Video-based pooled screening yields improved far-red genetically encoded voltage indicators

Tian, He; Davis, Hunter C.; Wong-Campos, J. D.; Park, Pojeong; Fan, Linlin Z.; Gmeiner, Björn; Begum, Shahinoor; Werley, Christopher A.; Borja, Gabriel B.; Upadhyay, Hansini; Shah, Himali; Jacques, Jane; Qi, Yitong; Parot, Vicente; Deisseroth, Karl; Cohen, Adam E.

doi:10.1038/s41592-022-01743-5

Cited by 44 publications

(29 citation statements)

References 66 publications

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“…We focused our investigation on the subclass of Archaerhodopsin-based GEVIs (QuasArs 16,24 and Archon 17 ) because of their low native quantum yield, and referred to Archon1 as a common template for their structure and function.…”

Section: Resultsmentioning

confidence: 99%

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Plasmonic Enhancement of Protein Function

Locarno,

Dong,

Meng

et al. 2024

Preprint

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The promise of voltage imaging using Genetically Encoded Voltage Indicators (GE-VIs) as a neuroscientific technique is hampered by GEVI limitations in brightness, response speed and sensitivity. Biochemical approaches like protein design and evolution are typically used to try and overcome these limitations, but suffer from the large number of possible proteins and mutations in the various GEVI families. Here we approach this problem in a physical way and report that plasmonic coupling to nanoparticles manipulates and enhances the photodynamics and fluorescence of GEVIs in live cells. We designed an optimal nanostar shape for plasmonic coupling through Finite-Difference Time-Domain (FDTD) computational models. We synthesized and characterized the resulting particles and quantified their influence on the brightness, voltage sensitivity, and response speed of the GEVI QuasAr6a. We incorporated the plasmonic enhancement into Markov chain photocycle models of Quasar6a, showing manipulation of both the light-dependent state transitions in the protein and of excited state fluorescence and paving the way for plasmonically enhanced voltage imaging.

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Section: Resultsmentioning

confidence: 99%

“…Typical efforts to create brighter GEVIs focus on biochemical approaches. 17–19 Many efforts have been made to engineer 20–22 or evolve 11,16,23,24 improved GEVIs. Additionally, protein FRET pairs have been used to enhance fluorescence brightness at the expense of voltage sensitivity.…”

Section: Introductionmentioning

confidence: 99%

Plasmonic Enhancement of Protein Function

Locarno,

Dong,

Meng

et al. 2024

Preprint

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“…Sncg is expressed selectively in CCKBCs; therefore, FlpO will be expressed specifically in this cell population in Sncg-FlpO mice. We expressed FlpO-dependent excitatory opsin (sombC1C2TG) ( 33 ) in CCKBCs and a soma-localized genetically encoded voltage indicator (GEVI, somQuasAr6a) ( 34 ) in sparsely labeled CA1 neurons in Sncg-FlpO mice (Fig. 3A and fig.…”

Section: Postsynaptic Activity–dependent Modulation Of Inhibitory Pos...mentioning

confidence: 99%

Retrograde endocannabinoid signaling at inhibitory synapses in vivo

Dudok,

Fan,

Farrell

et al. 2024

Science

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Endocannabinoid (eCB)–mediated suppression of inhibitory synapses has been hypothesized, but this has not yet been demonstrated to occur in vivo because of the difficulty in tracking eCB dynamics and synaptic plasticity during behavior. In mice navigating a linear track, we observed location-specific eCB signaling in hippocampal CA1 place cells, and this was detected both in the postsynaptic membrane and the presynaptic inhibitory axons. All-optical in vivo investigation of synaptic responses revealed that postsynaptic depolarization was followed by a suppression of inhibitory synaptic potentials. Furthermore, interneuron-specific cannabinoid receptor deletion altered place cell tuning. Therefore, rapid, postsynaptic, activity-dependent eCB signaling modulates inhibitory synapses on a timescale of seconds during behavior.

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“…[ 128,154 ] Video‐based screening of pooled libraries can be a powerful approach to target photoselection over a large field of view, enhancing the capabilities of imaging technologies. [ 163 ] A recent example involved the use of archaerhodopsin‐derived GEVIs to obtain live voltage imaging of mouse brains with improved signal‐to‐noise ratio (QuasAr6a) and kinetics (QuasAr6b). Such method may be translated to non‐excitable cells and tissues.…”

Section: Nanotechnologies For Cellular Electrophysiologymentioning

confidence: 99%

Nanotechnology and Cancer Bioelectricity: Bridging the Gap Between Biology and Translational Medicine

Moreddu

2023

Advanced Science

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Bioelectricity is the electrical activity that occurs within living cells and tissues. This activity is critical for regulating homeostatic cellular function and communication, and disruptions of the same can lead to a variety of conditions, including cancer. Cancer cells are known to exhibit abnormal electrical properties compared to their healthy counterparts, and this has driven researchers to investigate the potential of harnessing bioelectricity as a tool in cancer diagnosis, prognosis, and treatment. In parallel, bioelectricity represents one of the means to gain fundamental insights on how electrical signals and charges play a role in cancer insurgence, growth, and progression. This review provides a comprehensive analysis of the literature in this field, addressing the fundamentals of bioelectricity in single cancer cells, cancer cell cohorts, and cancerous tissues. The emerging role of bioelectricity in cancer proliferation and metastasis is introduced. Based on the acknowledgement that this biological information is still hard to access due to the existing gap between biological findings and translational medicine, the latest advancements in the field of nanotechnologies for cellular electrophysiology are examined, as well as the most recent developments in micro‐ and nano‐devices for cancer diagnostics and therapy targeting bioelectricity.

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Video-based pooled screening yields improved far-red genetically encoded voltage indicators

Cited by 44 publications

References 66 publications

Plasmonic Enhancement of Protein Function

Plasmonic Enhancement of Protein Function

Retrograde endocannabinoid signaling at inhibitory synapses in vivo

Nanotechnology and Cancer Bioelectricity: Bridging the Gap Between Biology and Translational Medicine

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