Paraventricular thalamus mediates context-induced reinstatement (renewal) of extinguished reward seeking
Paraventricular thalamus mediates context-induced reinstatement (renewal) of extinguished reward seeking
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DOI：
10.1111/j.1460-9568.2009.06623.x
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发表时间：
2009-02-01
影响因子：
3.4
通讯作者：
McNally, Gavan P.
中科院分区：
文献类型：
--
作者：
Hamlin, Adam S.;Clemens, Kelly J.;McNally, Gavan P.
室旁丘脑（PvTh）在药物和奖励寻求的恢复中具有独特的作用。它广泛地投射到包括伏隔壳（AcbSh）、前额皮质（PFC）和基底外侧杏仁核（BLA）在内的与恢复有关的区域，并接收来自其他对恢复重要的区域（如外侧下丘脑）的传入事件。我们使用互补的神经解剖学和功能方法来研究PvTh在情境诱导的消失的奖励寻求的恢复（更新）中的作用。我们将神经元示踪剂霍乱毒素B亚基（CTb）应用于AcbSh，并检测PvTh和其他AcbSh传入事件中逆行标记的神经元、c-Fos免疫反应性（IR）和双c-Fos/CTb标记的神经元。在PvTh中，与更新相关的ctb阳性神经元中存在c-Fos IR，显示更新过程中PvTh- acbsh通路的激活。在PFC中，与更新相关的ctb阳性或阴性神经元中几乎没有c-Fos IR。在BLA中，观察到两种不同的激活模式和逆行标记。在吻侧BLA中，与更新相关的ctb阴性神经元中存在显著的c-Fos IR。在尾侧BLA中，cbb阳性神经元中存在显著的c-Fos IR，这与在消失（ABB）或训练（ABA）环境下进行测试有关。然后我们研究了PvTh在更新中的功能作用。PvTh的兴奋性毒性病变阻止了更新。这些损伤对获得寻求奖励没有影响。这些结果表明，PvTh介导环境诱导的恢复，这种更新与PvTh- acbsh通路的募集有关。
Paraventricular thalamus (PvTh) is uniquely placed to contribute to reinstatement of drug and reward seeking. It projects extensively to regions implicated in reinstatement including accumbens shell (AcbSh), prefrontal cortex (PFC) and basolateral amygdala (BLA), and receives afferents from other regions important for reinstatement such as lateral hypothalamus. We used complementary neuroanatomical and functional approaches to study the role of PvTh in context-induced reinstatement (renewal) of extinguished reward-seeking. Rats were trained to respond for a reward in context A, extinguished in context B and tested in context A or B. We applied the neuronal tracer cholera toxin B subunit (CTb) to AcbSh and examined retrograde-labelled neurons, c-Fos immunoreactivity (IR) and dual c-Fos/CTb labelled neurons in PvTh and other AcbSh afferents. In PvTh there was c-Fos IR in CTb-positive neurons associated with renewal showing activation of a PvTh-AcbSh pathway during renewal. In PFC there was little c-Fos IR in CTb-positive or negative neurons associated with renewal. In BLA, two distinct patterns of activation and retrograde labelling were observed. In rostral BLA there was significant c-Fos IR in CTb-negative neurons associated with renewal. In caudal BLA there was significant c-Fos IR in CTb-positive neurons associated with being tested in either the extinction (ABB) or training (ABA) context. We then studied the functional role of PvTh in renewal. Excitotoxic lesions of PvTh prevented renewal. These lesions had no effect on the acquisition of reward seeking. These results show that PvTh mediates context-induced reinstatement and that this renewal is associated with recruitment of a PvTh-AcbSh pathway.