Department of Neuroscience, City University of Hong Kong, Tat Chee Avenue, Hong Kong Special Administrative Region.
Neural Netw. 2023 May;162:541-556. doi: 10.1016/j.neunet.2023.01.045. Epub 2023 Feb 2.
Computational neural network modelling is an emerging approach for optimization of drug treatment of neurological disorders and fine-tuning of rehabilitation strategies. In the current study, we constructed a cerebello-thalamo-cortical computational neural network model to simulate a mouse model of cerebellar ataxia (pcd mice) by manipulating cerebellar bursts through reduction of GABAergic inhibitory input. Cerebellar output neurons were projected to the thalamus and bidirectionally connected with the cortical network. Our results showed that reduction of inhibitory input in the cerebellum orchestrated the cortical local field potential (LFP) dynamics to generate specific motor outputs of oscillations of the theta, alpha, and beta bands in the computational model as well as in mouse motor cortical neurons. The therapeutic potential of deep brain stimulation (DBS) was tested in the computational model by increasing the sensory input to restore cortical output. Ataxia mice showed normalization of the motor cortex LFP after cerebellum DBS. We provide a novel approach to computational modelling to investigate the effect of DBS by mimicking cerebellar ataxia involving degeneration of Purkinje cells. Simulated neural activity coincides with findings from neural recordings of ataxia mice. Our computational model could thus represent cerebellar pathologies and provide insight into how to improve disease symptoms by restoring neuronal electrophysiological properties using DBS.
计算神经网络建模是一种新兴的方法,可用于优化神经疾病的药物治疗和康复策略的微调。在本研究中,我们构建了一个小脑-丘脑-皮层计算神经网络模型,通过减少 GABA 能抑制性输入来模拟小脑共济失调(pcd 小鼠)的小鼠模型。小脑输出神经元投射到丘脑,并与皮层网络双向连接。我们的结果表明,小脑抑制性输入的减少协调了皮层局部场电位(LFP)的动力学,以在计算模型中产生特定的运动输出,包括theta、alpha 和 beta 波段的振荡,以及在小鼠运动皮层神经元中。通过增加感觉输入来恢复皮层输出,在计算模型中测试了深部脑刺激(DBS)的治疗潜力。小脑 DBS 后,共济失调小鼠的运动皮层 LFP 恢复正常。我们提供了一种新的计算模型方法来研究 DBS 的效果,通过模拟涉及浦肯野细胞退化的小脑共济失调来进行。模拟的神经活动与共济失调小鼠的神经记录结果一致。因此,我们的计算模型可以代表小脑病变,并深入了解如何通过 DBS 恢复神经元电生理特性来改善疾病症状。