Tian Guilian, Hui May, Macchia Desiree, Derdeyn Pieter, Rogers Alexandra, Hubbard Elizabeth, Liu Chengfeng, Vasquez Jose J, Taniguchi Lara, Bartas Katrina, Carroll Sean, Beier Kevin T
Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92617, USA.
Program in Mathematical, Computational, and Systems Biology, University of California, Irvine, Irvine, CA 92617, USA.
Cell Rep. 2022 May 3;39(5):110775. doi: 10.1016/j.celrep.2022.110775.
Although midbrain dopamine (DA) circuits are central to motivated behaviors, our knowledge of how experience modifies these circuits to facilitate subsequent behavioral adaptations is limited. Here we demonstrate the selective role of a ventral tegmental area DA projection to the amygdala (VTA→amygdala) for cocaine-induced anxiety but not cocaine reward or sensitization. Our rabies virus-mediated circuit mapping approach reveals a persistent elevation in spontaneous and task-related activity of inhibitory GABAergic cells from the bed nucleus of the stria terminalis (BNST) and downstream VTA→amygdala cells that can be detected even after a single cocaine exposure. Activity in BNST→midbrain cells is related to cocaine-induced anxiety but not reward or sensitization, and silencing this projection prevents development of anxiety during protracted withdrawal after cocaine administration. Finally, we observe that VTA→amygdala cells are strongly activated after a challenge exposure to cocaine and that activity in these cells is necessary and sufficient for reinstatement of cocaine place preference.
尽管中脑多巴胺（DA）回路对于动机行为至关重要，但我们对于经验如何改变这些回路以促进后续行为适应的了解仍然有限。在这里，我们证明了腹侧被盖区向杏仁核的DA投射（VTA→杏仁核）在可卡因诱导的焦虑中具有选择性作用，但对可卡因奖赏或敏化作用则不然。我们采用狂犬病病毒介导的回路映射方法发现，终纹床核（BNST）的抑制性GABA能细胞以及下游VTA→杏仁核细胞的自发活动和与任务相关的活动持续升高，即使在单次接触可卡因后也能检测到。BNST→中脑细胞的活动与可卡因诱导的焦虑有关，但与奖赏或敏化无关，并且沉默该投射可防止可卡因给药后长期戒断期间焦虑的发展。最后，我们观察到，在再次接触可卡因后，VTA→杏仁核细胞被强烈激活，并且这些细胞的活动对于恢复可卡因位置偏爱是必要且充分的。
