Report of interval timing or action?
Report of interval timing or action?
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间隔时间或行动的报告？
DOI：
10.1073/pnas.1404555111
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发表时间：
2014
影响因子：
11.1
通讯作者：
HussainShuler,MarshallG
中科院分区：
文献类型：
--
作者：
Namboodiri,VijayMohanK;HussainShuler,MarshallG
Xu等人(1)认为内侧前额叶皮层（mPFC）参与了间隔计时。然而，我们认为他们的数据可以用mPFC简单地响应端口退出的假设来解释：指示定时间隔到期的动作。为了说明我们的论点，想象一下实验中增加了以下内容：当动物离开等待的端口时，向它们呈现一道闪光。假设初级视觉皮层（V1）中的神经元对光线做出反应，正如预期的那样。如果将这些反应与声音起始对齐绘制一个事件前后时间直方图（PETH）（如参考文献1的图3所示），V1中的神经元将显示出当光被传递时，出口周围的放电增加。重要的是，动物在离开并接受光线之前等待的时间将表现出一些可变性。由于计时行为遵循标量计时属性（2，3），因此间隔越长，此可变性将成比例地越大。当对试验中的PETH取平均值时，声-光间隔的变化将以缩放的方式影响PETH：变化更大的间隔对应于更温和的斜率。因此，在声音对齐PETH的神经反应的形式可以仅仅反映时间的分布，以一个急性视觉反应的声音，而不是一个斜坡的活动促进间隔时间。这个假设的结果与参考文献1中的图3相似，但人们是否会得出结论，V1中的神经元代表等待的时间间隔，而不是视觉刺激？参考文献1中的图2显示，所分析的神经元清楚地对端口出口做出响应。因此，mPFC神经元代表动物等待的时间间隔的结论有一个主要缺陷：神经反应可能仅仅传达了在端口中的状态，其反应的可扩展性来自于平均退出时间的缩放变化。为了在这个实验中展示间隔计时的神经实例，必须证明在出口没有计时的试验中，神经元对端口出口没有反应。这可以通过以下两种方式来完成：（i）要求动物在不同的提示后立即离开端口;以及（ii）在没有测试声音的情况下进行捕获试验，以便不能根据声音对退出进行计时。如果没有这些控制来排除出口相关的反应，最简单的解释是mPFC中的神经元只对端口出口做出反应。重要的是，Xu et al. s（1）的论文提供了一个大脑区域的操作，假设通过冷却mPFC来通知定时行为，并证明等待时间分布的右移。然而，由于PFC被认为是“根据内部目标协调思想和行动”（4），这在确定mPFC在计时中的作用方面也是不确定的，因为它可能（i）降低感知声音开始或存在于端口中的能力，（ii）减缓退出的决定，或类似地，（iii）减缓启动计时的决定，而在所有情况下都保持间隔计时本身不变。在没有这种控制的情况下，不可能确定冷却实验的结果是否真的是间隔时间受损的结果。
Xu et al.(1) argue that the medial prefrontal cortex (mPFC) is involved in interval timing. However, we believe that their data can be explained by the hypothesis that the mPFC simply responds to port exit: the action indicating the expiry of timed intervals. To illustrate our argument, imagine the following addition to the experiment: a flash of light is presented to animals when they exit the waiting port. Say that neurons in the primary visual cortex (V1) respond to the light, as expected. If one were to plot a peri-event time histogram (PETH) of these responses aligned to the sound onset (as in figure 3 of ref. 1), neurons in V1 would show an increase in firing around the exit, when the light is delivered. Importantly, the time waited by the animals until they exit and receive the light will exhibit some variability. Because timing behavior follows the scalar timing property (2, 3), this variability will be proportionally greater for longer intervals. When a PETH is averaged across trials, the variability in the sound-to-light interval will influence the PETH in a scaled fashion: a more variable interval corresponds to a gentler slope. The form of the neural response in the soundaligned PETH could therefore merely reflect the distribution of times to an acute visual response following the sound, not a ramping of activity facilitating interval timing. This hypothetical result is similar to figure 3 in ref. 1, yet would one conclude that neurons in V1 represent the interval waited and not the visual stimulus? Figure 2 in ref. 1 shows that the analyzed neurons clearly respond to the port exit. Hence, the conclusion that mPFC neurons represent the interval waited by animals has a major flaw: neural responses may merely convey the state of being in the port, with the scalability of their responses resulting from averaging scaled variability in exit times. To demonstrate a neural instantiation of interval timing in this experiment, it has to be shown that on trials in which the exit isn’t timed, neurons do not respond to the port exit. This may be done in the following two ways:(i) requiring animals to exit the port immediately after a different cue; and (ii) presenting catch trials without a test sound so that exits cannot be timed from the sound. Without these controls to rule out exit-related responses, the most parsimonious explanation is that neurons in the mPFC merely respond to the port exit. Importantly, Xu et al.’s (1) paper offers a manipulation of the brain region hypothesized to inform timed behavior by cooling mPFC and evidencing a right-shift in the distribution of wait-times. However, because the PFC is thought to “orchestrate thought and action in accordance with internal goals”(4), this too is indeterminate in establishing mPFC’s role in timing because it may (i) reduce the ability to sense the sound onset or presence in the port,(ii) slow the decision to exit, or similarly,(iii) slow the decision to initiate timing, while in all cases leaving interval timing—itself—intact. In the absence of such controls, it is impossible to ascertain whether the results of the cooling experiment are truly a result of impaired interval timing.
组织相容性抗原：结构和功能
DOI：
--
发表时间：
1982
期刊：
影响因子：
--
作者：
P. Parham;J. Strominger
通讯作者：
J. Strominger