Sex-Dependent Modulation of Anxiety and Fear by 5-HT1A Receptors in the Bed Nucleus of the Stria Terminalis.,ACS Chemical Neuroscience

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Sex-Dependent Modulation of Anxiety and Fear by 5-HT1A Receptors in the Bed Nucleus of the Stria Terminalis.
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2019-06-17 , DOI: 10.1021/acschemneuro.8b00594
Catherine A Marcinkiewcz _{1,

2} , Gabrielle Bierlein-De La Rosa ₁ , Cayce E Dorrier ₂ , Mackenzie McKnight ₁ , Jeffrey F DiBerto ₃ , Dipanwati Pati ₂ , Carol A Gianessi ₂ , Olivia J Hon _{2,

3} , Greg Tipton ₂ , Zoe A McElligott _{2,

3} , Eric Delpire ₄ , Thomas L Kash _{2,

3,

5}

Affiliation

Serotonin (5-hydroxytryptamine; 5-HT) coordinates behavioral responses to stress through a variety of presynaptic and postsynaptic receptors distributed across functionally diverse neuronal networks in the central nervous system. Efferent 5-HT projections from the dorsal raphe nucleus (DRN) to the bed nucleus of the stria terminalis (BNST) are generally thought to enhance anxiety and aversive learning by activating 5-HT2C receptor (5-HT2CR) signaling in the BNST, although an opposing role for postsynaptic 5-HT1A receptors has recently been suggested. In the present study, we sought to delineate a role for postsynaptic 5-HT1A receptors in the BNST in aversive behaviors using a conditional knockdown of the 5-HT1A receptor. Both males and females were tested to dissect out sex-specific effects. We found that male mice have significantly reduced fear memory recall relative to female mice and inactivation of 5-HT1A receptor in the BNST increases contextual fear conditioning in male mice so that they resemble the females. This coincided with an increase in neuronal excitability in males, suggesting that 5-HT1A receptor deletion may enhance contextual fear recall by disinhibiting fear memory circuits in the BNST. Interestingly, 5-HT1A receptor knockdown did not significantly alter anxiety-like behavior in male or female mice, which is in agreement with previous findings that anxiety and fear are modulated by dissociable circuits in the BNST. Overall, these results suggest that BNST 5-HT1A receptors do not significantly alter behavior under basal conditions, but can act as a molecular brake that buffer against excessive activation of aversive circuits in more threatening contexts.

中文翻译：

5-HT1A受体在纹状体床核中的性别依赖性焦虑和恐惧调节。

血清素（5-羟色胺； 5-HT）通过分布在中枢神经系统中功能多样的神经元网络中的各种突触前和突触后受体，协调对应激的行为反应。一般认为，从背缝核（DRN）到末梢纹床床核（BNST）的出射5-HT投射可通过激活BNST中的5-HT2C受体（5-HT2CR）信号传导来增强焦虑和厌恶性学习。最近有人提出突触后5-HT1A受体的相反作用。在本研究中，我们试图描述使用条件性5-HT1A受体在BNST中突触后5-HT1A受体在厌恶行为中的作用。男性和女性均经过测试以分析特定性别的影响。我们发现，雄性小鼠相对于雌性小鼠而言，恐惧记忆的记忆力明显降低，BNST中5-HT1A受体的失活增加了雄性小鼠的情境恐惧条件，因此它们与雌性小鼠相似。这与男性神经元兴奋性增加相吻合，表明5-HT1A受体缺失可通过抑制BNST中的恐惧记忆回路来增强情景恐惧记忆。有趣的是，5-HT1A受体的敲低并没有显着改变雄性或雌性小鼠的焦虑样行为，这与以前的发现一致，即焦虑和恐惧是由BNST中的可分离回路调节的。总体而言，这些结果表明BNST 5-HT1A受体在基础条件下不会显着改变行为，

更新日期：2019-05-29

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