ChAT::Cre transgenic rats show sex-dependent altered fear behaviors, ultrasonic vocalizations and cholinergic marker expression.
ChAT::Cre transgenic rats show sex-dependent altered fear behaviors, ultrasonic vocalizations and cholinergic marker expression.
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CHAT :: CRE转基因大鼠表现出与性别有关的改变恐惧行为，超声波声和胆碱能标记的表达。
DOI：
10.1111/gbb.12837
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发表时间：
2023-02
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影响因子：
--
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胆碱能系统是巴甫洛夫恐惧学习和消退的关键调节器。因此，我们已经开始调查胆碱能系统的参与个体差异线索恐惧灭绝使用转基因ChAT：：Cre大鼠模型。目前的研究扩展了行为表型的转基因ChAT：：Cre大鼠线通过检查冻结行为和超声波发声（USVs）在巴甫洛夫线索恐惧学习和灭绝的范例。在雄性和雌性转基因ChAT：：Cre+大鼠及其野生型（Cre‐）同窝仔之间比较了冷冻、22 kHz USV和50 kHz USV在恐惧学习、情境和线索条件下的恐惧回忆、线索恐惧消退和对新音调的概括过程中的作用。在情境和线索恐惧回忆期间，ChAT：：Cre+大鼠比Cre同窝出生的大鼠略多冻结，并且在情境和线索条件冻结、22 kHz USV和50 kHz USV中显示出显著的性别差异。女性表现出更多的冻结比男性在恐惧回忆试验，但较少的22 kHz的痛苦呼叫在恐惧学习和回忆。女性也产生了更多的50 kHz的USV在暴露于测试室之前，音调（或休克）介绍与男性相比，但这种影响是钝化ChAT：：Cre+女性。证实了先前的研究，ChAT：：Cre+转基因大鼠在基底前脑、纹状体、基底外侧杏仁核和海马中过表达囊泡乙酰胆碱转运蛋白免疫标记，但乙酰胆碱酯酶水平和ChAT+神经元数量与Cre-大鼠相似。这项研究表明，ChAT：：Cre+和野生型大鼠之间的行为差异是性别依赖的，并提出了不同的神经回路和过程调节性差异恐惧反应的理论。本研究探讨冻结和超声波发声（USVs）在恐惧条件反射和恐惧灭绝的范例，加上囊泡乙酰胆碱转运蛋白（VAChT）的表达，在男性和女性的转基因ChAT：：Cre大鼠与野生型同窝仔相比。结果表明，与VAChT过表达相关的ChAT：：Cre+和野生型大鼠的恐惧反应具有性别依赖性。在恐惧回忆过程中，ChAT：：Cre+大鼠的冻结程度略高于其Cre-野生型同窝仔，并且在情境和线索条件冻结、22 kHz USV和50 kHz USV中显示出显著的性别差异。女性表现出较少的22 kHz的遇险呼叫比男性在恐惧的学习和回忆，但产生更多的50 kHz的USVs在暴露于测试室相比，男性。
The cholinergic system is a critical regulator of Pavlovian fear learning and extinction. As such, we have begun investigating the cholinergic system's involvement in individual differences in cued fear extinction using a transgenic ChAT::Cre rat model. The current study extends behavioral phenotyping of a transgenic ChAT::Cre rat line by examining both freezing behavior and ultrasonic vocalizations (USVs) during a Pavlovian cued fear learning and extinction paradigm. Freezing, 22 kHz USVs, and 50 kHz USVs were compared between male and female transgenic ChAT::Cre+ rats and their wildtype (Cre‐) littermates during fear learning, contextual and cue‐conditioned fear recall, cued fear extinction, and generalization to a novel tone. During contextual and cued fear recall ChAT::Cre+ rats froze slightly more than their Cre‐ littermates, and displayed significant sex differences in contextual and cue‐conditioned freezing, 22 kHz USVs, and 50 kHz USVs. Females showed more freezing than males in fear recall trials, but fewer 22 kHz distress calls during fear learning and recall. Females also produced more 50 kHz USVs during exposure to the testing chambers prior to tone (or shock) presentation compared with males, but this effect was blunted in ChAT::Cre+ females. Corroborating previous studies, ChAT::Cre+ transgenic rats overexpressed vesicular acetylcholine transporter immunolabeling in basal forebrain, striatum, basolateral amygdala, and hippocampus, but had similar levels of acetylcholinesterase and numbers of ChAT+ neurons as Cre‐ rats. This study suggests that variance in behavior between ChAT::Cre+ and wildtype rats is sex dependent and advances theories that distinct neural circuits and processes regulate sexually divergent fear responses. This study examined freezing and ultrasonic vocalizations (USVs) during a fear conditioning and fear extinction paradigm, plus expression of vesicular acetylcholine transporter (VAChT), in both male and female transgenic ChAT::Cre rats compared with their wildtype littermates. Results showed that fear responses in ChAT::Cre+ and wildtype rats related to the VAChT overexpression are sex‐dependent. During fear recall ChAT::Cre+ rats froze slightly more than their Cre‐ wildtype littermates, and displayed significant sex differences in contextual and cue‐conditioned freezing, 22 kHz USVs, and 50 kHz USVs. Females showed fewer 22 kHz distress calls than males during fear learning and recall, but produced more 50 kHz USVs during exposure to the testing chambers compared with males.
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3.1
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