Modeling pharmacological clock and memory patterns of interval timing in a striatal beat-frequency model with realistic, noisy neurons
Modeling pharmacological clock and memory patterns of interval timing in a striatal beat-frequency model with realistic, noisy neurons
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DOI：
10.3389/fnint.2011.00052
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发表时间：
2011-01-01
影响因子：
3.5
通讯作者：
Buhusi, Catalin V.
中科院分区：
文献类型：
--
作者：
Prise, Sorinel A.;Buhusi, Catalin V.
在大多数物种中，感知和使用秒到分钟范围内的时间流逝（间隔计时）的能力不仅是准确的，而且是标量的：时间估计的误差与估计的持续时间线性相关。标量计时的普遍性延伸到行为、病变和药理操作。例如，在哺乳动物中，多巴胺能药物引起感知时间（时钟模式）的立即标量变化，而胆碱能药物引起感知时间（记忆模式）逐渐的标量变化。这些特性是如何从不可靠、嘈杂的毫秒范围内放电的神经元中产生的？与间隔计时涉及的大脑回路相关的神经生物学信息为纹状体拍频（SBF）模型提供了支持，在该模型中，时间是通过皮层神经振荡器同时激活纹状体棘神经元来编码的。虽然在生物学上是合理的，但完美振荡器的不切实际或缺乏，对神经元嘈杂的大脑中的这种机制提出了质疑。我们探索了具有生物物理现实且嘈杂的 Morris-Lecar 神经元 (SBF-ML) 的 SBF 模型中时钟和记忆模式所需的计算机制。假设多巴胺能药物调节皮质振荡器的发射频率，并且胆碱能药物调节标准时间的记忆表示，我们表明我们的 SBF-ML 模型可以重现文献中观察到的药理学时钟和记忆模式。数值结果还表明，参数变异性（噪声）——以试验内和试验间神经振荡器固有频率的小波动以及记录/检索与标准时间相关的存储信息的错误的形式普遍存在——似乎对于时钟和记忆模式的时间尺度不变性至关重要。
In most species, the capability of perceiving and using the passage of time in the seconds-to-minutes range (interval timing) is not only accurate but also scalar: errors in time estimation are linearly related to the estimated duration. The ubiquity of scalar timing extends over behavioral, lesion, and pharmacological manipulations. For example, in mammals, dopaminergic drugs induce an immediate, scalar change in the perceived time (clock pattern), whereas cholinergic drugs induce a gradual, scalar change in perceived time (memory pattern). How do these properties emerge from unreliable, noisy neurons firing in the milliseconds range? Neurobiological information relative to the brain circuits involved in interval timing provide support for an striatal beat frequency (SBF) model, in which time is coded by the coincidental activation of striatal spiny neurons by cortical neural oscillators. While biologically plausible, the impracticality of perfect oscillators, or their lack thereof, questions this mechanism in a brain with noisy neurons. We explored the computational mechanisms required for the clock and memory patterns in an SBF model with biophysically realistic and noisy Morris-Lecar neurons (SBF-ML). Under the assumption that dopaminergic drugs modulate the firing frequency of cortical oscillators, and that cholinergic drugs modulate the memory representation of the criterion time, we show that our SBF-ML model can reproduce the pharmacological clock and memory patterns observed in the literature. Numerical results also indicate that parameter variability (noise) - which is ubiquitous in the form of small fluctuations in the intrinsic frequencies of neural oscillators within and between trials, and in the errors in recording/retrieving stored information related to criterion time - seems to be critical for the time-scale invariance of the clock and memory patterns.