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Converging structural and functional evidence for a rat salience network
Biological Psychiatry ( IF 9.6 ) Pub Date : 2020-12-01 , DOI: 10.1016/j.biopsych.2020.06.023
Pei-Jung Tsai , Robin J. Keeley , Stephanie A. Carmack , Janaina C.M. Vendruscolo , Hanbing Lu , Hong Gu , Leandro F. Vendruscolo , George F. Koob , Ching-Po Lin , Elliot A. Stein , Yihong Yang

BACKGROUND The salience network (SN) is dysregulated in many neuropsychiatric disorders, including substance use disorder. Though the SN was initially described in humans, identification of a rodent SN would provide the ability to mechanistically interrogate this network in preclinical models of neuropsychiatric disorders. METHODS We used modularity analysis on resting-state functional magnetic resonance imaging data of rats (n = 32) to parcellate rat insula into functional subdivisions and to identify a potential rat SN based on functional connectivity patterns from the insular subdivisions. We then used mouse tract tracing data from the Allen Brain Atlas to confirm the network's underlying structural connectivity. We next compared functional connectivity profiles of the SN across rats, marmosets (n = 10), and humans (n = 30). Finally, we assessed the rat SN's response to conditioned cues in rats (n = 21) with a history of heroin self-administration. RESULTS We identified a putative rat SN, which consists of primarily the ventral anterior insula and anterior cingulate cortex, based on functional connectivity patterns from the ventral anterior insular division. Functional connectivity architecture of the rat SN is supported by the mouse neuronal tracer data. Moreover, the anatomical profile of the identified rat SN is similar to that of nonhuman primates and humans. Finally, we demonstrated that the rat SN responds to conditioned cues and increases functional connectivity to the default mode network during conditioned heroin withdrawal. CONCLUSIONS The neurobiological identification of a rat SN, together with a demonstration of its functional relevance, provides a novel platform with which to interrogate its functional significance in normative and neuropsychiatric disease models.

中文翻译:

融合大鼠显着网络的结构和功能证据

背景显着网络(SN)在许多神经精神障碍中失调,包括物质使用障碍。虽然最初在人类中描述了 SN,但识别啮齿动物 SN 将提供在神经精神疾病的临床前模型中机械地询问该网络的能力。方法我们对大鼠(n = 32)的静息状态功能磁共振成像数据进行模块化分析,将大鼠岛叶分成功能细分,并根据岛叶细分的功能连接模式识别潜在的大鼠 SN。然后,我们使用来自 Allen Brain Atlas 的鼠标束追踪数据来确认网络的潜在结构连通性。我们接下来比较了大鼠、狨猴 (n = 10) 和人类 (n = 30) 的 SN 的功能连接特征。最后,我们评估了大鼠 SN 对有海洛因自我给药史的大鼠(n = 21)的条件线索的反应。结果我们根据腹侧前岛叶分裂的功能连接模式确定了一个推定的大鼠 SN,其主要由腹侧前岛叶和前扣带回皮层组成。小鼠神经元示踪数据支持大鼠 SN 的功能连接架构。此外,鉴定出的大鼠 SN 的解剖学特征与非人类灵长类动物和人类的解剖学特征相似。最后,我们证明了大鼠 SN 对条件线索作出反应,并在条件海洛因戒断期间增加了与默认模式网络的功能连接。结论 大鼠 SN 的神经生物学鉴定,以及其功能相关性的证明,
更新日期:2020-12-01
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