Graham B P, Dutia M B
Institute for Adaptive and Neural Computation, Division of Informatics, 5 Forrest Hill, Edinburgh EH1 2QL, UK.
Exp Brain Res. 2001 Apr;137(3-4):387-96. doi: 10.1007/s002210100677.
In this study we used a cellular network model of the brainstem vestibulo-ocular reflex (VOR) pathways to investigate the role of the vestibular commissural system in "vestibular compensation", the behavioural recovery that takes place after unilateral labyrinthectomy (UL). The network was initialized on the basis of mathematical analysis and trial simulations to generate a VOR response with a physiologically realistic gain and time constant. The effects of a selective decrease in the strength of commissural inhibitory input to the ipsi-lesional medial vestibular nucleus (MVN) neurones, without changes in other parts of the network, were investigated. Thus we simulated the marked down-regulation of GABA receptor efficacy that our recent experimental results have demonstrated in these cells after UL. The main outcome of this study is the delineation, for the first time, of a specific region of parameter space within which an adaptive change in commissural inhibitory gain is appropriate and sufficient to bring about a re-balancing of bilateral vestibular nucleus activity after UL. For this to be achieved, the relative contribution of the intrinsic, pacemaker-like membrane properties of the ipsi-lesional MVN cells must be equal to or greater than the synaptic input from the primary vestibular afferents in determining the in vivo resting discharge rate of these cells. Recent experimental evidence supports the view that the intrinsic properties of the MVN cells do contribute substantially to their resting discharge in vivo. Previous modelling studies that have excluded a role for the commissural system in vestibular compensation have arrived at this conclusion, because their models operated outside this region of parameter space. A second finding of this study is that, in a network that compensates through a selective change in commissural gain, the time constant of the VOR response is significantly reduced, mimicking the loss of velocity storage after UL in vivo. By contrast, the time constant is unchanged in a network that compensates through changes involving other nonvestibular inputs. These findings indicate that adaptive changes in commissural gain, through the dynamic regulation of GABA receptor efficacy in the vestibular nucleus neurones, may play an important role in vestibular plasticity.
在本研究中，我们使用了脑干前庭眼反射（VOR）通路的细胞网络模型，来研究前庭连合系统在“前庭代偿”中的作用，前庭代偿是单侧迷路切除（UL）后发生的行为恢复。该网络基于数学分析和试验模拟进行初始化，以产生具有生理现实增益和时间常数的VOR反应。研究了选择性降低同侧损伤内侧前庭核（MVN）神经元的连合抑制性输入强度的影响，而网络其他部分无变化。因此，我们模拟了我们最近的实验结果所证明的UL后这些细胞中GABA受体效能的显著下调。本研究的主要结果是首次描绘了参数空间的一个特定区域，在该区域内，连合抑制增益的适应性变化是适当且足以在UL后实现双侧前庭核活动重新平衡的。要实现这一点，同侧损伤MVN细胞的内在起搏器样膜特性的相对贡献，在决定这些细胞的体内静息放电率时，必须等于或大于来自初级前庭传入神经的突触输入。最近的实验证据支持MVN细胞的内在特性在体内对其静息放电有很大贡献的观点。以前排除连合系统在前庭代偿中作用的建模研究得出了这一结论，因为它们的模型在这个参数空间区域之外运行。本研究的第二个发现是，在通过连合增益的选择性变化进行代偿的网络中，VOR反应的时间常数显著降低，模拟了体内UL后速度存储的丧失。相比之下，在通过涉及其他非前庭输入的变化进行代偿的网络中，时间常数不变。这些发现表明，通过前庭核神经元中GABA受体效能的动态调节，连合增益的适应性变化可能在前庭可塑性中起重要作用。
