Angiotensin type 1a receptors on corticotropin-releasing factor neurons contribute to the expression of conditioned fear.
Angiotensin type 1a receptors on corticotropin-releasing factor neurons contribute to the expression of conditioned fear.
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DOI：
10.1111/gbb.12235
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发表时间：
2015-09
期刊：
影响因子：
--
通讯作者：
Marvar PJ
中科院分区：
文献类型：
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作者：
Hurt RC;Garrett JC;Keifer OP Jr;Linares A;Couling L;Speth RC;Ressler KJ;Marvar PJ
尽管通常与心血管调节相关，但在小鼠模型和人类中，血管紧张素II受体1型（AT 1aR）阻断也分别与增强的恐惧消退和降低的创伤后应激障碍（PTSD）症状严重程度相关。调节这些效应的机制尚不清楚，但可能涉及促肾上腺皮质激素释放因子（CRF）表达细胞的活动改变，已知这些细胞参与恐惧调节。为了检验CRF能神经元中的AT 1aR信号传导参与条件性恐惧表达的假设，我们产生并表征了条件性敲除小鼠品系，其CRF释放细胞中的AT 1aR基因缺失（CRF-AT 1aR（−/−））。这些小鼠表现出正常的基线心率、血压、焦虑和运动，并且在获得听觉恐惧条件反射期间冻结在正常水平。然而，CRF-AT 1aR（−/−）小鼠在条件性恐惧表达测试中表现出比野生型小鼠更少的冻结-这种效应可能是由恐惧记忆巩固减少引起的。这些结果表明，中央AT 1 R活性CRF表达细胞中起着一定的作用，在条件性恐惧的表达，并确定CRFergic细胞作为一个人口AT 1 R拮抗剂可能会采取行动，以调节恐惧灭绝。
Although generally associated with cardiovascular regulation, angiotensin II receptor type 1 (AT1aR) blockade in mouse models and humans has also been associated with enhanced fear extinction and decreased post-traumatic stress disorder (PTSD) symptom severity, respectively. The mechanisms mediating these effects remain unknown, but may involve alterations in the activities of corticotropin-releasing factor (CRF)-expressing cells, which are known to be involved in fear regulation. To test the hypothesis that AT1aR signaling in CRFergic neurons is involved in conditioned fear expression, we generated and characterized a conditional knockout mouse strain with a deletion of the AT1aR gene from its CRF-releasing cells (CRF-AT1aR(−/−)). These mice exhibit normal baseline heart rate, blood pressure, anxiety, and locomotion, and freeze at normal levels during acquisition of auditory fear conditioning. However, CRF-AT1aR(−/−) mice exhibit less freezing than wild type mice during tests of conditioned fear expression—an effect that may be caused by a decrease in the consolidation of fear memory. These results suggest that central AT1R activity in CRF-expressing cells plays a role in the expression of conditioned fear, and identify CRFergic cells as a population on which AT1R antagonists may act to modulate fear extinction.