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  1. Article ; Online: Spiking at the edge: Excitability at interfaces in reaction-diffusion systems.

    Scheibner, Colin / Ori, Hillel / Cohen, Adam E / Vitelli, Vincenzo

    Proceedings of the National Academy of Sciences of the United States of America

    2024  Volume 121, Issue 3, Page(s) e2307996120

    Abstract: Excitable media, ranging from bioelectric tissues and chemical oscillators to forest fires and competing populations, are nonlinear, spatially extended systems capable of spiking. Most investigations of excitable media consider situations where the ... ...

    Abstract Excitable media, ranging from bioelectric tissues and chemical oscillators to forest fires and competing populations, are nonlinear, spatially extended systems capable of spiking. Most investigations of excitable media consider situations where the amplifying and suppressing forces necessary for spiking coexist at every point in space. In this case, spikes arise due to local bistabilities, which require a fine-tuned ratio between local amplification and suppression strengths. But, in nature and engineered systems, these forces can be segregated in space, forming structures like interfaces and boundaries. Here, we show how boundaries can generate and protect spiking when the reacting components can spread out: Even arbitrarily weak diffusion can cause spiking at the edge between two non-excitable media. This edge spiking arises due to a global bistability, which can occur even if amplification and suppression strengths do not allow spiking when mixed. We analytically derive a spiking phase diagram that depends on two parameters: i) the ratio between the system size and the characteristic diffusive length-scale and ii) the ratio between the amplification and suppression strengths. Our analysis explains recent experimental observations of action potentials at the interface between two non-excitable bioelectric tissues. Beyond electrophysiology, we highlight how edge spiking emerges in predator-prey dynamics and in oscillating chemical reactions. Our findings provide a theoretical blueprint for a class of interfacial excitations in reaction-diffusion systems, with potential implications for spatially controlled chemical reactions, nonlinear waveguides and neuromorphic computation, as well as spiking instabilities, such as cardiac arrhythmias, that naturally occur in heterogeneous biological media.
    Language English
    Publishing date 2024-01-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2307996120
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Mapping uterine calcium dynamics during the ovulatory cycle in live mice.

    Combs, David J / Moult, Eric M / England, Sarah K / Cohen, Adam E

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Uterine contraction patterns vary during the ovulatory cycle and throughout pregnancy but prior measurements have produced limited and conflicting information on these patterns. We combined a virally delivered genetically encoded calcium reporter ( ... ...

    Abstract Uterine contraction patterns vary during the ovulatory cycle and throughout pregnancy but prior measurements have produced limited and conflicting information on these patterns. We combined a virally delivered genetically encoded calcium reporter (GCaMP8m) and ultra-widefield imaging in live nonpregnant mice to characterize uterine calcium dynamics at organ scale throughout the estrous cycle. Prior to ovulation (proestrus and estrus) uterine excitations primarily initiated in a region near the oviduct, but after ovulation (metestrus and diestrus), excitations initiated at loci homogeneously distributed throughout the organ. The frequency of excitation events was lowest in proestrus and estrus, higher in metestrus and highest in diestrus. These results establish a platform for mapping uterine activity, and show that the question of whether there is an anatomically localized trigger for uterine excitations depends on the estrous cycle phase.
    Language English
    Publishing date 2024-04-06
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.02.02.578395
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Photophysics-informed two-photon voltage imaging using FRET-opsin voltage indicators.

    Brooks, F Phil / Davis, Hunter C / Park, Pojeong / Qi, Yitong / Cohen, Adam E

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Microbial rhodopsin-derived genetically encoded voltage indicators (GEVIs) are powerful tools for mapping bioelectrical dynamics in cell culture and in live animals. Förster resonance energy transfer (FRET)-opsin GEVIs use voltage-dependent changes in ... ...

    Abstract Microbial rhodopsin-derived genetically encoded voltage indicators (GEVIs) are powerful tools for mapping bioelectrical dynamics in cell culture and in live animals. Förster resonance energy transfer (FRET)-opsin GEVIs use voltage-dependent changes in opsin absorption to modulate the fluorescence of an attached fluorophore, achieving high brightness, speed, and voltage sensitivity. However, the voltage sensitivity of most FRET-opsin GEVIs has been reported to decrease or vanish under two-photon (2P) excitation. Here we investigated the photophysics of the FRET-opsin GEVIs Voltron1 and 2. We found that the voltage sensitivity came from a photocycle intermediate, not from the opsin ground state. The voltage sensitivities of both GEVIs were nonlinear functions of illumination intensity; for Voltron1, the sensitivity reversed sign under low-intensity illumination. Using photocycle-optimized 2P illumination protocols, we demonstrate 2P voltage imaging with Voltron2 in barrel cortex of a live mouse. These results open the door to high-speed 2P voltage imaging of FRET-opsin GEVIs
    Language English
    Publishing date 2024-04-02
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.04.01.587540
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Membrane tension propagation couples axon growth and collateral branching.

