Corticotrophin releasing factor-induced synaptic plasticity in the amygdala translates stress into emotional disorders
Corticotrophin releasing factor-induced synaptic plasticity in the amygdala translates stress into emotional disorders
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DOI：
10.1523/jneurosci.5740-03.2004
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发表时间：
2004-04-07
影响因子：
5.3
通讯作者：
Shekhar, A
中科院分区：
文献类型：
--
作者：
Rainnie, DG;Bergeron, R;Shekhar, A
杏仁核参与了食欲和厌恶情绪的联想过程，其功能受到应激激素的调节。神经肽促肾上腺皮质激素释放因子（CRF）在应激过程中释放，并与许多应激相关的行为，自主神经和内分泌反应有关。在本研究中，nonanxiety-inducing剂量的一个有效的CRF 1型和2型受体激动剂，尿皮质素（UCN），局部注入到基底外侧杏仁核（BLA）的大鼠。每天注射5次UCN后，动物在行为测试中出现焦虑样反应。静脉注射抗焦虑剂乳酸钠可引起血压、呼吸频率和心率的显著升高。此外，在没有任何额外的UCN治疗的情况下，这些行为和自主反应持续>30天。全细胞膜片钳记录从BLA神经元的这些高反应性的动物显示了显着减少自发和刺激诱发的IPSPs，导致超兴奋性的BLA网络。这种Ucn诱导的可塑性似乎依赖于NMDA受体和随后的钙-钙调蛋白依赖性蛋白激酶II（CaMKII）的激活，因为它被阻断预处理与NMDA受体拮抗剂和共同管理的CaMKII抑制剂。我们的研究结果首次显示了一种应激肽诱导的行为综合征，这种综合征与神经可塑性的细胞机制有关，这是一种新的机制，可以解释应激在几种慢性精神和医学疾病中的病因作用。
The amygdala is involved in the associative processes for both appetitive and aversive emotions, and its function is modulated by stress hormones. The neuropeptide corticotrophin releasing factor (CRF) is released during stress and has been linked to many stress-related behavioral, autonomic, and endocrine responses. In the present study, nonanxiety-inducing doses of a potent CRF type 1 and 2 receptor agonist, urocortin (Ucn), was infused locally into the basolateral amygdala (BLA) of rats. After 5 daily injections of Ucn, the animals developed anxiety-like responses in behavioral tests. Intravenous administration of the anxiogenic agent sodium lactate elicited robust increases in blood pressure, respiratory rate, and heart rate. Furthermore, in the absence of any additional Ucn treatment, these behavioral and autonomic responses persisted for >30 d. Whole-cell patch-clamp recordings from BLA neurons of these hyper-reactive animals revealed a pronounced reduction in both spontaneous and stimulation-evoked IPSPs, leading to a hyperexcitability of the BLA network. This Ucn-induced plasticity appears to be dependent on NMDA receptor and subsequent calcium-calmodulin-dependent protein kinase II (CaMKII) activation, because it is blocked by pretreatment with NMDA receptor antagonists and by coadministration of CaMKII inhibitors. Our results show for the first time a stress peptide-induced behavioral syndrome that can be correlated with cellular mechanisms of neural plasticity, a novel mechanism that may explain the etiological role of stress in several chronic psychiatric and medical disorders.