神经科学
浦肯野细胞
攀缘纤维
去抑制
小脑
原发性震颤
加巴能
去氢骆驼蓬碱
平行光纤
下橄榄核
小脑深核
心理学
抑制性突触后电位
生物
小脑皮质
精神科
作者
Steven Bellows,Joohi Jimenez-Shahed
出处
期刊:Elsevier eBooks
[Elsevier]
日期:2022-01-01
卷期号:: 285-310
被引量:2
标识
DOI:10.1016/bs.irn.2022.02.006
摘要
Although essential tremor is common, its underlying pathophysiology remains uncertain, and several hypotheses seek to explain the tremor mechanism. The GABA hypothesis states that disinhibition of deep cerebellar neurons due to reduced GABAergic input from Purkinje cells results in increased pacemaker activity, leading to rhythmic output to the thalamo-cortical circuit and resulting in tremor. However, some neuroimaging, spectroscopy, and pathology studies have not shown a clear or consistent GABA deficiency in essential tremor, and animal models have indicated that large reductions of Purkinje cell inhibition may improve tremor. Instead, tremor is increasingly attributable to dysfunction in oscillating networks, where altered (but not necessarily reduced) inhibitory signaling can result in tremor. Hypersynchrony of Purkinje cell activity may account for excessive oscillatory cerebellar output, with potential contributions along multiple sites of the olivocerebellar loop. Although older animal tremor models, such as harmaline tremor, have explored contributions from the inferior olivary body, increasing evidence has pointed to the role of aberrant climbing fiber synaptic organization in oscillatory cerebellar activity and tremor generation. New animal models such as hotfoot17j mice, which exhibit abnormal climbing fiber organization due to mutations in Grid2, have recapitulated many features of ET. Similar abnormal climbing fiber architecture and excessive cerebellar oscillations as measured by EEG have been found in humans with essential tremor. Further understanding of hypersynchrony and excessive oscillatory activity in ET phenotypes may lead to more targeted and effective treatment options.
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