导水管周围灰质中PAC1受体对冻结和逃跑行为的调节。

IF 2.4 4区 心理学 Q2 BEHAVIORAL SCIENCES
Ersin Yavas, Irina Zhuravka, Michael S. Fanselow
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引用次数: 0

摘要

中脑导水管周围灰质区(PAG)是与恐惧相关的物种特异性防御反应(SSDRs)的重要解剖学调节器。垂体腺苷酸环化酶激活多肽(PACAP)及其主要受体PAC1在恐惧相关行为和焦虑障碍中起重要作用。然而,PAG内部PACAP-PAC1系统在ssdr方面的作用却很少受到关注。为了解决这一空白,我们使用转基因PAC1flox/flox小鼠来研究条件和无条件防御反应。我们使用编码Cre重组酶的腺相关病毒(AAV)在PAC1flox/flox小鼠腹侧(vl)PAG中进行了条件PAC1基因缺失。在病毒表达之后,我们使用白噪音恐惧条件反射准备,产生无条件的活动爆发,然后是条件冻结。在第1天,小鼠接受5次白噪声足震配对,而在第2天,小鼠在没有电击的情况下接受5次白噪声,我们对白噪声的活动爆发和冻结进行了评分。行为学测试后,进行组织免疫荧光分析,分别鉴定PACAP阳性细胞和应激诱导的c-fos活性。我们发现,在vlPAG中,PAC1的缺失增加了无条件活动爆发反应,但破坏了条件冻结。行为实验后,PAC1缺失伴随着更高的c-fos活性。此外,相当一部分PACAP-EGFP阳性细胞与VGAT重叠表达,表明它们与抑制性神经元有关。研究结果表明,完整的PACAP-PAC1机制对于vlPAG的SSDRs至关重要。因此,中脑PACAP有助于调节恐惧反应的潜在分子机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

PAC1 receptor modulation of freezing and flight behavior in periaqueductal gray

PAC1 receptor modulation of freezing and flight behavior in periaqueductal gray

PAC1 receptor modulation of freezing and flight behavior in periaqueductal gray

The midbrain periaqueductal gray (PAG) region is a critical anatomical regulator of fear-related species-specific defensive reactions (SSDRs). Pituitary adenylate-cyclase-activating polypeptide (PACAP), and its main receptor PAC1, play an important role in fear-related behavior and anxiety disorders. However, the function of the PACAP-PAC1 system within the PAG with regards to SSDRs has received little attention. To address this gap, we used transgenic PAC1flox/flox mice to examine both conditional and unconditional defensive reactions. We performed conditional PAC1 gene deletion within the ventrolateral(vl)PAG of PAC1flox/flox mice using an adeno-associated virus (AAV) coding for Cre recombinase. Following viral expression, we used a white noise fear conditioning preparation that produces both an unconditional activity burst to the onset of noise that is followed by conditional freezing. On Day 1, mice received five white noise foot-shock pairings, whereas on Day 2, they were exposed to white noise five times without shock and we scored the activity burst and freezing to the white noise. Following behavioral testing, histology for immunofluorescent analysis was conducted in order to identify PACAP positive cells and stress-induced c-fos activity respectively. We found that PAC1 deletion in vlPAG increased the unconditional activity burst response but disrupted conditional freezing. PAC1 deletion was accompanied by higher c-fos activity following the behavioral experiments. Furthermore, a significant portion of PACAP-EGFP positive cells showed overlapping expression with VGAT, indicating their association with inhibitory neurons. The findings suggested that intact PACAP-PAC1 mechanisms are essential for SSDRs in vlPAG. Therefore, midbrain PACAP contributes to the underlying molecular mechanisms regulating fear responses.

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来源期刊
Genes Brain and Behavior
Genes Brain and Behavior 医学-行为科学
CiteScore
6.80
自引率
4.00%
发文量
62
审稿时长
4-8 weeks
期刊介绍: Genes, Brain and Behavior was launched in 2002 with the aim of publishing top quality research in behavioral and neural genetics in their broadest sense. The emphasis is on the analysis of the behavioral and neural phenotypes under consideration, the unifying theme being the genetic approach as a tool to increase our understanding of these phenotypes. Genes Brain and Behavior is pleased to offer the following features: 8 issues per year online submissions with first editorial decisions within 3-4 weeks and fast publication at Wiley-Blackwells High visibility through its coverage by PubMed/Medline, Current Contents and other major abstracting and indexing services Inclusion in the Wiley-Blackwell consortial license, extending readership to thousands of international libraries and institutions A large and varied editorial board comprising of international specialists.
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