Activity of a vmPFC-DRN Pathway Corresponds With Resistance to Acute Social Defeat Stress.
Activity of a vmPFC-DRN Pathway Corresponds With Resistance to Acute Social Defeat Stress.
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DOI：
10.3389/fncir.2020.00050
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发表时间：
2020
影响因子：
3.5
通讯作者：
Cooper MA
中科院分区：
文献类型：
--
作者：
Grizzell JA;Clarity TT;Graham NB;Dulka BN;Cooper MA
腹内侧前额叶皮层 (vmPFC) 通过自上而下抑制关键的压力敏感边缘和后脑结构（包括中缝背核 (DRN)），在压力恢复中发挥着关键作用。在依赖于经验的压力抵抗模型中，与从属或控制的同伴相比，处于社会主导地位的叙利亚仓鼠在严重的社会失败后表现出较少的焦虑迹象。此外，在压力期间，主导者比下属更能激活 vmPFC 神经元，并且在药物抑制 vmPFC 后变得容易受到压力影响。支配者还表现出比下属更少的压力激活 DRN 神经元，这表明支配者会经历 vmPFC 神经元的激活，从而在社交失败压力期间抑制 DRN。为了测试社会支配地位是否会改变 vmPFC-DRN 通路的应激诱导活性，我们将逆行示踪剂霍乱毒素 B (CTB) 注射到优势仓鼠、从属仓鼠和对照仓鼠的 DRN 中，并使用双标记免疫组织化学方法来鉴定与 CTB 共同标记的 vmPFC 神经元以及立即早期基因 cFos 的失败诱导表达。结果表明，与其他动物相比，优势仓鼠在 vmPFC 的下边缘和前边缘亚区域的 V/VI 层中显示出更多的 cFos+ 和双标记细胞。此外，vmPFC-DRN 激活与失败期间的主动行为策略直接对应，这表明了压力恢复能力。总之，结果表明，在急性应激期间招募 vmPFC-DRN 通路与占主导地位的仓鼠对社交失败影响的抵抗力相对应。总体而言，这些发现表明单突触 vmPFC-DRN 通路可以以依赖于经验的方式参与，这对旨在减轻与压力相关的精神病理学的行为干预具有影响。
The ventromedial prefrontal cortex (vmPFC) plays a critical role in stress resilience through top-down inhibition of key stress-sensitive limbic and hindbrain structures, including the dorsal raphe nucleus (DRN). In a model of experience-dependent stress resistance, socially dominant Syrian hamsters display fewer signs of anxiety following acute social defeat when compared to subordinate or control counterparts. Further, dominants activate vmPFC neurons to a greater degree during stress than do subordinates and become stress-vulnerable following pharmacological inhibition of the vmPFC. Dominants also display fewer stress-activated DRN neurons than subordinates do, suggesting that dominance experience gates activation of vmPFC neurons that inhibit the DRN during social defeat stress. To test whether social dominance alters stress-induced activity of a vmPFC-DRN pathway, we injected a retrograde tracer, cholera toxin B (CTB), into the DRN of dominant, subordinate, and control hamsters and used a dual-label immunohistochemical approach to identify vmPFC neurons co-labeled with CTB and the defeat-induced expression of an immediate early gene, cFos. Results indicate that dominant hamsters display more cFos+ and dual-labeled cells in layers V/VI of infralimbic and prelimbic subregions of the vmPFC compared to other animals. Furthermore, vmPFC-DRN activation corresponded directly with proactive behavioral strategies during defeat, which is indicative of stress resilience. Together, results suggest that recruiting the vmPFC-DRN pathway during acute stress corresponds with resistance to the effects of social defeat in dominant hamsters. Overall, these findings indicate that a monosynaptic vmPFC-DRN pathway can be engaged in an experience-dependent manner, which has implications for behavioral interventions aimed at alleviating stress-related psychopathologies.
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影响因子：
3.3
作者：
Morrison, K. E.;Curry, D. W.;Cooper, M. A.
通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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影响因子：
3.7
作者：
Cooper, Matthew A.;McIntyre, Kathleen E.;Huhman, Kim L.
通讯作者：
Huhman, Kim L.
影响因子：
3.3
作者：
Dulka BN;Bress KS;Grizzell JA;Cooper MA
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