Cognitive modulation of primary sensory processing in olfactory receptor neurons

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来自感觉器官的“自下而上”的感觉信息分析，还包括来自先前感觉经验的“自上而下”的对感觉世界组织的期望。在嗅觉系统中，自下而上和自上而下的投影的第一次汇聚发生在嗅球的肾小球中，在那里，光学成像技术现在允许可视化突触前钙信号和嗅觉受体神经元（嗅觉系统中最早的神经元）释放的神经递质，这些神经元在清醒的小鼠中闻到气味并了解他们的环境。因此，嗅觉系统是研究自上而下和自下而上信息综合的独特强大的模型系统。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到小鼠对嗅觉刺激的预期的强烈调节，正如在成像过程中通过先前的感觉经验所建立的那样。例如，如果一种气味总是在“警告音调”提示之后出现，那么没有音调的气味的意外呈现会比气味跟随提示时引起的突触前钙流入和嗅觉神经释放的神经递质少得多。这种效应似乎是通过GABAB受体介导的突触前神经递质释放抑制而发生的。因为受体神经元本身的输出是由预期调节的，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的信息。这对我们理解

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.