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BNST transient activity associates with approach behavior in a stressful environment and is modulated by the parabrachial nucleus
Neurobiology of Stress ( IF 4.3 ) Pub Date : 2020-08-01 , DOI: 10.1016/j.ynstr.2020.100247
A A Jaramillo 1, 2, 3, 4 , K M Williford 1, 3, 4 , C Marshall 1, 2, 3, 4 , D G Winder 1, 2, 3, 4, 5, 6, 7 , S W Centanni 1, 2, 3, 4
Affiliation  

Studies demonstrate a role for the bed nucleus of the stria terminalis (BNST) in modulating affective behavior and stress-reward integration. To explore the dynamic nature of in vivo BNST activity associated with anxiety-like behavior in a stress-inducing context, we utilized fiber photometry and detected BNST calcium transients in mice during the novelty-suppressed feeding task (NSFT). Phasic BNST activity emerged time-locked to novel object or food pellet approach during NSFT. The parabrachial nucleus (PBN) has a large input to the BNST and is thought to function as a danger signal, in arousal responses and in feeding behavior. To explore a potential role for the PBN as a contributor to BNST activity in NSFT, we investigated whether chemogenetic regulation of PBN activity altered the dynamic BNST response synchronized to NSFT approach behavior. We found that activation of the hM3D(Gq) DREADD in the PBN enhanced the observed transient signal in the BNST synchronized to the consummatory food approach, and was associated at the behavioral level with increased latency to consume food. Because the PBN has multiple efferent pathways, we next used a transsynaptic anterograde AAV-based strategy to express hM3D(Gq) specifically in PBN-innervated BNST (BNSTPBN) neurons in male and female mice. Activation of hM3D(Gq) in these BNSTPBN neurons increased latency to consume food in female, but not male mice. To further explore the population of BNST neurons contributing to phasic BNST activity associated with NSFT, we turned to PKCδ neurons in BNST. BNST(PKCδ) neurons are implicated in stress and food-related behavior, and we previously found that the expression of this kinase is regulated in the BNST by stress in a sex-dependent manner. Here, we demonstrate close apposition of CGRP, a marker of PBN terminals, adjacent to BNST(PKCδ) cells. Finally, we find that PKCδ-expressing BNST cells exhibit a large transient signal synchronized to the consummatory food approach similar to that seen with bulk BNST activity measures. Taken together these data demonstrate phasic BNST activity at a global and cell-specific level that is driven in part by PBN activity at the time of NSFT consummatory approach behavior.



中文翻译:

BNST 瞬态活动与压力环境中的接近行为相关,并由臂旁核调节

研究证明了终纹床核 (BNST) 在调节情感行为和压力-奖励整合中的作用。探索体内的动态特性BNST 活动与应激诱导环境中的焦虑样行为相关,我们利用纤维光度法并在新奇抑制喂养任务 (NSFT) 期间检测到小鼠体内的 BNST 钙瞬变。在 NSFT 期间,阶段性 BNST 活动与新物体或食物颗粒方法出现时间锁定。臂旁核 (PBN) 对 BNST 有很大的输入,被认为在唤醒反应和进食行为中起危险信号的作用。为了探索 PBN 作为 NSFT 中 BNST 活动贡献者的潜在作用,我们研究了 PBN 活动的化学遗传学调控是否改变了与 NSFT 接近行为同步的动态 BNST 响应。我们发现激活 hM3D(G q) PBN 中的 DREADD 增强了 BNST 中观察到的瞬态信号,与完善的食物方法同步,并且在行为水平上与食用食物的延迟增加有关。因为 PBN 有多个传出通路,我们接下来使用基于跨突触顺行 AAV 的策略在雄性和雌性小鼠的 PBN 神经支配的 BNST (BNST PBN ) 神经元中特异性表达 hM3D(G q )。在这些 BNST PBN中激活 hM3D(G q )神经元增加了雌性小鼠而不是雄性小鼠进食食物的潜伏期。为了进一步探索有助于与 NSFT 相关的阶段性 BNST 活动的 BNST 神经元群,我们转向 BNST 中的 PKCδ 神经元。BNST(PKCδ)神经元与压力和食物相关行为有关,我们之前发现这种激酶的表达在 BNST 中受到压力以性别依赖性方式调节。在这里,我们展示了与 BNST(PKCδ) 细胞相邻的 PBN 末端标记物 CGRP 的紧密并置。最后,我们发现表达 PKCδ 的 BNST 细胞表现出与大量 BNST 活性测量所见的类似的完美食物方法同步的大瞬态信号。

更新日期:2020-08-01
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