How neurons move during action potentials

Ling, Taotao; Boyle, Kevin C.; Zuckerman, Valentina; Flores, Thomas; Ramakrishnan, Charu; Deisseroth, Karl; Palanker, Daniel

doi:10.1101/765768

Cited by 5 publications

(10 citation statements)

References 55 publications

(65 reference statements)

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“…Rapid cellular deformations accompanying the changes in the transmembrane potential have been observed in multiple cell types, including the recent full-field interferometric imaging of HEK cells and neurons in culture [7]- [10], [14]. These measurements have established a linear relationship in typical cells between the membrane displacement and changes in cell potential, linked by the dependence of the membrane tension on transmembrane voltage.…”

Section: Voltage-dependent Membrane Tensionmentioning

confidence: 99%

“…To relate the observed mechanical deformations of cells to the underlying physiological processes, the coupling mechanisms must be known. Recently, we demonstrated that nm-scale deformations in neurons and other electrogenic cells can be explained by the voltage dependence of the membrane tension [8], [10]. Changes in the membrane tension necessarily cause a deformation to rebalance forces across the structure, whether it's a whole cell or an organelle.…”

Section: Introductionmentioning

confidence: 99%

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On mechanisms of light-induced deformations in photoreceptors

Boyle

Chen

Ling

et al. 2020

Preprint

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Photoreceptors in the retina convert light into electrical signals through a phototransduction cycle that consists of multiple electrical and biochemical events. Phase-resolved optical coherence tomography (pOCT) measurements of the optical path length (OPL) change in the cone photoreceptor outer segments after a light stimulus (optoretinogram) reveal a fast, ms-scale contraction by tens of nm, followed by a slow (hundreds of ms) elongation reaching hundreds of nm. Ultrafast measurements with a line-scan pOCT system show that the contractile response amplitude increases logarithmically with the number of incident photons, and its peak shifts earlier at higher stimulus intensities.We present a model that accounts for these features of the contractile response. Conformational changes in opsins after photoisomerization result in the fractional shift of charge across the disk membrane, leading to a transmembrane voltage change, known as the early receptor potential (ERP). Lateral repulsion of the ions on both sides of the membrane affects its surface tension and leads to its lateral expansion. Since the volume of the disks does not change much on a ms time scale, their lateral expansion leads to an axial contraction of the outer segment. With increasing stimulus intensity and resulting tension, the area expansion coefficient of the disk membrane also increases as thermally-induced fluctuations are pulled flat, resisting further expansion. This results in a logarithmic saturation of the deformation and a peak shift to earlier with brighter stimuli. Slow expansion of the photoreceptors is explained by the influx of water due to osmotic changes during phototransduction. Both effects closely match measurements in healthy human volunteers.

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Section: Voltage-dependent Membrane Tensionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

On mechanisms of light-induced deformations in photoreceptors

Boyle

Chen

Ling

et al. 2020

Preprint

Self Cite

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“…Quantitative phase imaging has been used to analyze diverse processes (9), such as, membrane mechanics, density of organelles, cell migration and more recently propagation of action potential (29). Polarized light imaging has enabled discovery of the dynamic microtubule spindle (5), assessment of structural integrity of meiotic spindles of oocytes in invitro fertilization (IVF) clinics (30), label-free imaging of white matter in adult human brain tissue slices (28,31), and imaging of activity-dependent structural changes in brain tissue (32).…”

Section: Introductionmentioning

confidence: 99%

Revealing architectural order with quantitative label-free imaging and deep learning

