Serotonergic neurons signal reward and punishment on multiple timescales.
Serotonergic neurons signal reward and punishment on multiple timescales.
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DOI：
10.7554/elife.06346
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发表时间：
2015-02-25
期刊：
影响因子：
7.7
通讯作者：
Uchida N
中科院分区：
文献类型：
--
作者：
Cohen JY;Amoroso MW;Uchida N
血清素在大脑中的功能尚不清楚。测试有关血清素功能的众多假设的一个挑战是观察从事行为任务的动物中已识别的血清素能神经元的活动。我们记录了小鼠中缝背神经元的活动，同时小鼠经历了一项奖励和惩罚在不同试验组中有所不同的任务。我们用光敏蛋白通道视紫红质 2 来“标记”血清素能神经元，并根据它们对光的反应来识别它们。我们发现了血清素能神经元活动的三个主要特征：（1）大部分血清素能神经元在奖励与惩罚块期间在几分钟内调节其强直放电率； （2）大多数人因惩罚而出现阶段性兴奋； (3) 一个子集因奖励预测线索而出现阶段性兴奋。相比之下，多巴胺能神经元在试验中没有表现出放电率变化。这些结果表明，血清素能神经元在多个时间尺度上发出有关奖励和惩罚的信息。 DOI：http://dx.doi.org/10.7554/eLife.06346.001 奖励和惩罚都可以鼓励动物改变其当前行为并影响其长期情绪，特别是重复给予时。大脑中因奖励和惩罚而增加活动的区域也包含许多神经元，这些神经元通过释放一种称为血清素的化学物质来相互交流。人们普遍认为这种化学物质可以产生幸福感。然而，目前尚不清楚这些特殊的“血清素能”神经元到底如何帮助处理奖励和惩罚。确定某种神经元在行为中所扮演的角色的理想方法是在行为执行时测量其电活动。然而，很难区分血清素能神经元的活动和周围非血清素能神经元的活动。为了克服这个问题，科恩等人。利用病毒迫使血清素能神经元形成一种离子通道，该通道可以响应光而产生电流。通过光纤照射这些神经元，然后测量神经元的反应，有助于制定标准，识别哪些反应是由血清素能神经元产生的。科恩等人。然后记录了口渴小鼠在经历一系列奖励（例如，一滴水）或惩罚（例如向眼睛吹一口空气）时血清素能神经元的活动。每次奖励或惩罚之前都会有一种独特的气味，这样老鼠就能学会预测即将发生的事情。这些实验表明，血清素能神经元通过改变其电活动的两个方面来对奖励和惩罚做出反应：产生短时的高活动爆发，以及改变其基线活动。一些血清素能神经元对惩罚做出快速反应，但对奖励则不然；当老鼠检测到即将给予奖励的气味时，其他人会迅速开火。小鼠接受的奖励或惩罚的平均水平也会影响许多血清素能神经元的基线活动。这种效果持续了几分钟。总的来说，科恩等人。表明血清素能神经元可以影响小鼠对短期和长期奖励或惩罚的反应。未来的实验应该旨在了解 Cohen 等人提出的信号的多样性。观察，并确定如何使用这些信号来驱动行为。最终，了解由不同类型细胞组成的神经回路如何工作可能有助于理解行为的神经基础。 DOI：http://dx.doi.org/10.7554/eLife.06346.002
Serotonin's function in the brain is unclear. One challenge in testing the numerous hypotheses about serotonin's function has been observing the activity of identified serotonergic neurons in animals engaged in behavioral tasks. We recorded the activity of dorsal raphe neurons while mice experienced a task in which rewards and punishments varied across blocks of trials. We ‘tagged’ serotonergic neurons with the light-sensitive protein channelrhodopsin-2 and identified them based on their responses to light. We found three main features of serotonergic neuron activity: (1) a large fraction of serotonergic neurons modulated their tonic firing rates over the course of minutes during reward vs punishment blocks; (2) most were phasically excited by punishments; and (3) a subset was phasically excited by reward-predicting cues. By contrast, dopaminergic neurons did not show firing rate changes across blocks of trials. These results suggest that serotonergic neurons signal information about reward and punishment on multiple timescales. DOI: http://dx.doi.org/10.7554/eLife.06346.001 Rewards and punishments can both encourage animals to change their immediate behavior and influence their mood over a longer term, particularly when given repeatedly. A region of the brain that increases its activity in response to rewards and punishments also contains many neurons that communicate with each other by releasing a chemical called serotonin. This chemical is commonly thought to produce feelings of happiness; however, it remains unclear exactly how these particular ‘serotonergic’ neurons help to process rewards and punishments. The ideal way to work out the role that a type of neuron plays in a behavior is to measure its electrical activity as the behavior is being performed. However, it is difficult to distinguish the activity of serotonergic neurons from the activity of the non-serotonergic neurons around them. To overcome this problem, Cohen et al. used viruses to force serotonergic neurons to make a type of ion channel that produces electrical currents in response to light. Shining light on these neurons via optical fibers and then measuring the neurons' responses helped to develop criteria that can identify which responses are generated by the serotonergic neurons. Cohen et al. then recorded the activity of serotonergic neurons in thirsty mice as they experienced a series of rewards (for example, a drop of water) or punishments (such as a puff of air to the eye). Each reward or punishment was preceded by a distinct odor, so that the mice learned to anticipate what was coming. These experiments revealed that serotonergic neurons respond to rewards and punishments by changing two aspects of their electrical activity: by producing short bursts of high activity, and by altering their baseline activity. Some of the serotonergic neurons fired rapidly in response to punishments, but not rewards; others fired rapidly when the mice detected a scent that meant that a reward was about to be given. The average level of reward or punishment the mice received also affected the baseline activity of many of the serotonergic neurons; this effect lasted for several minutes. Overall, Cohen et al. suggest that serotonergic neurons can affect how mice respond to rewards or punishments in both the short and long term. Future experiments should aim to understand the diversity of the signals that Cohen et al. observed, and to determine how these signals are used to drive behavior. Ultimately, understanding how neural circuits made up of different types of cells work may aid in understanding the neural basis of behavior. DOI: http://dx.doi.org/10.7554/eLife.06346.002