质的差异是否是这些感知效应发生的必要条件。重要的是，这项工作将在信息论的背景下进行设计和分析，信息论是一种正式的理论，允许量化给定刺激的预期或令人惊讶的程度，从而为评估预期的神经生理和心理物理后果提供可测试的定量预测。这些结果应该为理解认知如何早在感觉系统的第一个神经元中就在感知中发挥作用提供了重要的一步。