Photon Shot Noise Limits on Optical Detection of Neuronal Spikes and Estimation of Spike Timing
Photon Shot Noise Limits on Optical Detection of Neuronal Spikes and Estimation of Spike Timing
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DOI：
10.1016/j.bpj.2012.07.058
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发表时间：
2013-01-08
影响因子：
3.4
通讯作者：
Schnitzer, Mark J.
中科院分区：
文献类型：
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作者：
Wilt, Brian A.;Fitzgerald, James E.;Schnitzer, Mark J.
用于跟踪神经动力学的光学方法引起了广泛的兴趣，但一直缺乏量化这些技术的物理限制的理论框架。我们制定这样一个框架，通过使用信号检测和估计理论，以获得物理边界的检测神经尖峰和估计其发生时间的光子计数统计（散粒噪声）。这些界限通过取决于光学指示剂的动力学以及信号和背景光子的相对通量的可辨别性指数简洁地表示。这种方法有助于对不同指标、检测器技术和数据分析进行定量评估。我们的治疗还提供了最佳的过滤技术，用于尖峰的光学检测。我们比较了各种类型的Ca2+指标，并表明，背景光子是一个主要的障碍，电压感应。因此，响应于膜去极化而改变颜色的电压指示器可以提供优于改变强度的电压指示器的关键优势。我们还研究了荧光共振能量转移指标，并确定了广泛使用的比率信号分析的制度是基本上次优。总的来说，通过展示不同的光学因素如何相互作用以影响信号质量，我们的治疗为实验设计提供了有价值的指导，并提供了评估光学提取的神经活动痕迹的信心措施。
Optical approaches for tracking neural dynamics are of widespread interest, but a theoretical framework quantifying the physical limits of these techniques has been lacking. We formulate such a framework by using signal detection and estimation theory to obtain physical bounds on the detection of neural spikes and the estimation of their occurrence times as set by photon counting statistics (shot noise). These bounds are succinctly expressed via a discriminability index that depends on the kinetics of the optical indicator and the relative fluxes of signal and background photons. This approach facilitates quantitative evaluations of different indicators, detector technologies, and data analyses. Our treatment also provides optimal filtering techniques for optical detection of spikes. We compare various types of Ca2+ indicators and show that background photons are a chief impediment to voltage sensing. Thus, voltage indicators that change color in response to membrane depolarization may offer a key advantage over those that change intensity. We also examine fluorescence resonance energy transfer indicators and identify the regimes in which the widely used ratiometric analysis of signals is substantially suboptimal. Overall, by showing how different optical factors interact to affect signal quality, our treatment offers a valuable guide to experimental design and provides measures of confidence to assess optically extracted traces of neural activity.