Johnston Alex R, Seckl Jonathan R, Dutia Mayank B
Department of Biomedical Sciences (Physiology), Edinburgh University Medical School, Hugh Robson Building, George Square, Edinburgh EH8 9XD, Scotland, UK.
J Physiol. 2002 Dec 15;545(3):903-11. doi: 10.1113/jphysiol.2002.024281.
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 de-afferentation, 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 1 expression in cerebellum.
我们研究了小脑绒球在介导前庭代偿过程中脑干内侧前庭核（MVN）神经元内在特性发生的适应性变化中的作用。患侧绒球切除而非对侧绒球切除，可阻止去传入的MVN神经元在单侧迷路切除（UL）后4小时内正常发生的内在兴奋性代偿性增加（CIE）。然而，绒球切除并未阻止UL后这些神经元中也会出现的GABA受体效能下调，这表明MVN神经元对去传入的这些反应是离散的、平行的过程。向绒球内微量注射代谢型谷氨酸受体（mGluR）拮抗剂艾达（AIDA）和蛋白激酶C抑制剂双吲哚马来酰亚胺I（BIS-I）也可消除CIE。丝氨酸 - 苏氨酸激酶抑制剂H-7在去传入时微量注射没有效果，但如果在2小时后微量注射则可消除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。它们表明前庭代偿期间MVN神经元内在兴奋性的增加依赖于小脑，并且需要小脑皮质中的mGluR激活和蛋白磷酸化。此外，向患侧绒球内微量注射糖皮质激素受体（GR）拮抗剂RU38486也可消除MVN神经元中的CIE。因此，糖皮质激素促进前庭代偿的一个重要部位在小脑皮质内。这些观察结果赋予了小脑内高水平GR和11-β-羟基类固醇脱氢酶1型表达的功能意义。
