Activation of a Habenulo-Raphe Circuit Is Critical for the Behavioral and Neurochemical Consequences of Uncontrollable Stress in the Male Rat.
Activation of a Habenulo-Raphe Circuit Is Critical for the Behavioral and Neurochemical Consequences of Uncontrollable Stress in the Male Rat.
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DOI：
10.1523/eneuro.0229-16.2016
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发表时间：
2016-09
期刊：
影响因子：
3.4
通讯作者：
Maier SF
中科院分区：
文献类型：
--
作者：
Dolzani SD;Baratta MV;Amat J;Agster KL;Saddoris MP;Watkins LR;Maier SF
暴露于无法控制的应激[不可避免的尾休克（IS）]会产生行为变化，如果应激源是可控的[可避免的尾休克（ES）]，则不会发生这种变化，这是由更大的IS诱导的中缝背核（DRN）5-羟色胺（5-HT）激活介导的结果。有人提出，这种差异激活的发生是因为控制的存在导致内侧前额叶皮层（mPFC）对DRN的自上而下的抑制，而不是因为不可控性产生更大的兴奋性输入。尽管mPFC对DRN 5-HT激活的抑制性调节已经受到相当多的关注，但在应激期间驱动DRN 5-HT的相关兴奋性输入还没有。外侧缰核（LHb）提供了一个主要的兴奋性输入到DRN，但很少有人知道LHb在调节DRN依赖性行为的作用。在这里，IS期间LHb的光遗传学沉默阻断了雄性大鼠中IS产生的典型焦虑样行为。此外，LHb沉默阻断细胞外基底外侧杏仁核5-HT在IS期间的增加，令人惊讶的是，在第二天的行为测试期间。我们还提供了证据表明，LHb-DRN通路的激活是不敏感的行为控制的尺寸。总体而言，这些实验突出了LHb在驱动DRN激活和5-HT释放到下游回路中的关键作用，该下游回路介导IS的焦虑样行为结果，并进一步支持行为控制不调节DRN的兴奋性输入的观点。
Exposure to uncontrollable stress [inescapable tailshock (IS)] produces behavioral changes that do not occur if the stressor is controllable [escapable tailshock (ES)] an outcome that is mediated by greater IS-induced dorsal raphe nucleus (DRN) serotonin [5-hydroxytryptamine (5-HT)] activation. It has been proposed that this differential activation occurs because the presence of control leads to top–down inhibition of the DRN from medial prefrontal cortex (mPFC), not because uncontrollability produces greater excitatory input. Although mPFC inhibitory regulation over DRN 5-HT activation has received considerable attention, the relevant excitatory inputs that drive DRN 5-HT during stress have not. The lateral habenula (LHb) provides a major excitatory input to the DRN, but very little is known about the role of the LHb in regulating DRN-dependent behaviors. Here, optogenetic silencing of the LHb during IS blocked the typical anxiety-like behaviors produced by IS in male rats. Moreover, LHb silencing blocked the increase in extracellular basolateral amygdala 5-HT during IS and, surprisingly, during behavioral testing the following day. We also provide evidence that LHb–DRN pathway activation is not sensitive to the dimension of behavioral control. Overall, these experiments highlight a critical role for LHb in driving DRN activation and 5-HT release into downstream circuits that mediate anxiety-like behavioral outcomes of IS and further support the idea that behavioral control does not modulate excitatory inputs to the DRN.