非人类灵长类动物光遗传学对精神病学疗效的实用再评价

Oxford open neuroscience Pub Date : 2022-04-29 eCollection Date: 2022-01-01 DOI:10.1093/oons/kvac006
Eliza Bliss-Moreau, Vincent D Costa, Mark G Baxter
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引用次数: 0

摘要

转化神经科学致力于在实验室中产生最终能够改善人类生活的发现。光遗传学因其在啮齿类动物大脑中操纵细胞和电路的前景而受到相当大的关注。在最近的一份报告中,Tremblay等人[28]介绍了一个开放资源,详细介绍了非人灵长类动物(NHP)大脑的光遗传学研究,并对该技术的可翻译性提出了强有力的主张。我们认为,他们的定量(例如91%的成功率)和理论主张是值得怀疑的,因为数据是在与啮齿动物相关但与NHP大脑无关的水平上分析的,在少数大脑区域的少数研究中,注射集中在少数猴子身上,并且他们对成功的定义与人类神经精神疾病没有明确的相关性。对数据进行重新分析,对成功的定义进行了修改,其中包括行为和生物学效应,结果显示,62.5%的成功率在仅考虑强结果时较低(53.1%)。这让人对光遗传学技术在NHP大脑中的当前疗效产生了质疑,并表明我们离利用它们为正如Tremblay报告所说的那样。
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A pragmatic reevaluation of the efficacy of nonhuman primate optogenetics for psychiatry.

Translational neuroscience is committed to generating discoveries in the laboratory that ultimately can improve human lives. Optogenetics has received considerable attention because of its demonstrated promise in rodent brains to manipulate cells and circuits. In a recent report, Tremblay et al. [28] introduce an open resource detailing optogenetic studies of the nonhuman primate (NHP) brain and make robust claims about the translatability of the technology. We propose that their quantitative (e.g. a 91% success rate) and theoretical claims are questionable because the data were analyzed at a level relevant to the rodent but not NHP brain. Injections were clustered within a few monkeys in a few studies in a few brain regions, and their definitions of success were not clearly relevant to human neuropsychiatric disease. A reanalysis of the data with a modified definition of success that included a behavioral and biological effect revealed a 62.5% success rate that was lower when considering only strong outcomes (53.1%). This calls into question the current efficacy of optogenetic techniques in the NHP brain and suggests that we are a long way from being able to leverage them in 'the service of patients with neurological or psychiatric conditions' as the Tremblay report claims.

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