Dysfunction in amygdala-prefrontal plasticity and extinction-resistant avoidance: A model for anxiety disorder vulnerability.
Dysfunction in amygdala-prefrontal plasticity and extinction-resistant avoidance: A model for anxiety disorder vulnerability.
复制标题
杏仁核前额叶可塑性和抗灭绝性回避的功能障碍：焦虑症脆弱性的模型。
DOI：
10.1016/j.expneurol.2015.11.002
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发表时间：
2016-01
影响因子：
5.3
通讯作者：
Beck KD
中科院分区：
文献类型：
--
作者：
Fragale JE;Khariv V;Gregor DM;Smith IM;Jiao X;Elkabes S;Servatius RJ;Pang KC;Beck KD
表现出焦虑症的个体被认为具有先天的脆弱性，使他们容易患上这种疾病。焦虑症也与杏仁核和前额叶皮层（PFC）的相互连接的大脑区域的异常有关。然而，焦虑脆弱性和杏仁核-PFC功能障碍之间的联系目前尚不清楚。因此，本研究试图确定是否先天功能障碍的杏仁核PFC投射的易感性发展焦虑样行为的基础上，使用焦虑脆弱的啮齿动物模型。使用近交系Wistar京都（WKY）大鼠来模拟脆弱性，因为该品系天然表达抵抗性回避;一种模拟焦虑症中存在的回避症状的行为。在WKY和Sprague道利（SD）大鼠杏仁核基底外侧核（BLA）向PFC边缘前皮质亚区的投射中，评价了突触可塑性。虽然WKY大鼠表现出正常的成对脉冲可塑性，但它们不像SD大鼠那样保持长时程增强（LTP）。因此，受损的可塑性内的BLA-PL皮质的投影可能有助于灭绝抵抗回避WKY，在SD大鼠的PL皮质病变损害灭绝回避类似WKY大鼠。用d-环丝氨酸治疗WKY大鼠以逆转受损的LTP是不成功的。WKY大鼠LTP的缺乏与PL皮质中含有NR 2A亚基的NMDA受体的显著减少有关。因此，杏仁核-PFC可塑性的功能障碍是焦虑易感大鼠的先天特征，并可能通过破坏杏仁核和前额叶皮质之间的沟通来促进抗焦虑回避。
Individuals exhibiting an anxiety disorder are believed to possess an innate vulnerability that makes them susceptible to the disorder. Anxiety disorders are also associated with abnormalities in the interconnected brain regions of the amygdala and prefrontal cortex (PFC). However, the link between anxiety vulnerability and amygdala-PFC dysfunction is currently unclear. Accordingly, the present study sought to determine if innate dysfunction within the amygdala to PFC projection underlies the susceptibility to develop anxiety-like behavior, using an anxiety vulnerable rodent model. The inbred Wistar Kyoto (WKY) rat was used to model vulnerability, as this strain naturally expresses extinction-resistant avoidance; a behavior that models the symptom of avoidance present in anxiety disorders. Synaptic plasticity was assessed within the projection from the basolateral nucleus of the amygdala (BLA) to the prelimbic cortical subdivision of the PFC in WKY and Sprague Dawley (SD) rats. While WKY rats exhibited normal paired-pulse plasticity, they did not maintain long-term potentiation (LTP) as SD rats. Thus, impaired plasticity within the BLA-PL cortex projection may contribute to extinction resistant avoidance of WKY, as lesions of the PL cortex in SD rats impaired extinction of avoidance similar to WKY rats. Treatment with d-cycloserine to reverse the impaired LTP in WKY rats was unsuccessful. The lack of LTP in WKY rats was associated with a significant reduction of NMDA receptors containing NR2A subunits in the PL cortex. Thus, dysfunction in amygdala-PFC plasticity is innate in anxiety vulnerable rats and may promote extinction-resistant avoidance by disrupting communication between the amygdala and prefrontal cortex.