Eppendorf finalist. Striatal interneurons: causes of or cures for movement disorders?
Eppendorf finalist. Striatal interneurons: causes of or cures for movement disorders?
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艾彭多夫决赛入围者。
DOI：
10.1126/science.1229852
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Gittis,Aryn
中科院分区：
文献类型：
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作者：
Gittis,Aryn
Imagine one day you notice a tremor and can’t walk easily anymore. Your doctor tells you that you have Parkinson’s disease and gives you levodopa, a 60-year-old treatment that temporarily relieves your symptoms. But over time, the medication makes you impulsive, and after a few years, your symptoms return. The doctor tells you that you have developed resistance to your medicine and that nothing else is likely to work—your condition continues to degenerate. Sadly, this is the reality for millions of Americans suffering from Parkinson’s disease. This need not be the case. Despite half a century in which huge strides have been made in our understanding of the causes of Parkinson’s disease, our treatments are still largely based on the oversimplified idea that augmenting dopamine is all that matters. For the last two decades, we have known that Parkinson’s disease, as well as a number of other movement disorders, result from an imbalance in the activity of two opposing neural pathways in a brain region called the striatum (1–3). Overactivity of the “direct pathway” promotes disorders of excessive movement, such as Huntington’s disease, dystonia, and Tourette syndrome; overactivity of the “indirect pathway” promotes disorders of insufficient movement, such as Parkinson’s disease. Why have we not transformed this model into effective therapies for movement disorders? Most therapeutic interventions fail because they do not target the direct or indirect pathways with sufficient precision in human patients. Better therapies will require a deeper understanding of the organizing principles of striatal circuits. Can we find neurons that selectively tune output of the direct and indirect pathways? I believe the answer is yes, if we target fast-spiking interneurons (FSIs).FSIs belong to a family of neurons called inhibitory interneurons, which specialize in controlling firing rate and timing of activity across ensembles of neurons. Because neurons in the striatum of patients with movement disorders show abnormalities in both rate and timing, I hypothesized that dysfunction of FSIs would be a common theme across a broad array of human diseases.
