nature20121220-6

来自斯坦福大学的研究人员分离出了一些神经元,证实它们专门负责决定是否值得提供能量付诸努力来完成某项任务。这一研究发现将有助于医务专业人员更好地应对抑郁症和其他脑相关疾病。

-2012年12月20日《自然》


中文翻译


【题目】控制对行为挑战反应的额前皮质-脑干神经投射

【译文】前额皮质(PFC)被认为参与了行为(包括执行作用的决定)产生的高水平控制中;其实,人类中成像和损害研究已经揭示了PFC功能紊乱会引起具有对起始行动趋向增加的冲动状态或活动减少、绝望及情绪低落等症状的缺乏动机状态。考虑到这两种表型相对的效价以及其他归因于PFC的任务的宽泛复杂性,我们力争阐释支持对挑战刺激的努力行为反应的PFC回路。本研究开发并利用一种定量方法联合单单位电生理学和光遗传学以持续性评估和控制自由运动小鼠对行为挑战的活化反应。在对中间PFC(mPFC)的记录中,我们观察到许多神经元在它们信号激发模式中不只是运动相关的,而是每时每刻都被选择性地调控,这与动物在挑战情况下行动的决定相一致。令人惊讶的是,我们进一步发现mPFC中主要神经元的直接活化并没有对这种行为产生可检测的致因性影响。我们检测了是否这种行为可能被由特异性下游布线定义的mPFC细胞亚群有原因性地介导。确实,通过影响光遗传学投射-靶向以控制具有传输布线模式的细胞,我们发现那些投射到脑干中缝背核(DRN)—与严重抑郁性障碍相关的含血清素核—的mPFC细胞的选择性活化可诱导对激活行为状态选择的一种深度、快速以及可逆的效应。这些结果可能在理解行为选择和行为动机正常和病理模式潜在神经回路时具有重要意义。

英文原稿


[Title]: A prefrontal cortex–brainstem neuronal projection that controls response to behavioural challenge

[Authors]:Melissa R. Warden,1 Aslihan Selimbeyoglu,1, 2 Julie J. Mirzabekov,1 Maisie Lo,3 Kimberly R. Thompson,1 Sung-Yon Kim,1, 2 Avishek Adhikari,1 Kay M. Tye,1, 4 Loren M. Frank5, 6 & Karl Deisseroth1, 2, 7, 8, 9

[Abstract]The prefrontal cortex (PFC) is thought to participate in high-level control of the generation of behaviours (including the decision to execute actions); indeed, imaging and lesion studies in human beings have revealed that PFC dysfunction can lead to either impulsive states with increased tendency to initiate action, or to amotivational states characterized by symptoms such as reduced activity, hopelessness and depressed mood. Considering the opposite valence of these two phenotypes as well as the broad complexity of other tasks attributed to PFC, we sought to elucidate the PFC circuitry that favours effortful behavioural responses to challenging situations. Here we develop and use a quantitative method for the continuous assessment and control of active response to a behavioural challenge, synchronized with single-unit electrophysiology and optogenetics in freely moving rats. In recording from the medial PFC (mPFC), we observed that many neurons were not simply movement-related in their spike-firing patterns but instead were selectively modulated from moment to moment, according to the animal’s decision to act in a challenging situation. Surprisingly, we next found that direct activation of principal neurons in the mPFC had no detectable causal effect on this behaviour. We tested whether this behaviour could be causally mediated by only a subclass of mPFC cells defined by specific downstream wiring. Indeed, by leveraging optogenetic projection-targeting to control cells with specific efferent wiring patterns, we found that selective activation of those mPFC cells projecting to the brainstem dorsal raphe nucleus (DRN), a serotonergic nucleus implicated in major depressive disorder, induced a profound, rapid and reversible effect on selection of the active behavioural state. These results may be of importance in understanding the neural circuitry underlying normal and pathological patterns of action selection and motivation in behaviour.

原文地址

http://www.nature.com/nature/journal/v492/n7429/full/nature11617.html

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