Stress-induced plasticity of a CRH/GABA projection disrupts reward behaviors in mice.
Stress-induced plasticity of a CRH/GABA projection disrupts reward behaviors in mice.
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DOI：
10.1038/s41467-023-36780-x
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发表时间：
2023-02-25
影响因子：
16.6
通讯作者：
Baram, Tallie Z. Z.
中科院分区：
文献类型：
--
作者：
Birnie, Matthew T. T.;Short, Annabel K. K.;de Carvalho, Gregory B. B.;Taniguchi, Lara;Gunn, Benjamin G. G.;Pham, Aidan L. L.;Itoga, Christy A. A.;Xu, Xiangmin;Chen, Lulu Y. Y.;Mahler, Stephen V. V.;Chen, Yuncai;Baram, Tallie Z. Z.
奖励回路的运作中断是主要情绪障碍的根源，包括抑郁症，这些障碍通常在早期生活压力/逆境（ELA）后出现。然而，ELA 如何持久影响奖励回路功能仍不清楚。我们描述了连接基底外侧杏仁核 (BLA) 和伏隔核 (NAc) 的压力敏感投射，该投射共同表达 GABA 和应激反应性神经肽促肾上腺皮质激素释放激素 (CRH)。我们确定了这种投射在执行由 ELA 引起的奖励行为中断中的关键作用：对对照雄性小鼠的投射进行化学遗传学和光遗传学刺激，抑制了多种奖励行为，重现了 ELA 造成的缺陷，并证明了该通路对正常奖励行为的贡献。在成年 ELA 小鼠中，抑制（但不刺激）投射可以恢复典型的奖赏行为，但对对照组几乎没有影响，表明 ELA 诱导了该奖赏回路组件的适应不良可塑性。因此，我们发现了一种具有独特分子特征的压力敏感、奖赏抑制的 BLA → NAc 投射，这可能为致残性精神疾病提供干预目标。奖赏回路功能障碍是关键情绪障碍的一种机制，通常在早期生活压力（ELA）后出现。在这里，作者发现了从杏仁核到伏核的投射，这是 ELA 诱导的小鼠奖赏缺陷的基础。
Disrupted operations of the reward circuit underlie major emotional disorders, including depression, which commonly arise following early life stress / adversity (ELA). However, how ELA enduringly impacts reward circuit functions remains unclear. We characterize a stress-sensitive projection connecting basolateral amygdala (BLA) and nucleus accumbens (NAc) that co-expresses GABA and the stress-reactive neuropeptide corticotropin-releasing hormone (CRH). We identify a crucial role for this projection in executing disrupted reward behaviors provoked by ELA: chemogenetic and optogenetic stimulation of the projection in control male mice suppresses several reward behaviors, recapitulating deficits resulting from ELA and demonstrating the pathway’s contributions to normal reward behaviors. In adult ELA mice, inhibiting–but not stimulating–the projection, restores typical reward behaviors yet has little effect in controls, indicating ELA-induced maladaptive plasticity of this reward-circuit component. Thus, we discover a stress-sensitive, reward inhibiting BLA → NAc projection with unique molecular features, which may provide intervention targets for disabling mental illnesses. Reward circuit dysfunction is a mechanism for key emotional disorders that commonly arise after early life stresses (ELA). Here, the authors discover a projection from amygdala to nucleus accumbens that underlies ELA-induced reward deficits in mice.
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影响因子：
26.1
作者：
Baldwin JR;Caspi A;Meehan AJ;Ambler A;Arseneault L;Fisher HL;Harrington H;Matthews T;Odgers CL;Poulton R;Ramrakha S;Moffitt TE;Danese A
通讯作者：
Danese A
影响因子：
16.6
作者：
de Guglielmo, Giordano;Kallupi, Marsida;George, Olivier
通讯作者：
George, Olivier
影响因子：
--
作者：
Green, Jennifer Greif;McLaughlin, Katie A.;Berglund, Patricia A.;Gruber, Michael J.;Sampson, Nancy A.;Zaslavsky, Alan M.;Kessler, Ronald C.
通讯作者：
Kessler, Ronald C.
影响因子：
15.9
作者：
Luby JL;Baram TZ;Rogers CE;Barch DM
通讯作者：
Barch DM
影响因子：
4.8
作者：
Chen, Yuncai;Molet, Jenny;Baram, Tallie Z.
通讯作者：
Baram, Tallie Z.