Role of the flocculus in mediating vestibular nucleus neuron plasticity during vestibular compensation in the rat
Role of the flocculus in mediating vestibular nucleus neuron plasticity during vestibular compensation in the rat
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DOI：
10.1113/jphysiol.2002.024281
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发表时间：
2002-12-15
影响因子：
5.5
通讯作者：
Dutia, MB
中科院分区：
文献类型：
--
作者：
Johnston, AR;Seckl, JR;Dutia, MB
我们研究了小脑絮球在介导前庭代偿期间脑干内侧前庭核（MVN）神经元固有特性发生的适应性变化中的作用。同侧病变（而非对侧病变）的絮状切除术阻止了内在兴奋性（CIE）的代偿性增加，这种兴奋性通常在单侧迷路切除术（UL）后 4 小时内发生在传入神经阻滞的 MVN 神经元中。然而，絮状切除术并不能阻止 UL 后这些神经元中 GABA 受体功效的下调，这表明 MVN 神经元对传入神经阻滞的这些反应是离散的、并行的过程。 CIE 也通过絮内显微注射代谢型谷氨酸受体 (mGluR) 拮抗剂 AIDA 和蛋白激酶 C 抑制剂双吲哚马来酰亚胺 I (BIS-I) 来消除。丝氨酸苏氨酸激酶抑制剂H-7在传入神经阻滞时显微注射没有作用，但如果2小时后显微注射则消除了CIE。这些细胞效应与最近报道的 BIS-I 和 H-7 对 UL 后行为恢复的延迟作用一致。他们证明，前庭代偿期间 MVN 神经元内在兴奋性的增加是小脑依赖性的，并且需要小脑皮质中 mGluR 的激活和蛋白质磷酸化。此外，将糖皮质激素受体 (GR) 拮抗剂 RU38486 显微注射到同位病变绒球中也消除了 MVN 神经元中的 CIE。因此，糖皮质激素促进前庭代偿的重要部位是小脑皮质内。这些观察结果将功能意义归因于小脑中高水平的 GR 和 11-β-HSD I 型表达。
We investigated the role of the cerebellar flocculus in mediating the adaptive changes that occur in the intrinsic properties of brainstem medial vestibular nucleus (MVN) neurons during vestibular compensation. Ipsi-lesional, but not contra-lesional, flocculectomy prevented the compensatory increase in intrinsic excitability (CIE) that normally occurs in the de-afferented MVN neurons within 4 h after unilateral labyrinthectomy (UL). Flocculectomy did not, however, prevent the down-regulation of efficacy of GABA receptors that also occurs in these neurons after UL, indicating that these responses of the MVN neurons to deafferentation are discrete, parallel processes. CIE was also abolished by intra-floccular microinjection of the metabotropic glutamate receptor (mGluR) antagonist AIDA, and the protein kinase C inhibitor bisindolymaleimide I (BIS-I). The serene-threonine kinase inhibitor H-7 had no effect when microinjected at the time of deafferentation, but abolished CIE if microinjected 2 h later. These cellular effects are in line with the recently reported retardatory effects of BIS-I and H-7 on behavioural recovery after UL. They demonstrate that the increase in intrinsic excitability in MVN neurons during vestibular compensation is cerebellum dependent, and requires mGluR activation and protein phosphorylation in cerebellar cortex. Furthermore, microinjection of the glucocorticoid receptor (GR) antagonist RU38486 into the ipsi-lesional flocculus also abolished CIE in MVN neurons. Thus an important site for glucocorticoids in facilitating vestibular compensation is within the cerebellar cortex. These observations ascribe functional significance to the high levels of GR and 11-beta-HSD Type I expression in cerebellum.