Bath Kevin G, Russo Scott J, Pleil Kristen E, Wohleb Eric S, Duman Ronald S, Radley Jason J
Department of Cognitive Linguistic and Psychological Sciences, Brown University, Providence, RI 02912, United States.
Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.
Neurobiol Stress. 2017 May 6;7:137-151. doi: 10.1016/j.ynstr.2017.05.001. eCollection 2017 Dec.
The current review is meant to synthesize research presented as part of a symposium at the 2016 Neurobiology of Stress workshop in Irvine California. The focus of the symposium was "Stress and the Synapse: New Concepts and Methods" and featured the work of several junior investigators. The presentations focused on the impact of various forms of stress (altered maternal care, binge alcohol drinking, chronic social defeat, and chronic unpredictable stress) on synaptic function, neurodevelopment, and behavioral outcomes. One of the goals of the symposium was to highlight the mechanisms accounting for how the nervous system responds to stress and their impact on outcome measures with converging effects on the development of pathological behavior. Dr. Kevin Bath's presentation focused on the impact of disruptions in early maternal care and its impact on the timing of hippocampus maturation in mice, finding that this form of stress drove accelerated synaptic and behavioral maturation, and contributed to the later emergence of risk for cognitive and emotional disturbance. Dr. Scott Russo highlighted the impact of chronic social defeat stress in adolescent mice on the development and plasticity of reward circuity, with a focus on glutamatergic development in the nucleus accumbens and mesolimbic dopamine system, and the implications of these changes for disruptions in social and hedonic response, key processes disturbed in depressive pathology. Dr. Kristen Pleil described synaptic changes in the bed nuclei of the stria terminalis that underlie the behavioral consequences of allostatic load produced by repeated cycles of alcohol binge drinking and withdrawal. Dr. Eric Wohleb and Dr. Ron Duman provided new data associating decreased mammalian target of rapamycin (mTOR) signaling and neurobiological changes in the synapses in response to chronic unpredictable stress, and highlighted the potential for the novel antidepressant ketamine to rescue synaptic and behavioral effects. In aggregate, these presentations showcased how divergent perspectives provide new insights into the ways in which stress impacts circuit development and function, with implications for understanding emergence of affective pathology.
本综述旨在综合作为2016年在加利福尼亚州欧文市举办的应激神经生物学研讨会上一个专题讨论会一部分所展示的研究。该专题讨论会的重点是“应激与突触：新概念与方法”，展示了几位初级研究人员的工作。报告聚焦于各种形式的应激（母体护理改变、暴饮酒精、慢性社会挫败和慢性不可预测应激）对突触功能、神经发育和行为结果的影响。该专题讨论会的目标之一是强调解释神经系统如何对应激作出反应的机制及其对结果测量指标的影响，这些影响对病理行为的发展具有汇聚效应。凯文·巴斯博士的报告聚焦于早期母体护理中断的影响及其对小鼠海马体成熟时间的影响，发现这种应激形式促使突触和行为加速成熟，并导致后期出现认知和情绪障碍风险。斯科特·鲁索博士强调了慢性社会挫败应激对青春期小鼠奖赏回路发育和可塑性的影响，重点关注伏隔核和中脑边缘多巴胺系统中的谷氨酸能发育，以及这些变化对社会和享乐反应中断的影响，而这些反应是抑郁病理中受到干扰的关键过程。克里斯汀·普莱尔博士描述了终纹床核中的突触变化，这些变化是由反复的酒精暴饮和戒断循环产生的应激负荷行为后果的基础。埃里克·沃勒布博士和罗恩·杜曼博士提供了新数据，将雷帕霉素哺乳动物靶点（mTOR）信号传导减少与慢性不可预测应激反应中突触的神经生物学变化联系起来，并强调了新型抗抑郁药氯胺酮挽救突触和行为效应的潜力。总体而言，这些报告展示了不同的观点如何为应激影响神经回路发育和功能的方式提供新的见解，这对于理解情感病理学的出现具有重要意义。