Guo

Krishnan

Folkesson

et al. 2019

Preprint

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Methods for imaging architecture of biological systems are currently not as scalable as genomic, transcriptomic, or proteomic technologies, because they rely on labels instead of intrinsic signatures. Label-free visualization of diverse biological structures is feasible with phase and polarization of light. However, distinguishing structures from information-dense label-free images is challenging. Recent advances in deep learning can distinguish structures from label-free images based on their shape. Here, we report joint use of polarization resolved imaging, reconstruction of optical properties, and deep neural networks for scalable analysis of complex structures. We reconstruct quantitative three-dimensional density, anisotropy, and orientation from polarization-and depthresolved images. We report a computationally efficient variant of U-Net architecture to predict 3D fluorescent structure from its density, anisotropy, and orientation. We evaluate the performance of our models by predicting anisotropic F-actin and isotropic nuclei. We report label-free prediction of myelination in human brain tissue sections and demonstrate the model's ability to rescue inconsistent labeling. We anticipate that the proposed approach will enable quantitative analysis of architectural order across scales of organelles to tissues. Label-free Microscopy | Polarization | Phase | Computational Imaging | Deep Learning Guo, Yeh, Folkesson et al. | bioRχiv | November 18, 2019 | 1-26 Guo, Yeh, Folkesson et al. | Learning architectural order bioRχiv | 3

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“…In general, the physiological processes associated with neural activity affect the cell's refractive index 4 and shape [5][6][7] , which together alter the light propagation, including changes in light scattering 8,9 , polarization 10 and optical path length (OPL) 5 . Similarly, cellular deformations accompanying the trans-membrane voltage change during the action potential have been documented in crustacean nerves 11,12 , squid giant axons 13 and mammalian neurons 7,14,15 . Interferometric imaging of such changes in general, and cellular deformations associated with variations in the cell potential, in particular, offers a non-invasive label-free optical approach to monitor the electrical activity in neurons 6 .…”

Section: Introductionmentioning

confidence: 99%

“…Using atomic force microscopy, Zhang et al demonstrated that HEK293 cells deformed proportionally to the membrane potential change (1 nm per 100 mV) 19 . Using quantitative phase microscopy, Ling et al demonstrated cellular deformations of up to 3 nm during the action potential in spiking HEK293 cells 6 , and about 1 nm in mammalian neurons 7 . Detecting the ms-fast and nm-scale cellular deformations in transmission is very challenging since the OPL difference between the cells and the surrounding medium scales with the refractive index difference, which is only ≈ 0.02.…”

Section: Introductionmentioning

confidence: 99%

The optoretinogram reveals how human photoreceptors deform in response to light

Kuchenbecker

et al. 2020

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Limited accessibility of retinal neurons to electrophysiology on a cellular scale in-vivo has restricted studies of their signaling to in-vitro preparations and animal models. Physiological changes underlying neural activity are mediated by variations in electrical potential that alter the surface tension of the cell membrane. In addition, physiological processes affect concentration of the cell's constituents that results in variation of osmotic pressure. Both these phenomena affect the neuron's shape which can be detected using interferometric imaging, thereby enabling non-invasive label-free imaging of physiological activity in-vivo with cellular resolution. Here, we apply high-speed phase-resolved optical coherence tomography in line-field configuration to image the biophysical phenomena associated with phototransduction in human cone photoreceptors in vivo. We demonstrate that individual cones exhibit a biphasic response to light: an early ms-scale fast contraction of the outer segment immediately after the onset of the flash stimulus followed by a gradual (hundreds of ms) expansion. We demonstrate that the contraction can be explained by rapid charge movement accompanying the isomerization of cone opsins, consistent with the early receptor potential observed in the electroretinogram and classical electrophysiology in-vitro. We demonstrate the fidelity of such all-optical recording of light-induced activity in the human retina, namely the optoretinogram, across a range of spatiotemporal scales. This approach incorporates functional evaluation into a routine clinical examination of retinal structure and thus holds enormous potential to serve as a biomarker for early disease diagnosis and monitoring therapeutic efficacy.

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How neurons move during action potentials

Cited by 5 publications

References 55 publications

On mechanisms of light-induced deformations in photoreceptors

On mechanisms of light-induced deformations in photoreceptors

Revealing architectural order with quantitative label-free imaging and deep learning

The optoretinogram reveals how human photoreceptors deform in response to light

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