Concentration tuning mediated by spare receptor capacity in olfactory sensory neurons: A theoretical study
Concentration tuning mediated by spare receptor capacity in olfactory sensory neurons: A theoretical study
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DOI：
10.1162/089976699300016188
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发表时间：
1999-10-01
影响因子：
2.9
通讯作者：
Linster, C
中科院分区：
文献类型：
--
作者：
Cleland, TA;Linster, C
嗅觉系统能够检测非常低浓度的气味。生理学实验已经证明，在来自感觉上皮的制剂中，气味敏感性低至皮摩尔范围。然而，嗅觉信号转导的当代模型提供了气味剂以相对低的特异性和因此低的亲和力结合到嗅觉受体，使得这种低浓度气味剂的检测在理论上难以理解。我们采用了一个计算模型，以证明如何嗅觉感觉神经元（OSN）的敏感性可以通过调节受体效应器耦合和/或其他机制调节备用受体容量调谐，从而解决这个难题。整个嗅球和突触后二尖瓣细胞的EC 10 -90强度调谐范围（ITRs）是相当广泛的比个别OSN的相应ITRs。这些数据是难以调和的某些当代的假设，收敛OSN在哺乳动物表现出一个均匀的人口的嗅觉受体和相同的调谐气味刺激。我们发现，在一个收敛的OSN群体中，备用受体容量的异质性可以增加一个收敛的OSN群体的ITR（EC 10 -90），而不管该群体中是否存在受体表达的多样性。在OSN中观察到受体-效应器偶联的调节;备用受体容量的细胞调节的其他机制也是高度合理的（例如，受体和效应蛋白的相对表达水平的定量调节）。我们提出了一个模型，说明这些过程可以成为OSN如何表现出高灵敏度的气味刺激，而不需要增加配体-受体结合亲和力或特异性，以及如何收敛的OSN的人口可以表现出更广泛的浓度敏感性比其个别组成的神经元，即使人口表达相同的气味受体。备用受体容量的调节可能在嗅觉系统可靠地检测低气味浓度、区分气味强度以及将该强度信息与气味质量的表征分离的能力中起重要作用。
The olfactory system is capable of detecting odorants at very low concentrations. Physiological experiments have demonstrated odorant sensitivities down to the picomolar range in preparations from the sensory epithelium. However, the contemporary model for olfactory signal transduction provides that odorants bind to olfactory receptors with relatively low specificity and consequently low affinity, making this detection of low-concentration odorants theoretically difficult to understand. We employ a computational model to demonstrate how olfactory sensory neuron (OSN) sensitivity can be tuned by modulation of receptor-effector coupling and/or by other mechanisms regulating spare receptor capacity, thus resolving this conundrum.The EC10-90 intensity tuning ranges (ITRs) of whole olfactory glomeruli and postsynaptic mitral cells are considerably broader than the commensurate ITRs of individual OSNs. These data are difficult to reconcile with certain contemporary hypotheses that convergent OSNs in mammals exhibit a homogeneous population of olfactory receptors and identical tuning for odor stimuli. We show that heterogeneity in spare receptor capacities within a convergent OSN population can increase the ITR (EC10-90) of a convergent population of OSNs regardless of the presence or absence of a diversity of receptor expression within the population.The modulation of receptor-effector coupling has been observed in OSNs; other mechanisms for cellular regulation of spare receptor capacity are also highly plausible (e.g., quantitative regulation of the relative expression levels of receptor and effector proteins). We present a model illustrating that these processes can underlie both how OSNs come to exhibit high sensitivity to odorant stimuli without necessitating increased ligand-receptor binding affinities or specificities and how a population of convergent OSNs could exhibit a broader concentration sensitivity than its individual constituent neurons, even given a population expressing identical odorant receptors. The regulation of spare receptor capacity may play an important role in the olfactory system's ability to reliably detect low odor concentrations, discriminate odor intensities, and segregate this intensity information from representations of odor quality.