Center for Hearing and Deafness, University at Buffalo , Buffalo, New York.
J Neurophysiol. 2019 Mar 1;121(3):893-907. doi: 10.1152/jn.00053.2018. Epub 2019 Jan 9.
Electrophysiological and imaging studies from humans suggest that the phantom sound of tinnitus is associated with abnormal thalamocortical neural oscillations (dysrhythmia) and enhanced gamma band activity in the auditory cortex. However, these models have seldom been tested in animal models where it is possible to simultaneously assess the neural oscillatory activity within and between the thalamus and auditory cortex. To explore this issue, we used multichannel electrodes to examine the oscillatory behavior of local field potentials recorded in the rat medial geniculate body (MBG) and primary auditory cortex (A1) before and after administering a dose of sodium salicylate (SS) that reliably induces tinnitus. In the MGB, SS reduced theta, alpha, and beta oscillations and decreased coherence (synchrony) between electrode pairs in theta, alpha, and beta bands but increased coherence in the gamma band. Within A1, SS significantly increased gamma oscillations, decreased theta power, and decreased coherence between electrode pairs in theta and alpha bands but increased coherence in the gamma band. When coherence was measured between one electrode in the MGB and another in A1, SS decreased coherence in beta, alpha, and theta bands but increased coherence in the gamma band. SS also increased cross-frequency coupling between the phase of theta oscillations in the MGB and amplitude of gamma oscillations in A1. Altogether, our results suggest that SS treatment fundamentally alters the manner in which thalamocortical circuits communicate, leading to excessive cortical gamma power and synchronization, neurophysiological changes implicated in tinnitus. Our data provide support for elements of both the thalamocortical dysrhythmia (TD) and synchronization by loss of inhibition (SLIM) models of tinnitus, demonstrating that increased cortical gamma band activity is associated with both enhanced theta-gamma coupling as well as decreases alpha power/coherence between the MGB and A1. NEW & NOTEWORTHY There are no effective drugs to alleviate the phantom sound of tinnitus because the physiological mechanisms leading to its generation are poorly understood. Neural models of tinnitus suggest that it arises from abnormal thalamocortical oscillations, but these models have not been extensively tested. This article identifies abnormal thalamocortical oscillations in a drug-induced tinnitus model. Our findings open up new avenues of research to investigate whether cellular mechanisms underlying thalamocortical oscillations are causally linked to tinnitus.
电生理和影像学研究表明，耳鸣的幻听与丘脑皮质神经振荡异常（节律紊乱）和听觉皮层中增强的伽马波段活动有关。然而，这些模型很少在动物模型中进行测试，而在动物模型中可以同时评估丘脑和听觉皮层内和之间的神经振荡活动。为了探索这个问题，我们使用多通道电极在给大鼠内侧膝状体（MBG）和初级听觉皮层（A1）记录局部场电位之前和之后检查了水杨酸钠（SS）给药后的振荡行为，SS 可靠地诱导了耳鸣。在 MGB 中，SS 降低了θ、α 和β振荡，并降低了θ、α 和β波段电极对之间的相干性（同步性），但增加了γ波段的相干性。在 A1 中，SS 显著增加了γ振荡，降低了θ功率，并降低了θ和α波段电极对之间的相干性，但增加了γ波段的相干性。当测量 MGB 中的一个电极与 A1 中的另一个电极之间的相干性时，SS 降低了β、α 和θ波段的相干性，但增加了γ波段的相干性。SS 还增加了 MGB 中θ振荡的相位和 A1 中γ振荡的幅度之间的交叉频率耦合。总的来说，我们的结果表明，SS 处理从根本上改变了丘脑皮质电路通信的方式，导致皮质γ功率和同步性过度，这是耳鸣的神经生理学变化。我们的数据为耳鸣的丘脑皮质节律紊乱（TD）和抑制丧失同步（SLIM）模型的元素提供了支持，表明皮质γ波段活动的增加与增强的θ-γ耦合以及 MGB 和 A1 之间的α功率/相干性降低有关。新与值得注意的是，由于对导致其产生的生理机制知之甚少，因此没有有效的药物可以缓解耳鸣的幻听。耳鸣的神经模型表明，它是由异常的丘脑皮质振荡引起的，但这些模型尚未得到广泛测试。本文在药物诱导的耳鸣模型中确定了异常的丘脑皮质振荡。我们的发现为研究丘脑皮质振荡的细胞机制是否与耳鸣有因果关系开辟了新的研究途径。
