Monell Chemical Senses Center, Philadelphia, PA, United States of America.
Department of Basic Medical Sciences, Neuroscience and Sensory Organs, University of Bari "A. Moro", Bari, Italy.
PLoS One. 2021 May 3;16(5):e0249798. doi: 10.1371/journal.pone.0249798. eCollection 2021.
Peripheral sensory cells and the central neuronal circuits that monitor environmental changes to drive behaviors should be adapted to match the behaviorally relevant kinetics of incoming stimuli, be it the detection of sound frequencies, the speed of moving objects or local temperature changes. Detection of odorants begins with the activation of olfactory receptor neurons in the nasal cavity following inhalation of air and airborne odorants carried therein. Thus, olfactory receptor neurons are stimulated in a rhythmic and repeated fashion that is determined by the breathing or sniffing frequency that can be controlled and altered by the animal. This raises the question of how the response kinetics of olfactory receptor neurons are matched to the imposed stimulation frequency and if, vice versa, the kinetics of olfactory receptor neuron responses determine the sniffing frequency. We addressed this question by using a mouse model that lacks the K+-dependent Na+/Ca2+ exchanger 4 (NCKX4), which results in markedly slowed response termination of olfactory receptor neuron responses and hence changes the temporal response kinetics of these neurons. We monitored sniffing behaviors of freely moving wildtype and NCKX4 knockout mice while they performed olfactory Go/NoGo discrimination tasks. Knockout mice performed with similar or, surprisingly, better accuracy compared to wildtype mice, but chose, depending on the task, different odorant sampling durations depending on the behavioral demands of the odorant identification task. Similarly, depending on the demands of the behavioral task, knockout mice displayed a lower basal breathing frequency prior to odorant sampling, a possible mechanism to increase the dynamic range for changes in sniffing frequency during odorant sampling. Overall, changes in sniffing behavior between wildtype and NCKX4 knockout mice were subtle, suggesting that, at least for the particular odorant-driven task we used, slowed response termination of the odorant-induced receptor neuron response either has a limited detrimental effect on odorant-driven behavior or mice are able to compensate via an as yet unknown mechanism.
外周感觉细胞和监测环境变化以驱动行为的中枢神经元回路应该适应与传入刺激的行为相关动力学相匹配，无论是检测声音频率、移动物体的速度还是局部温度变化。气味感受器的检测始于吸入空气和其中携带的空气传播气味后，鼻腔中嗅觉受体神经元的激活。因此，嗅觉受体神经元以由呼吸或嗅探频率决定的节律性和重复方式被刺激，而呼吸或嗅探频率可以被动物控制和改变。这就提出了一个问题，即嗅觉受体神经元的反应动力学如何与施加的刺激频率相匹配，以及反之，嗅觉受体神经元反应的动力学是否决定了嗅探频率。我们通过使用缺乏 K+-依赖性 Na+/Ca2+交换蛋白 4 (NCKX4) 的小鼠模型来解决这个问题，这导致嗅觉受体神经元反应的终止明显减慢，从而改变了这些神经元的时间反应动力学。我们在自由移动的野生型和 NCKX4 敲除小鼠执行嗅觉 Go/NoGo 辨别任务时监测它们的嗅探行为。与野生型小鼠相比，敲除小鼠的表现相似或出人意料地更好，但根据任务的不同，根据识别气味任务的行为需求，选择不同的气味采样持续时间。同样，根据行为任务的需求，敲除小鼠在气味采样前显示出较低的基础呼吸频率，这可能是增加嗅探频率变化动态范围的一种机制。总体而言，野生型和 NCKX4 敲除小鼠之间的嗅探行为变化很细微，这表明，至少对于我们使用的特定气味驱动任务，气味诱导的受体神经元反应终止速度减慢对气味驱动行为的不利影响有限，或者小鼠能够通过未知的机制进行补偿。
