Molecular and Cellular Adaptations in Hippocampal Parvalbumin Neurons Mediate Behavioral Responses to Chronic Social Stress.
Molecular and Cellular Adaptations in Hippocampal Parvalbumin Neurons Mediate Behavioral Responses to Chronic Social Stress.
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DOI：
10.3389/fnmol.2022.898851
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发表时间：
2022
影响因子：
4.8
通讯作者：
Kim, Yong
中科院分区：
文献类型：
--
作者：
Bhatti, Dionnet L.;Medrihan, Lucian;Chen, Michelle X.;Jin, Junghee;McCabe, Kathryn A.;Wang, Wei;Azevedo, Estefania P.;Ledo, Jose H.;Kim, Yong
表达小白蛋白的中间神经元(PV神经元)维持对环境应激源行为反应中涉及的局部回路的抑制性控制。然而，PV神经元的分子和细胞适应在应激敏感性或恢复力中的作用尚不清楚。在这里，我们展示了慢性社会失败应激(CSDS)的行为结果是由小鼠海马PV神经元中不同的神经元活动和基因表达介导的。利用体内电生理学和化学遗传学，我们发现增加腹侧齿状回PV神经元的活性是必要的，也是行为易感性的充分条件。PV神经元选择性翻译图谱表明，线粒体氧化磷酸化是应激敏感小鼠和弹性小鼠中最显著的变化途径。在与应激敏感性和韧性相关的差异表达基因中，我们发现了AHNAK，它是L类钙通道的内源性调节因子，参与线粒体功能和基因表达的调节。值得注意的是，PV神经元中AHNAK的缺失阻碍了对CSDS的行为易感性。综上所述，这些发现表明，慢性应激的行为效应可以通过选择性地调节PV神经元的活动或调节PV神经元上的L型钙信号来控制。
Parvalbumin-expressing interneurons (PV neurons) maintain inhibitory control of local circuits implicated in behavioral responses to environmental stressors. However, the roles of molecular and cellular adaptations in PV neurons in stress susceptibility or resilience have not been clearly established. Here, we show behavioral outcomes of chronic social defeat stress (CSDS) are mediated by differential neuronal activity and gene expression in hippocampal PV neurons in mice. Using in vivo electrophysiology and chemogenetics, we find increased PV neuronal activity in the ventral dentate gyrus is required and sufficient for behavioral susceptibility to CSDS. PV neuron-selective translational profiling indicates mitochondrial oxidative phosphorylation is the most significantly altered pathway in stress-susceptible versus resilient mice. Among differentially expressed genes associated with stress-susceptibility and resilience, we find Ahnak, an endogenous regulator of L-type calcium channels which are implicated in the regulation of mitochondrial function and gene expression. Notably, Ahnak deletion in PV neurons impedes behavioral susceptibility to CSDS. Altogether, these findings indicate behavioral effects of chronic stress can be controlled by selective modulation of PV neuronal activity or a regulator of L-type calcium signaling in PV neurons.
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影响因子：
64.8
作者：
Autry, Anita E.;Adachi, Megunai;Nosyreva, Elena;Na, Elisa S.;Los, Maarten F.;Cheng, Peng-fei;Kavalali, Ege T.;Monteggia, Lisa M.
通讯作者：
Monteggia, Lisa M.
DOI：
10.1126/science.1249240
发表时间：
2014-04-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Friedman AK;Walsh JJ;Juarez B;Ku SM;Chaudhury D;Wang J;Li X;Dietz DM;Pan N;Vialou VF;Neve RL;Yue Z;Han MH
通讯作者：
Han MH
影响因子：
16.2
作者：
Fanselow, Michael S.;Dong, Hong-Wei
通讯作者：
Dong, Hong-Wei
影响因子：
7.2
作者：
Daneman, Richard;Prat, Alexandre
通讯作者：
Prat, Alexandre
影响因子：
7.6
作者：
Harris, Alexander Z.;Atsak, Piray;Gordon, Joshua A.
通讯作者：
Gordon, Joshua A.