    Shi, Zheng / Innes-Gold, Sarah / Cohen, Adam E

    Science advances

    2022  Volume 8, Issue 35, Page(s) eabo1297

    Abstract: Neuronal axons must navigate a mechanically heterogeneous environment to reach their targets, but the biophysical mechanisms coupling mechanosensation, growth, and branching are not fully understood. Here, we show that local changes in membrane tension ... ...

    Abstract Neuronal axons must navigate a mechanically heterogeneous environment to reach their targets, but the biophysical mechanisms coupling mechanosensation, growth, and branching are not fully understood. Here, we show that local changes in membrane tension propagate along axons at approximately 20 μm/s, more than 1000-fold faster than in most other nonmotile cells where this property has been measured. Local perturbations to tension decay along the axon with a length constant of approximately 41 μm. This rapid and long-range mechanical signaling mediates bidirectional competition between axonal branch initiation and growth cone extension. Our data suggest a mechanism by which mechanical cues at one part of a growing axon can affect growth dynamics remotely.
    Language English
    Publishing date 2022-08-31
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.abo1297
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Do Cell Membranes Flow Like Honey or Jiggle Like Jello?

    Cohen, Adam E / Shi, Zheng

    BioEssays. 2020 Jan., v. 42, no. 1

    2020  

    Abstract: Cell membranes experience frequent stretching and poking: from cytoskeletal elements, from osmotic imbalances, from fusion and budding of vesicles, and from forces from the outside. Are the ensuing changes in membrane tension localized near the site of ... ...

    Abstract Cell membranes experience frequent stretching and poking: from cytoskeletal elements, from osmotic imbalances, from fusion and budding of vesicles, and from forces from the outside. Are the ensuing changes in membrane tension localized near the site of perturbation, or do these changes propagate rapidly through the membrane to distant parts of the cell, perhaps as a mechanical mechanism of long‐range signaling? Literature statements on the timescale for membrane tension to equilibrate across a cell vary by a factor of ≈10⁶. This study reviews and discusses how apparently contradictory findings on tension propagation in cells can be evaluated in the context of 2D hydrodynamics and poroelasticity. Localization of tension in the cell membrane is likely critical in governing how membrane forces gate ion channels, set the subcellular distribution of vesicle fusion, and regulate the dynamics of cytoskeletal growth. Furthermore, in this study, it is proposed that cells can actively regulate the degree to which membrane tension propagates by modulating the density and arrangement of immobile transmembrane proteins. Also see the video abstract here https://youtu.be/T6K7AIAqqBs.
    Keywords cell membranes ; cytoskeleton ; hydrodynamics
    Language English
    Dates of publication 2020-01
    Publishing place John Wiley & Sons, Ltd
    Document type Article
    Note NAL-AP-2-clean ; JOURNAL ARTICLE
    ZDB-ID 50140-2
    ISSN 1521-1878 ; 0265-9247
    ISSN (online) 1521-1878
    ISSN 0265-9247
    DOI 10.1002/bies.201900142
    Database NAL-Catalogue (AGRICOLA)

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  6. Article ; Online: Optogenetics: Turning the Microscope on Its Head.

    Cohen, Adam E

    Biophysical journal

    2016  Volume 110, Issue 5, Page(s) 997–1003

    MeSH term(s) Animals ; Cells/metabolism ; Genes, Reporter ; Humans ; Luminescent Proteins/metabolism ; Microscopy/instrumentation ; Optogenetics/instrumentation ; Rhodopsin/metabolism
    Chemical Substances Luminescent Proteins ; Rhodopsin (9009-81-8)
    Language English
    Publishing date 2016-03-08
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 218078-9
    ISSN 1542-0086 ; 0006-3495
    ISSN (online) 1542-0086
    ISSN 0006-3495
    DOI 10.1016/j.bpj.2016.02.011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Optogenetic control of Nodal signaling patterns.

    McNamara, Harold M / Jia, Bill Z / Guyer, Alison / Parot, Vicente J / Dobbs, Caleb / Schier, Alexander F / Cohen, Adam E / Lord, Nathan D

    bioRxiv : the preprint server for biology

    2024  

    Abstract: A crucial step in early embryogenesis is the establishment of spatial patterns of signaling activity. Tools to perturb morphogen signals with high resolution in space and time can help reveal how embryonic cells decode these signals to make appropriate ... ...

