Circuit-based frameworks of depressive behaviors: The role of reward circuitry and beyond.
Circuit-based frameworks of depressive behaviors: The role of reward circuitry and beyond.
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DOI：
10.1016/j.pbb.2017.12.010
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发表时间：
2018-11
期刊：
影响因子：
--
通讯作者：
Lim BK
中科院分区：
文献类型：
--
作者：
Knowland D;Lim BK
重度抑郁症（MDD）是一种常见但严重的神经精神疾病，包括一系列不同的症状，如无法感受快乐，缺乏动力，食欲变化和认知困难。考虑到MDD患者之间的症状变异性和个体症状的不同严重程度，不同脑区的适应不良变化可能介导MDD的离散症状。使用病毒遗传学方法的研究的出现和最近的激增允许对动机行为的网络进行特定回路的解剖。特别是，腹侧被盖区（VTA）、丘脑核（NAc）和腹侧苍白球（VP）等区域被认为通常会促进奖励，内侧前额叶皮层（mPFC）提供自上而下的奖励寻求控制。相反，外侧缰（LHb）被认为是大脑的厌恶中心，因为它已被证明编码负价。MDD的行为症状可能是由于奖赏回路的中断、厌恶中枢的过度活跃或两者的结合而引起的。因此，获得对大脑内特定回路的访问，以及在单独的抑郁症相关症状的背景下，单独的动机相关区域如何在彼此之间传输和编码信息，可以为MDD的神经特异性治疗提供关键知识。在这里，我们回顾了已发表的文献，强调电路和细胞类型的特定解剖抑郁症的动物模型中的抑郁样行为，特别关注慢性社会失败压力模型的抑郁症。
Major depressive disorder (MDD) is a common but serious neuropsychiatric affliction that comprises a diverse set of symptoms such as the inability to feel pleasure, lack of motivation, changes in appetite, and cognitive difficulties. Given the patient to patient symptomatic variability in MDD and differing severities of individual symptoms, it is likely that maladaptive changes in distinct brain areas may mediate discrete symptoms in MDD. The advent and recent surge of studies using viral-genetic approaches have allowed for circuit-specific dissection of networks underlying motivational behavior. In particular, areas such as the ventral tegmental area (VTA), nucleus accumbens (NAc), and ventral pallidum (VP) are thought to generally promote reward, with the medial prefrontal cortex (mPFC) providing top-down control of reward seeking. On the contrary, the lateral habenula (LHb) is considered to be the aversive center of the brain as it has been shown to encode negative valence. The behavioral symptoms of MDD may arise from a disruption in the reward circuitry, hyperactivity of aversive centers, or a combination of the two. Thus, gaining access to specific circuits within the brain and how separate motivational-relevant regions transmit and encode information between each other in the context of separate depression-related symptoms can provide critical knowledge towards symptom-specific treatment of MDD. Here, we review published literature emphasizing circuit- and cell type-specific dissection of depressive-like behaviors in animal models of depression with a particular focus on the chronic social defeat stress model of MDD.
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