Department of Neurobiology, University of Utah School of Medicine, Salt Lake City, United States.
Biocomputation Group, Centre of Data Innovation Research, Department of Computer Science, University of Hertfordshire, Hertfordshire, United Kingdom.
Elife. 2022 Jul 21;11:e80470. doi: 10.7554/eLife.80470.
In olfactory systems, convergence of sensory neurons onto glomeruli generates a map of odorant receptor identity. How glomerular maps relate to sensory space remains unclear. We sought to better characterize this relationship in the mouse olfactory system by defining glomeruli in terms of the odorants to which they are most sensitive. Using high-throughput odorant delivery and ultrasensitive imaging of sensory inputs, we imaged responses to 185 odorants presented at concentrations determined to activate only one or a few glomeruli across the dorsal olfactory bulb. The resulting datasets defined the tuning properties of glomeruli - and, by inference, their cognate odorant receptors - in a low-concentration regime, and yielded consensus maps of glomerular sensitivity across a wide range of chemical space. Glomeruli were extremely narrowly tuned, with ~25% responding to only one odorant, and extremely sensitive, responding to their effective odorants at sub-picomolar to nanomolar concentrations. Such narrow tuning in this concentration regime allowed for reliable functional identification of many glomeruli based on a single diagnostic odorant. At the same time, the response spectra of glomeruli responding to multiple odorants was best predicted by straightforward odorant structural features, and glomeruli sensitive to distinct odorants with common structural features were spatially clustered. These results define an underlying structure to the primary representation of sensory space by the mouse olfactory system.
在嗅觉系统中,感觉神经元汇聚到嗅小球上,形成了气味受体身份的图谱。然而,嗅小球图谱与感觉空间的关系尚不清楚。我们试图通过定义对最敏感的气味分子具有反应的嗅小球,来更好地描述小鼠嗅觉系统中这种关系。我们使用高通量气味传递和对感觉输入的超高灵敏度成像,对 185 种气味分子进行成像,这些气味分子的浓度被确定为只能激活背侧嗅球中一个或几个嗅小球。由此产生的数据集定义了嗅小球——以及它们的同源气味受体——在低浓度条件下的调谐特性,并得出了在广泛的化学空间中,嗅小球敏感性的共识图谱。嗅小球的调谐非常狭窄,大约有 25%的嗅小球只对一种气味分子有反应,而且非常敏感,能在亚皮摩尔到纳摩尔浓度下对其有效气味分子产生反应。在这种浓度条件下,如此狭窄的调谐可以仅基于一种诊断性气味分子,对许多嗅小球进行可靠的功能鉴定。同时,对多种气味分子有反应的嗅小球的反应谱,最好由简单的气味分子结构特征来预测,而对具有共同结构特征的不同气味分子敏感的嗅小球在空间上是聚类的。这些结果定义了小鼠嗅觉系统对感觉空间的主要表示的基础结构。