Lubejko Susan T, Fontaine Bertrand, Soueidan Sara E, MacLeod Katrina M
Department of Biology, University of Maryland, College Park, Maryland.
Laboratory of Auditory Neurophysiology, University of Leuven, Leuven, Belgium.
J Neurophysiol. 2019 Dec 1;122(6):2576-2590. doi: 10.1152/jn.00234.2019. Epub 2019 Oct 2.
Single neurons function along a spectrum of neuronal operating modes whose properties determine how the output firing activity is generated from synaptic input. The auditory brain stem contains a diversity of neurons, from pure coincidence detectors to pure integrators and those with intermediate properties. We investigated how intrinsic spike initiation mechanisms regulate neuronal operating mode in the avian cochlear nucleus. Although the neurons in one division of the avian cochlear nucleus, nucleus magnocellularis, have been studied in depth, the spike threshold dynamics of the tonically firing neurons of a second division of cochlear nucleus, nucleus angularis (NA), remained unexplained. The input-output functions of tonically firing NA neurons were interrogated with directly injected in vivo-like current stimuli during whole cell patch-clamp recordings in vitro. Increasing the amplitude of the noise fluctuations in the current stimulus enhanced the firing rates in one subset of tonically firing neurons ("differentiators") but not another ("integrators"). We found that spike thresholds showed significantly greater adaptation and variability in the differentiator neurons. A leaky integrate-and-fire neuronal model with an adaptive spike initiation process derived from sodium channel dynamics was fit to the firing responses and could recapitulate >80% of the precise temporal firing across a range of fluctuation and mean current levels. Greater threshold adaptation explained the frequency-current curve changes due to a hyperpolarized shift in the effective adaptation voltage range and longer-lasting threshold adaptation in differentiators. The fine-tuning of the intrinsic properties of different NA neurons suggests they may have specialized roles in spectrotemporal processing. Avian cochlear nucleus angularis (NA) neurons are responsible for encoding sound intensity for sound localization and spectrotemporal processing. An adaptive spike threshold mechanism fine-tunes a subset of repetitive-spiking neurons in NA to confer coincidence detector-like properties. A model based on sodium channel inactivation properties reproduced the activity via a hyperpolarized shift in adaptation conferring fluctuation sensitivity.
单个神经元沿着一系列神经元运作模式发挥功能，这些模式的特性决定了突触输入如何产生输出放电活动。听觉脑干包含多种神经元，从纯粹的巧合探测器到纯粹的积分器以及具有中间特性的神经元。我们研究了内在的动作电位起始机制如何调节鸟类耳蜗核中的神经元运作模式。尽管对鸟类耳蜗核的一个分区——巨细胞核中的神经元已经进行了深入研究，但耳蜗核的另一个分区——角状核（NA）中持续放电神经元的动作电位阈值动态仍未得到解释。在体外全细胞膜片钳记录过程中，通过直接注入类似体内的电流刺激来研究持续放电的NA神经元的输入-输出功能。增加电流刺激中噪声波动的幅度会提高一部分持续放电神经元（“微分器”）的放电率，但不会提高另一部分（“积分器”）的放电率。我们发现，微分器神经元的动作电位阈值表现出明显更大的适应性和变异性。一个具有源自钠通道动力学的适应性动作电位起始过程的漏电整合-发放神经元模型与放电反应相拟合，并且可以在一系列波动和平均电流水平上概括超过80%的精确时间放电。更大的阈值适应性解释了由于有效适应电压范围的超极化偏移和微分器中持续时间更长的阈值适应性导致的频率-电流曲线变化。不同NA神经元内在特性的微调表明它们可能在频谱时间处理中具有特殊作用。鸟类耳蜗核角状核（NA）神经元负责对声音强度进行编码，以用于声音定位和频谱时间处理。一种适应性动作电位阈值机制对NA中一部分重复放电神经元进行微调，以赋予类似巧合探测器的特性。一个基于钠通道失活特性的模型通过适应性的超极化偏移赋予波动敏感性来再现活动。
