Photon Shot Noise Limits on Optical Detection of Neuronal Spikes and Estimation of Spike Timing

Abstract

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 Ca(2+) 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.

Genetically expressed voltage sensor ArcLight for imaging large scale cortical activity in the anesthetized and awake mouse

“…However, even these ratiometric approaches still require additional post hoc analysis to remove the properly scaled hemodynamic components from the recorded signals, which has been shown to be a nontrivial issue. 19,64 For the non-FRET-based imaging methodology of ArcLight, we found that the ongoing hemodynamic noise required additional post hoc processing through Off-ROI subtraction to gain access to single-trial responses in the S1 cortex of the anesthetized mouse.…”

Optical Strategies for Sensing Neuronal Voltage Using Quantum Dots and Other Semiconductor Nanocrystals

“…33 This will reduce the fidelity of spike detection since in the optical shotnoise-limited regime this fidelity scales as the square root of the fluorescence intensity. 34 In principle, the lower quantum yield value can be offset with higher excitation intensity.…”

“…35,36 To explore how well nanocrystals permit spike detection, we applied a recently developed theoretical framework that quantifies the capability to discriminate neural spikes optically in the regime of shotnoise-limited photon detection. 34 This framework allowed us to assess the contributions made to the spike detection fidelity by indicator attributes such as brightness, voltage sensitivity, and labeling density, as well as from the optical capabilities of the microscope, such as collection efficiency, frame rate, and excitation intensity. Our analysis helps guide experimental design and motivates rational improvements to nanocrystal indicators.…”

A method for improving wavelet threshold denoising in laser-induced breakdown spectroscopy

“…In the initial optical system, a fundamental noise source is photon shot noise, which results from the random nature of photon emission [25]. Photon shot noise is random, with a Poisson distribution of the number of detected photons [26]. Although some factors, such as the integration time and quantum efficiency of the detector, influence photon shot noise, its intrinsically random nature makes photon shot noise impossible to avoid.…”