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

Nature Methods, Год журнала: 2023, Номер 20(7), С. 1082 - 1094

Опубликована: Янв. 9, 2023

Язык: Английский

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Statistically unbiased prediction enables accurate denoising of voltage imaging data

Nature Methods, Год журнала: 2023, Номер 20(10), С. 1581 - 1592

Опубликована: Сен. 18, 2023

Abstract Here we report SUPPORT (statistically unbiased prediction utilizing spatiotemporal information in imaging data), a self-supervised learning method for removing Poisson–Gaussian noise voltage data. is based on the insight that pixel value data highly dependent its neighboring pixels, even when temporally adjacent frames alone do not provide useful statistical prediction. Such dependency captured and used by convolutional neural network with blind spot to accurately denoise which existence of action potential time frame cannot be inferred other frames. Through simulations experiments, show enables precise denoising types microscopy image while preserving underlying dynamics within scene.

Язык: Английский

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Photophysics-informed two-photon voltage imaging using FRET-opsin voltage indicators

Science Advances, Год журнала: 2025, Номер 11(2)

Опубликована: Янв. 8, 2025

Microbial rhodopsin–derived genetically encoded voltage indicators (GEVIs) are powerful tools for mapping bioelectrical dynamics in cell culture and live animals. Förster resonance energy transfer (FRET)–opsin GEVIs use voltage-dependent quenching of an attached fluorophore, achieving high brightness, speed, sensitivity. However, the sensitivity most FRET-opsin has been reported to decrease or vanish under two-photon (2P) excitation. Here, we investigated photophysics Voltron1 Voltron2. We found that previously negative-going sensitivities both came from photocycle intermediates, not opsin ground states. The were nonlinear functions illumination intensity; Voltron1, reversed sign low-intensity illumination. Using photocycle-optimized 2P protocols, demonstrate imaging with Voltron2 barrel cortex a mouse. These results open door high-speed vivo.

Язык: Английский

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Dendritic branch structure compartmentalizes voltage-dependent calcium influx in cortical layer 2/3 pyramidal cells

eLife, Год журнала: 2022, Номер 11

Опубликована: Март 23, 2022

Back-propagating action potentials (bAPs) regulate synaptic plasticity by evoking voltage-dependent calcium influx throughout dendrites. Attenuation of bAP amplitude in distal dendritic compartments alters a location-specific manner reducing bAP-dependent influx. However, it is not known if neurons exhibit branch-specific variability signals, independent distance-dependent attenuation. Here, we reveal that bAPs fail to evoke through voltage-gated channels (VGCCs) specific population branches mouse cortical layer 2/3 pyramidal cells, despite substantial VGCC-mediated sister branches. These contain VGCCs and successfully propagate the absence input; nevertheless, they bAP-evoked due reduction amplitude. We demonstrate these have more elaborate branch structure compared branches, which causes local electrotonic impedance Finally, show still amplify synaptically-mediated because differences voltage-dependence kinetics NMDA-type glutamate receptors. Branch-specific compartmentalization signals may provide mechanism for diversify tuning across tree.

Язык: Английский

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Synaptotagmin 7 sculpts short-term plasticity at a high probability synapse

Journal of Neuroscience, Год журнала: 2024, Номер unknown, С. e1756232023 - e1756232023

Опубликована: Янв. 23, 2024

Synapses with high release probability (

Язык: Английский

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Dendritic excitations govern back-propagation via a spike-rate accelerometer

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 4, 2025

Dendrites on neurons support electrical excitations, but the computational significance of these events is not well understood. We developed molecular, optical, and tools for all-optical electrophysiology in dendrites. mapped sub-millisecond voltage dynamics throughout dendritic trees CA1 pyramidal under diverse optogenetic synaptic stimulus patterns, acute brain slices. Our data show history-dependent spike back-propagation distal dendrites, driven by locally generated Na+ spikes (dSpikes). Dendritic depolarization created a transient window dSpike propagation, opened A-type KV channel inactivation, closed slow NaV inactivation. Collisions dSpikes with inputs triggered calcium N-methyl-D-aspartate receptor (NMDAR)-dependent plateau potentials accompanying complex at soma. This hierarchical ion network acts as spike-rate accelerometer, providing an intuitive picture connecting biophysics to associative plasticity rules. Neural mechanisms mediating information flow processing dendrites are fully Here authors techniques map bioelectrical excitations slices mouse tissue. They holistic roles back-propagation.

