Goldwyn Joshua H, McLaughlin Myles, Verschooten Eric, Joris Philip X, Rinzel John
Department of Mathematics, Ohio State University, Columbus, Ohio 43210,
Laboratory of Auditory Neurophysiology, Medical School, Campus Gasthuisberg, University of Leuven, B-3000 Leuven, Belgium.
J Neurosci. 2017 Oct 25;37(43):10451-10467. doi: 10.1523/JNEUROSCI.0600-17.2017. Epub 2017 Sep 25.
Extracellular voltage recordings ( ; field potentials) provide an accessible view of neural activity, but proper interpretation of field potentials is a long-standing challenge. Computational modeling can aid in identifying neural generators of field potentials. In the auditory brainstem of cats, spatial patterns of sound-evoked can resemble, strikingly, generated by current dipoles. Previously, we developed a biophysically-based model of a binaural brainstem nucleus, the medial superior olive (MSO), that accounts qualitatively for observed dipole-like patterns in sustained responses to monaural tones with frequencies >∼1000 Hz (Goldwyn et al., 2014). We have observed, however, that patterns in cats of both sexes appear more monopole-like for lower-frequency tones. Here, we enhance our theory to accurately reproduce dipole and non-dipole features of responses to monaural tones with frequencies ranging from 600 to 1800 Hz. By applying our model to data, we estimate time courses of paired input currents to MSO neurons. We interpret these inputs as dendrite-targeting excitation and soma-targeting inhibition (the latter contributes non-dipole-like features to responses). Aspects of inferred inputs are consistent with synaptic inputs to MSO neurons including the tendencies of inhibitory inputs to attenuate in response to high-frequency tones and to precede excitatory inputs. Importantly, our updated theory can be tested experimentally by blocking synaptic inputs. MSO neurons perform a critical role in sound localization and binaural hearing. By solving an inverse problem to uncover synaptic inputs from patterns we provide a new perspective on MSO physiology. Extracellular voltages (field potentials) are a common measure of brain activity. Ideally, one could infer from these data the activity of neurons and synapses that generate field potentials, but this "inverse problem" is not easily solved. We study brainstem field potentials in the region of the medial superior olive (MSO); a critical center in the auditory pathway. These field potentials exhibit distinctive spatial and temporal patterns in response to pure tone sounds. We use mathematical modeling in combination with physiological and anatomical knowledge of MSO neurons to plausibly explain how dendrite-targeting excitation and soma-targeting inhibition generate these field potentials. Inferring putative synaptic currents from field potentials advances our ability to study neural processing of sound in the MSO.
细胞外电压记录（即场电位）能让我们直观地了解神经活动，但对场电位进行恰当解读一直是个长期挑战。计算建模有助于确定场电位的神经发生器。在猫的听觉脑干中，声音诱发的场电位空间模式与电流偶极子产生的模式惊人地相似。此前，我们构建了一个基于生物物理学的双耳脑干核团——内侧上橄榄核（MSO）模型，该模型定性地解释了在频率大于约1000赫兹的单耳纯音持续反应中观察到的类似偶极子的场电位模式（戈德温等人，2014年）。然而，我们观察到，对于低频纯音，两性猫的场电位模式似乎更像单极子。在此，我们完善我们的理论，以准确再现频率范围为600至1800赫兹的单耳纯音反应中场电位的偶极子和非偶极子特征。通过将我们的模型应用于数据，我们估计了MSO神经元成对输入电流的时间进程。我们将这些输入解释为靶向树突的兴奋和靶向胞体的抑制（后者为场电位反应贡献非偶极子样特征）。推断出的输入方面与MSO神经元的突触输入一致，包括抑制性输入响应高频纯音而衰减以及先于兴奋性输入的趋势。重要的是，我们更新后的理论可以通过阻断突触输入进行实验验证。MSO神经元在声音定位和双耳听觉中起着关键作用。通过解决一个逆问题，从场电位模式中揭示突触输入，我们为MSO生理学提供了一个新视角。细胞外电压（场电位）是大脑活动的常用测量指标。理想情况下，人们可以从这些数据推断产生场电位的神经元和突触的活动，但这个“逆问题”并不容易解决。我们研究内侧上橄榄核（MSO）区域的脑干场电位；听觉通路中的一个关键中枢。这些场电位在对纯音声音的反应中表现出独特的空间和时间模式。我们结合MSO神经元的生理和解剖知识使用数学建模，似是而非地解释了靶向树突的兴奋和靶向胞体的抑制如何产生这些场电位。从场电位推断假定的突触电流提高了我们研究MSO中声音神经处理的能力。
