Ventral hippocampal afferents to the nucleus accumbens regulate susceptibility to depression.
Ventral hippocampal afferents to the nucleus accumbens regulate susceptibility to depression.
复制标题
腹侧海马传入伏隔核调节抑郁的易感性。
DOI：
10.1038/ncomms8062
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发表时间：
2015-05-08
影响因子：
16.6
通讯作者：
Nestler, Eric J.
中科院分区：
文献类型：
--
作者：
Bagot, Rosemary C.;Parise, Eric M.;Pena, Catherine J.;Zhang, Hong-Xing;Maze, Ian;Chaudhury, Dipesh;Persaud, Brianna;Cachope, Roger;Bolanos-Guzman, Carlos A.;Cheer, Joseph;Deisseroth, Karl;Han, Ming-Hu;Nestler, Eric J.
在对奖励和动机至关重要的丘脑核（NAc）中，谷氨酸能传递增强，这与抑郁症的病理生理学有关;然而，这种谷氨酸张力增加的传入来源尚不清楚。NAc接收来自内侧前额叶皮层（mPFC）、腹侧海马（vHIP）和基底外侧杏仁核（AMY）的海马能输入。在这里，我们表明，NAc的神经元能vHIP传入调节慢性社会失败压力（CSDS）的易感性。我们观察到对CSDS有弹性的小鼠中vHIP的活性降低。此外，通过长期抑郁的光遗传学诱导的vHIP-NAc传递的衰减是亲弹性的，而这种输入的急性增强是亲易感的。这种效应对NAc的vHIP传入是特异性的，因为对NAc的mPFC或AMY传入的光遗传学刺激是亲弹性的。这些数据表明，vHIP传入NAc独特的调节易感性CSDS，突出了一个重要的，新的电路特定的机制，抑郁症。 在抑郁症的病理生理学中，中脑核（NAc）中增强的多巴胺能传递有牵连，但其潜在的来源尚不清楚。在这里，作者证明了腹侧海马-NAc神经元投射在调节抑郁样行为中的独特作用。
Enhanced glutamatergic transmission in the nucleus accumbens (NAc), a region critical for reward and motivation, has been implicated in the pathophysiology of depression; however, the afferent source of this increased glutamate tone is not known. The NAc receives glutamatergic inputs from the medial prefrontal cortex (mPFC), ventral hippocampus (vHIP) and basolateral amygdala (AMY). Here, we demonstrate that glutamatergic vHIP afferents to NAc regulate susceptibility to chronic social defeat stress (CSDS). We observe reduced activity in vHIP in mice resilient to CSDS. Furthermore, attenuation of vHIP-NAc transmission by optogenetic induction of long-term depression is pro-resilient, whereas acute enhancement of this input is pro-susceptible. This effect is specific to vHIP afferents to the NAc, as optogenetic stimulation of either mPFC or AMY afferents to the NAc is pro-resilient. These data indicate that vHIP afferents to NAc uniquely regulate susceptibility to CSDS, highlighting an important, novel circuit-specific mechanism in depression. Enhanced glutamatergic transmission in the nucleus accumbens (NAc) has been implicated in the pathophysiology of depression, yet the underlying source is not known. Here, the authors demonstrate a unique role for ventral hippocampal-NAc glutamatergic projections in regulating depression-like behaviour.
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作者：
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