Interferometric imaging of electrical signaling in biological cells

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Abstract/Contents

Abstract
Electrical signaling in biological cells is an important mediator of physiological functions, ranging from graded potentials in sensory neurons and other cells to action potentials in motor- and other neurons in the nervous system. The action potential constitutes the basic unit of neural information, and it is of particular interest to detect. Classically, this is done using invasive electrical measurements, such as a single-cell patch clamp or arrays of extracellular electrodes. More recent optical methods require exogenous markers, such as fluorescent calcium indicators, or genetically encoded transmembrane voltage sensors, and are thus still invasive. Truly non-invasive optical methods based on single-point laser interferometry have demonstrated nanometer-scale cellular deformations that accompany electrical events. This phenomenon can be exploited as an all-optical method for detection of action potentials and other electrical signaling. Here, I report full-field imaging of cellular deformations accompanying the action potential in mammalian neuron somas (-1.8 nm to 1.4 nm) and neurites (-0.7 nm to 0.9 nm), using high-speed common-path quantitative phase imaging with a temporal resolution of 0.1 ms and an optical path length sensitivity of < 4 pm per pixel. Spike-triggered averaging, synchronized to electrical recordings, demonstrates that the time course of the optical phase changes closely matches the dynamics of the electrical signal. Utilizing the spatial and temporal correlations of the phase signals across the cell, the detection and segmentation of spiking cells can be enhanced compared to the shot-noise limited performance of single pixels. These full-field observations of the spike-induced deformations shed light upon the electromechanical coupling mechanism in all electrogenic cells and open the door to non-invasive label-free imaging of neural signaling. Such electrically-induced cellular deformations can also be seen in photoreceptors during phototransduction in the human retina. Thus, wide-field label-free optical monitoring of neural activity using fast interferometry is an imminent diagnostic tool for noninvasive assessment of retinal function, and might find broader applications in neuroscience in general

Description

Type of resource text
Form electronic resource; remote; computer; online resource
Extent 1 online resource
Place California
Place [Stanford, California]
Publisher [Stanford University]
Copyright date 2020; ©2020
Publication date 2020; 2020
Issuance monographic
Language English

Creators/Contributors

Author Boyle, Kevin Conlon
Degree supervisor Palanker, Daniel
Thesis advisor Palanker, Daniel
Thesis advisor Solgaard, Olav
Thesis advisor Wetzstein, Gordon
Degree committee member Solgaard, Olav
Degree committee member Wetzstein, Gordon
Associated with Stanford University, Department of Electrical Engineering.

Subjects

Genre Theses
Genre Text

Bibliographic information

Statement of responsibility Kevin C. Boyle
Note Submitted to the Department of Electrical Engineering
Thesis Thesis Ph.D. Stanford University 2020
Location electronic resource

Access conditions

Copyright
© 2020 by Kevin Conlon Boyle
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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