    Abstract A crucial step in early embryogenesis is the establishment of spatial patterns of signaling activity. Tools to perturb morphogen signals with high resolution in space and time can help reveal how embryonic cells decode these signals to make appropriate fate decisions. Here, we present new optogenetic reagents and an experimental pipeline for creaHng designer Nodal signaling patterns in live zebrafish embryos. Nodal receptors were fused to the light-sensitive heterodimerizing pair Cry2/CIB1N, and the Type II receptor was sequestered to the cytosol. The improved optoNodal2 reagents eliminate dark activity and improve response kinetics, without sacrificing dynamic range. We adapted an ultra-widefield microscopy platform for parallel light patterning in up to 36 embryos and demonstrated precise spatial control over Nodal signaling activity and downstream gene expression. Patterned Nodal activation drove precisely controlled internalization of endodermal precursors. Further, we used patterned illumination to generate synthetic signaling patterns in Nodal signaling mutants, rescuing several characteristic developmental defects. This study establishes an experimental toolkit for systematic exploration of Nodal signaling patterns in live embryos.
    Language English
    Publishing date 2024-04-12
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.04.11.588875
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Do Cell Membranes Flow Like Honey or Jiggle Like Jello?

    Cohen, Adam E / Shi, Zheng

    BioEssays : news and reviews in molecular, cellular and developmental biology

    2019  Volume 42, Issue 1, Page(s) e1900142

    Abstract: Cell membranes experience frequent stretching and poking: from cytoskeletal elements, from osmotic imbalances, from fusion and budding of vesicles, and from forces from the outside. Are the ensuing changes in membrane tension localized near the site of ... ...

    Abstract Cell membranes experience frequent stretching and poking: from cytoskeletal elements, from osmotic imbalances, from fusion and budding of vesicles, and from forces from the outside. Are the ensuing changes in membrane tension localized near the site of perturbation, or do these changes propagate rapidly through the membrane to distant parts of the cell, perhaps as a mechanical mechanism of long-range signaling? Literature statements on the timescale for membrane tension to equilibrate across a cell vary by a factor of ≈10
    MeSH term(s) Cell Membrane/chemistry ; Cell Membrane/metabolism ; Cytoplasm/chemistry ; Cytoplasm/metabolism ; Diffusion ; Ion Channels/metabolism ; Membrane Proteins/metabolism ; Models, Biological
    Chemical Substances Ion Channels ; Membrane Proteins
    Language English
    Publishing date 2019-12-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 50140-2
    ISSN 1521-1878 ; 0265-9247
    ISSN (online) 1521-1878
    ISSN 0265-9247
    DOI 10.1002/bies.201900142
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Diminishing neuronal acidification by channelrhodopsins with low proton conduction.

    Hayward, Rebecca Frank / Brooks, F Phil / Yang, Shang / Gao, Shiqiang / Cohen, Adam E

    eLife

    2023  Volume 12

    Abstract: Many channelrhodopsins are permeable to protons. We found that in neurons, activation of a high-current channelrhodopsin, CheRiff, led to significant acidification, with faster acidification in the dendrites than in the soma. Experiments with patterned ... ...

    Abstract Many channelrhodopsins are permeable to protons. We found that in neurons, activation of a high-current channelrhodopsin, CheRiff, led to significant acidification, with faster acidification in the dendrites than in the soma. Experiments with patterned optogenetic stimulation in monolayers of HEK cells established that the acidification was due to proton transport through the opsin, rather than through other voltage-dependent channels. We identified and characterized two opsins which showed large photocurrents, but small proton permeability, PsCatCh2.0 and ChR2-3M. PsCatCh2.0 showed excellent response kinetics and was also spectrally compatible with simultaneous voltage imaging with QuasAr6a. Stimulation-evoked acidification is a possible source of disruptions to cell health in scientific and prospective therapeutic applications of optogenetics. Channelrhodopsins with low proton permeability are a promising strategy for avoiding these problems.
    MeSH term(s) Channelrhodopsins/genetics ; Protons ; Neurons ; Hydrogen-Ion Concentration ; Optogenetics
    Chemical Substances Channelrhodopsins ; Protons
    Language English
    Publishing date 2023-10-06
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.86833
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Optical constraints on two-photon voltage imaging.

    Davis, Hunter C / Brooks, F Phil / Wong-Campos, J David / Cohen, Adam E

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Genetically encoded voltage indicators (GEVIs) are a valuable tool for studying neural ... ...

    Abstract Genetically encoded voltage indicators (GEVIs) are a valuable tool for studying neural circuits
    Language English
    Publishing date 2023-11-18
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.11.18.567441
    Database MEDical Literature Analysis and Retrieval System OnLINE

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