Molecular Genetics Section, National Institute of Dental and Craniofacial Research/NIH, Bethesda, MD, USA.
Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
Mol Pain. 2021 Jan-Dec;17:17448069211013633. doi: 10.1177/17448069211013633.
Mouse behavioral assays have proven useful for the study of thermosensation, helping to identify receptors and circuits responsible for the transduction of thermal stimuli and information relay to the brain. However, these methods typically rely on observation of behavioral responses to various temperature stimuli to infer sensory ability and are often unable to disambiguate innocuous thermosensation from thermal nociception or to study thermosensory circuitry which do not produce easily detectable innate behavioral responses. Here we demonstrate a new testing apparatus capable of delivering small, rapid temperature change stimuli to the mouse's skin, permitting the use of operant conditioning to train mice to recognize and report temperature change. Using this assay, mice that were trained to detect a large temperature change were found to generalize this learning to distinguish much smaller temperature changes across the entire range of innocuous temperatures tested. Mice with ablated TRPV1 and TRPM8 neuronal populations had reduced ability to discriminate temperature differences in the warm (>35°C) and cool (<30°C) ranges, respectively. Furthermore, mice that were trained to recognize temperature changes in only the cool, TRPM8-mediated temperature range did not generalize this learning in the warm, TRPV1-mediated range (and vice versa), suggesting that thermosensory information from the TRPM8- and TRPV1-neuronal populations are perceptually distinct.
鼠类行为学检测已被证明在温度感知研究中具有重要作用,有助于识别感受温度刺激的受体和相关回路,并将温度信息传递到大脑。然而,这些方法通常依赖于观察对各种温度刺激的行为反应来推断感觉能力,并且往往无法区分无害的温度感知和热痛觉,或者无法研究不产生明显先天行为反应的温度感知回路。在这里,我们展示了一种新的测试设备,能够向小鼠皮肤传递小而快速的温度变化刺激,从而可以使用操作性条件作用来训练小鼠识别和报告温度变化。使用该检测方法,我们发现经过训练以检测大温度变化的小鼠能够将这种学习推广到整个无害温度范围内,以区分更小的温度变化。TRPV1 和 TRPM8 神经元群体缺失的小鼠在温暖(>35°C)和凉爽(<30°C)范围内区分温度差异的能力降低。此外,经过训练以识别仅在凉爽、TRPM8 介导的温度范围内的温度变化的小鼠,无法将这种学习推广到温暖、TRPV1 介导的温度范围内(反之亦然),这表明来自 TRPM8 和 TRPV1 神经元群体的温度感知信息在感知上是不同的。