Kitahara T, Takeda N, Saika T, Kubo T, Kiyama H
Department of Otolaryngology, Osaka University Medical School, Japan.
Brain Res. 1995 Nov 27;700(1-2):182-90. doi: 10.1016/0006-8993(95)00950-u.
Unilateral labyrinthectomy (UL) causes ocular and postural asymmetries, which disappear over time in the processes of equilibrium recovery known as vestibular compensation. It has been reported that N-methyl-D-aspartate (NMDA) receptors are involved in vestibular compensation. In the present study, in order to elucidate the NMDA receptor-mediated neural circuit responsible for the development of vestibular compensation, we used Fos expression as a marker of neural activation and examined the effects of MK801, a specific antagonist of NMDA receptors, on UL-induced Fos expression in the rat brainstem. After UL, Fos-like immunoreactive (-LIR) neurons were observed in the ipsilateral medial vestibular nucleus (ipsi-MVe), the contralateral prepositus hypoglossal nucleus (contra-PrH) and the contralateral inferior olive beta subnucleus (contra-IOb). Fos-LIR neurons gradually disappeared in the processes of vestibular compensation. It is suggested that the activation of the ipsi-MVe, the contra-PrH and the contra-IOb neurons after UL are the initial event of vestibular compensation. Intraperitoneal injection of MK801 in the processes of vestibular compensation caused reappearance of UL-induced behavioral deficits. During the decompensation induced by MK801, Fos-LIR neurons appeared in the contra-MVe, the ipsi-PrH and the bilateral-IOB. It is suggested that the contra-MVe, the ipsi-PrH and the bilateral-IOb neurons are inhibited by glutamatergic synapses driving inhibitory neurons via NMDA receptors in the processes of vestibular compensation and that disinhibition of these nuclei induced by MK801 causes decompensation. However, MK801 caused neither Fos expression nor behavioral decompensation after vestibular compensation is accomplished. All these findings that the NMDA receptor-mediated inhibitory modulation in the central vestibular system plays an important role for the initial processes of the development of vestibular compensation.
单侧迷路切除术（UL）会导致眼部和姿势不对称，这些不对称在被称为前庭代偿的平衡恢复过程中会随着时间消失。据报道，N-甲基-D-天冬氨酸（NMDA）受体参与前庭代偿。在本研究中，为了阐明负责前庭代偿发展的NMDA受体介导的神经回路，我们使用Fos表达作为神经激活的标志物，并研究了NMDA受体的特异性拮抗剂MK801对大鼠脑干中UL诱导的Fos表达的影响。UL后，在同侧内侧前庭核（ipsi-MVe）、对侧舌下前置核（contra-PrH）和对侧下橄榄核β亚核（contra-IOb）中观察到Fos样免疫反应性（-LIR）神经元。Fos-LIR神经元在前庭代偿过程中逐渐消失。提示UL后ipsi-MVe、contra-PrH和contra-IOb神经元的激活是前庭代偿的初始事件。在前庭代偿过程中腹腔注射MK801导致UL诱导的行为缺陷再次出现。在MK801诱导的失代偿过程中，Fos-LIR神经元出现在contra-MVe、ipsi-PrH和双侧IOB中。提示在前庭代偿过程中，contra-MVe、ipsi-PrH和双侧IOb神经元受到通过NMDA受体驱动抑制性神经元的谷氨酸能突触的抑制，而MK801诱导的这些核团的去抑制导致失代偿。然而，在前庭代偿完成后，MK801既未引起Fos表达也未引起行为失代偿。所有这些发现表明，中枢前庭系统中NMDA受体介导的抑制性调节在前庭代偿发展的初始过程中起重要作用。
