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A projection from the paraventricular nucleus of the thalamus to the shell of the nucleus accumbens contributes to footshock stress-induced social avoidance
Neurobiology of Stress ( IF 5 ) Pub Date : 2020-10-31 , DOI: 10.1016/j.ynstr.2020.100266
Xinwen Dong , Sa Li , Gilbert J. Kirouac

The paraventricular nucleus of the thalamus (PVT) is an area of the dorsal midline thalamus that contributes to footshock induced anxiety. The PVT sends a dense projection to the shell of the nucleus accumbens (NAcSh) and the present study explored if this projection is involved in the behavioral changes produced by a single exposure of rats to inescapable footshocks. The inhibitory Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) hM4Di was transduced in PVT neurons that project to the NAcSh. Rats were exposed to an episode of moderately intense footshock (1.5 mA × 2 s × 5) and assigned to either high-responder (HR) or low-responder groups (LR) according to their level of fear generalization 24 h later. The effect of chemogenetic inhibition of the PVT-NAcSh projection on anxiety- and fear-like behaviors was assessed at approximately 2 weeks post-footshock. HR showed a higher level of social avoidance compared to non-shocked animals and LR. The elevated level of social avoidance was attenuated in the HR treated with the hM4Di agonist clozapine (0.01 mg/kg, i.p.) or clozapine N-oxide (CNO) administrations in the NAcSh while avoidance of open spaces and contextual fear expression were not affected. Analysis of protein product of the early to immediate gene cfos indicated that these effects were mediated by dynorphin neurons in the NAcSh. This study provides evidence for a role of a projection from the PVT to the NAcSh in stress-induced social avoidance independent of anxiety to non-social stimuli and contextual fear mechanisms.



中文翻译:

从丘脑的室旁核到伏隔核壳的投影有助于足底压力诱发的社会回避

丘脑的脑室旁核(PVT)是背侧中线丘脑的一个区域,该区域有助于足部休克引起的焦虑。PVT向伏隔核(NAcSh)的外壳发送了一个密集的投影,本研究探索了这种投影是否与大鼠单次暴露于不可避免的足底所产生的行为变化有关。被设计药物(DREADDs)独家激活的抑制性设计受体hM4Di在投射至NAcSh的PVT神经元中进行了转导。将大鼠暴露于中等强度的足部电击(1.5 mA×2 s×5)发作,并根据其在24小时后的恐惧泛化程度分为高反应者(HR)组或低反应者组(LR)。在休克后大约2周,评估了化学上抑制PVT-NAcSh投射对焦虑和恐惧样行为的影响。与非震惊动物和LR相比,HR显示出更高的社交回避感。在NAcSh中用hM4Di激动剂氯氮平(0.01 mg / kg,ip)或氯氮平N-氧化物(CNO)给药治疗的HR减轻了社交回避的升高水平,同时避免了开放空间和情境恐惧表达。早期到即刻基因的蛋白质产物分析 )或NAcSh中的氯氮平N-氧化物(CNO)给药,而避免开放空间和情境恐惧表达则不受影响。早期到即刻基因的蛋白质产物分析 )或NAcSh中的氯氮平N-氧化物(CNO)给药,而避免开放空间和情境恐惧表达则不受影响。早期到即刻基因的蛋白质产物分析cfos指出,这些作用是由NAcSh中的强啡肽神经元介导的。这项研究提供了从PVT到NAcSh的预测在压力诱发的社会回避中的作用的证据,而与社交,非社会刺激和情境恐惧机制的焦虑无关。

更新日期:2020-11-12
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