NS Pharma, Paramus, New Jersey.
AtlantiCare Regional Medical Center, Department of Family Medicine, Atlantic City, New Jersey.
J Neurophysiol. 2022 May 1;127(5):1317-1333. doi: 10.1152/jn.00544.2021. Epub 2022 Apr 7.
A defining feature of type I primary auditory afferents that compose ∼95% of the spiral ganglion is their intrinsic electrophysiological heterogeneity. This diversity is evident both between and within unitary, rapid, and slow adaptation (UA, RA, and SA) classes indicative of specializations designed to shape sensory receptor input. But to what end? Our initial impulse is to expect the opposite: that auditory afferents fire uniformly to represent acoustic stimuli with accuracy and high fidelity. Yet this is clearly not the case. One explanation for this neural signaling strategy is to coordinate a system in which differences between input stimuli are amplified. If this is correct, then stimulus disparity enhancements within the primary afferents should be transmitted seamlessly into auditory processing pathways that utilize population coding for difference detection. Using sound localization as an example, one would expect to observe separately regulated differences in intensity level compared with timing or spectral cues within a graded tonotopic distribution. This possibility was evaluated by examining the neuromodulatory effects of cAMP on immature neurons with high excitability and slow membrane kinetics. We found that electrophysiological correlates of intensity and timing were indeed independently regulated and tonotopically distributed, depending on intracellular cAMP signaling level. These observations, therefore, are indicative of a system in which differences between signaling elements of individual stimulus attributes are systematically amplified according to auditory processing constraints. Thus, dynamic heterogeneity mediated by cAMP in the spiral ganglion has the potential to enhance the representations of stimulus input disparities transmitted into higher level difference detection circuitry. Can changes in intracellular second messenger signaling within primary auditory afferents shift our perception of sound? Results presented herein lead to this conclusion. We found that intracellular cAMP signaling level systematically altered the kinetics and excitability of primary auditory afferents, exemplifying how dynamic heterogeneity can enhance differences between electrophysiological correlates of timing and intensity.
I 型初级听觉传入纤维的一个定义特征是其内在的电生理异质性，这些传入纤维构成了螺旋神经节的∼95%。这种多样性在单元、快速和缓慢适应（UA、RA 和 SA）类之间以及在这些类别内都很明显，表明存在专门化以塑造感觉受体输入。但目的是什么呢？我们最初的冲动是期望相反的结果：听觉传入纤维以均匀的方式发射，以准确和高保真的方式代表声音刺激。但事实显然并非如此。这种神经信号策略的一个解释是协调一个系统，在这个系统中，输入刺激之间的差异被放大。如果这是正确的，那么初级传入纤维中的刺激差异增强应该无缝地传递到利用群体编码进行差异检测的听觉处理途径中。以声音定位为例，人们期望在一个逐渐递增的音调分布中观察到强度水平与时间或频谱线索之间分别调节的差异。通过检查具有高兴奋性和慢膜动力学的未成熟神经元的 cAMP 对神经调制作用，我们评估了这种可能性。我们发现，强度和时间的电生理相关性确实是根据细胞内 cAMP 信号水平独立调节和音调分布的。因此，螺旋神经节中 cAMP 介导的电生理异质性是一种系统，根据听觉处理的限制，个体刺激属性的信号元件之间的差异被系统地放大。因此，初级听觉传入纤维中细胞内第二信使信号的变化有可能增强传入到更高水平差异检测电路的刺激输入差异的表示。细胞内第一级听觉传入纤维的第二信使信号变化会改变我们对声音的感知吗？本文提出的结果得出了这样的结论。我们发现细胞内 cAMP 信号水平系统地改变了初级听觉传入纤维的动力学和兴奋性，这说明了动态异质性如何增强时间和强度的电生理相关性之间的差异。
