Manning Claire E, Williams Elizabeth S, Robison Alfred J
Department of Physiology, Michigan State UniversityEast Lansing, MI, USA.
Front Behav Neurosci. 2017 Apr 28;11:77. doi: 10.3389/fnbeh.2017.00077. eCollection 2017.
Over the past three decades, it has become clear that aberrant function of the network of interconnected brain regions responsible for reward processing and motivated behavior underlies a variety of mood disorders, including depression and anxiety. It is also clear that stress-induced changes in reward network activity underlying both normal and pathological behavior also cause changes in gene expression. Here, we attempt to define the reward circuitry and explore the known and potential contributions of activity-dependent changes in gene expression within this circuitry to stress-induced changes in behavior related to mood disorders, and contrast some of these effects with those induced by exposure to drugs of abuse. We focus on a series of immediate early genes regulated by stress within this circuitry and their connections, both well-explored and relatively novel, to circuit function and subsequent reward-related behaviors. We conclude that IEGs play a crucial role in stress-dependent remodeling of reward circuitry, and that they may serve as inroads to the molecular, cellular, and circuit-level mechanisms of mood disorder etiology and treatment.
在过去三十年中，已经明确负责奖励处理和动机行为的相互连接的脑区网络的异常功能是包括抑郁症和焦虑症在内的多种情绪障碍的基础。同样明确的是，应激诱导的奖励网络活动变化在正常和病理行为中均会导致基因表达的改变。在此，我们试图定义奖励回路，并探索该回路内基因表达的活性依赖性变化对与情绪障碍相关的应激诱导行为变化的已知和潜在贡献，并将其中一些效应与滥用药物所诱导的效应进行对比。我们关注该回路内受应激调节的一系列即刻早期基因及其与回路功能和随后与奖励相关行为的联系，这些联系既有深入研究的，也有相对新颖的。我们得出结论，即刻早期基因在奖励回路的应激依赖性重塑中起关键作用，并且它们可能为情绪障碍病因和治疗的分子、细胞和回路水平机制提供切入点。