Язык: Английский

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Distinct synaptic plasticity rules operate across dendritic compartments in vivo during learning

Science, Год журнала: 2025, Номер 388(6744), С. 322 - 328

Опубликована: Апрель 17, 2025

Synaptic plasticity underlies learning by modifying specific synaptic inputs to reshape neural activity and behavior. However, the rules governing which synapses will undergo different forms of in vivo during whether these are uniform within individual neurons remain unclear. Using longitudinal imaging with single-synapse resolution mouse motor cortex learning, we found that apical basal dendrites layer 2/3 (L2/3) pyramidal showed distinct activity-dependent rules. The strengthening is predicted local coactivity nearby coincident postsynaptic action potentials, respectively. Blocking spiking diminished potentiation without affecting plasticity. Thus, use multiple a compartment-specific manner learning.

Язык: Английский

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Voltage dynamics of dendritic integration and back-propagationin vivo

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Май 26, 2023

Neurons integrate synaptic inputs within their dendrites and produce spiking outputs, which then propagate down the axon back into where they contribute to plasticity. Mapping voltage dynamics in dendritic arbors of live animals is crucial for understanding neuronal computation plasticity rules. Here we combine patterned channelrhodopsin activation with dual-plane structured illumination imaging, simultaneous perturbation monitoring somatic Layer 2/3 pyramidal neurons anesthetized awake mice. We examined integration compared optogenetically evoked, spontaneous, sensory-evoked back-propagating action potentials (bAPs). Our measurements revealed a broadly shared membrane throughout arbor, few signatures electrical compartmentalization among inputs. However, observed spike rate acceleration-dependent propagation bAPs distal dendrites. propose that this filtering may play critical role activity-dependent

Язык: Английский

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Dendritic excitations govern back-propagation via a spike-rate accelerometer

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Июнь 2, 2023

Dendrites on neurons support nonlinear electrical excitations, but the computational significance of these events is not well understood. We developed molecular, optical, and analytical tools to map sub-millisecond voltage dynamics throughout dendritic trees CA1 pyramidal under diverse optogenetic synaptic stimulus patterns, in acute brain slices. observed history-dependent spike back-propagation distal dendrites, driven by locally generated Na

Язык: Английский

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Assemblies, synapse clustering and network topology interact with plasticity to explain structure-function relationships of the cortical connectome

Опубликована: Ноя. 7, 2024

Synaptic plasticity underlies the brain’s ability to learn and adapt. While experiments in brain slices have revealed mechanisms protocols for induction of between pairs neurons, how these synaptic changes are coordinated biological neuronal networks ensure emergence learning remains poorly understood. Simulation modeling emerged as important tools study plastic networks, but yet achieve a scale that incorporates realistic network structure, active dendrites, multi-synapse interactions, key determinants plasticity. To rise this challenge, we endowed an existing large-scale cortical model, incorporating data-constrained dendritic processing multi-synaptic connections, with calcium-based model functional captures diversity excitatory connections extrapolated vivo -like conditions. This allowed us dendrites structure interact shape stimulus representations at microcircuit level. In our simulations, acted sparsely specifically, firing rates weight distributions remained stable without additional homeostatic mechanisms. At circuit level, found was driven by co-firing stimulus-evoked assemblies, spatial clustering synapses on topology connectivity. As result changes, became more reliable stimulus-specific responses. We confirmed testable predictions MICrONS datasets, openly available electron microscopic reconstruction large volume tissue. Our results quantify architecture higher-order microcircuits play central role provide foundation elucidating their learning.

Язык: Английский

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