Bagot Rosemary C, Parise Eric M, Peña Catherine J, Zhang Hong-Xing, Maze Ian, Chaudhury Dipesh, Persaud Brianna, Cachope Roger, Bolaños-Guzmán Carlos A, Cheer Joseph F, Deisseroth Karl, Han Ming-Hu, Nestler Eric J
Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, Florida 32306, USA.
Nat Commun. 2015 May 8;6:7062. doi: 10.1038/ncomms8062.
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.
伏隔核（NAc）是奖赏和动机的关键区域，该区域谷氨酸能传递增强与抑郁症的病理生理学有关；然而，这种谷氨酸水平升高的传入来源尚不清楚。伏隔核接收来自内侧前额叶皮质（mPFC）、腹侧海马体（vHIP）和基底外侧杏仁核（AMY）的谷氨酸能输入。在此，我们证明伏隔核的谷氨酸能腹侧海马体传入神经调节对慢性社会挫败应激（CSDS）的易感性。我们观察到对CSDS有抵抗力的小鼠腹侧海马体活动减少。此外，通过光遗传学诱导长时程抑制来减弱腹侧海马体-伏隔核的传递具有抗应激作用，而急性增强这种输入则易导致应激。这种效应是腹侧海马体向伏隔核的传入神经所特有的，因为对伏隔核的内侧前额叶皮质或杏仁核传入神经进行光遗传学刺激具有抗应激作用。这些数据表明，腹侧海马体向伏隔核的传入神经独特地调节对CSDS的易感性，突出了抑郁症中一种重要的、新的回路特异性机制。
