Grüsser-Cornehls U, Luy M, Bäurle J
Department of Physiology, Freie Universität Berlin, Germany.
Brain Res. 1995 Dec 12;703(1-2):51-62. doi: 10.1016/0006-8993(95)01064-5.
Neurological disorders of genetic origin that lead to distinct disarrangements of the cerebellar wiring and cause a specific motor behaviour are likely to differentially influence the response properties and activity of postsynaptic cerebellar target neurons in the deep cerebellar (DCN) and vestibular nuclei (VN). Comparative electrophysiological and morphological analyses of these neurons in different mutants may increase our understanding of the physiological consequences of cell damage to the cerebellum and help to elucidate the relationships between histopathology and severeness of motor impairment. The Leaner mutation removes GABAergic inhibitory input to the VN predominantly originating from Purkinje cells (PC) located in the anterior lobe of the cerebellum and causes extremely severe motor disability when compared to other cerebellar mutants. In the present study the electrophysiological properties of naturally stimulated (sinusoidal head and body rotation) neurons in the VN of Leaner mutants and their corresponding wild-types (C57BL/6J) were investigated. Neuronal activity of VN single units in Leaner mutants is significantly increased over that of wild-types (frequency range 0.2-0.6 Hz) and more pronounced for type I neurons than for type II. Phase relationships and spontaneous activity are similar at these frequencies in both groups. To elucidate the degree of GABAergic input loss of VN-neurons, quantitative morphometric and numerical analyses of GABA-immunopositive synaptic boutons in the lateral VN of Leaner mutants were performed in addition and revealed significantly smaller terminals and a massive decrease (80%) in Leaner mutant terminal numbers compared to controls. In the context of the findings recently obtained in Weaver and Purkinje cell degeneration (PCD) mutants, the results in Leaner suggest that the loss of inhibition due to the PC degeneration in the anterior vermis leads to a differential enhancement of type I and type II target neuron activity in the VN. The overall activity in Leaner is intermediate between PCD (no increase in activity) and Weaver (strong increase of type I but no increase of type II). GABA-immunocytochemistry supports the idea that in Leaner the lost GABAergic PC-innervation of the lateral VN has not been replaced by surviving PCs, which is in contrast to Weaver where sprouting of GABAergic terminals in this nucleus was observed. Substitution of lost cerebellar inhibition by non-cerebellar sources, as suggested in the case of PCD-mutants, is uncertain in Leaner due to the increased activity of type I target neurons. These conditions may contribute, among others, to the severe motor disturbances in Leaner.
源于遗传的神经系统疾病会导致小脑神经回路明显紊乱，并引发特定的运动行为，这可能会对小脑深部核团（DCN）和前庭核（VN）中突触后小脑靶神经元的反应特性和活动产生不同影响。对不同突变体中这些神经元进行比较电生理和形态学分析，可能会增进我们对小脑细胞损伤生理后果的理解，并有助于阐明组织病理学与运动障碍严重程度之间的关系。“瘦型”突变主要消除了源自小脑前叶浦肯野细胞（PC）对前庭核的GABA能抑制性输入，与其他小脑突变体相比，会导致极其严重的运动残疾。在本研究中，对“瘦型”突变体及其相应野生型（C57BL/6J）前庭核中自然刺激（正弦头部和身体旋转）神经元的电生理特性进行了研究。“瘦型”突变体前庭核单个神经元的活动比野生型显著增加（频率范围0.2 - 0.6 Hz），I型神经元比II型更明显。两组在这些频率下的相位关系和自发活动相似。为了阐明前庭核神经元GABA能输入丧失的程度，还对“瘦型”突变体外侧前庭核中GABA免疫阳性突触小体进行了定量形态学和数值分析，结果显示与对照组相比，其终末明显更小，且“瘦型”突变体终末数量大幅减少（80%）。结合最近在“韦弗”和浦肯野细胞变性（PCD）突变体中获得的研究结果，“瘦型”突变体的结果表明，小脑蚓部浦肯野细胞变性导致的抑制丧失会使前庭核中I型和II型靶神经元活动出现不同程度的增强。“瘦型”突变体的整体活动介于PCD（活动无增加）和“韦弗”（I型活动强烈增加但II型无增加）之间。GABA免疫细胞化学支持这样一种观点，即在“瘦型”突变体中，外侧前庭核丧失的GABA能浦肯野细胞神经支配未被存活的浦肯野细胞所取代，这与“韦弗”突变体不同，在“韦弗”突变体中观察到该核团有GABA能终末的出芽。如PCD突变体那样，由非小脑来源替代丧失的小脑抑制作用在“瘦型”突变体中并不确定，因为I型靶神经元的活动增加。这些情况可能是导致“瘦型”突变体出现严重运动障碍的部分原因。
