Fluorescence imaging of large-scale neural ensemble dynamics

Cell, Journal Year: 2022, Volume and Issue: 185(1), P. 9 - 41

Published: Jan. 1, 2022

Language: Английский

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Structural basis for channel conduction in the pump-like channelrhodopsin ChRmine

Cell, Journal Year: 2022, Volume and Issue: 185(4), P. 672 - 689.e23

Published: Feb. 1, 2022

ChRmine, a recently discovered pump-like cation-conducting channelrhodopsin, exhibits puzzling properties (large photocurrents, red-shifted spectrum, and extreme light sensitivity) that have created new opportunities in optogenetics. ChRmine its homologs function as ion channels but, by primary sequence, more closely resemble pump rhodopsins; mechanisms for passive channel conduction this family remained mysterious. Here, we present the 2.0 Å resolution cryo-EM structure of revealing architectural features atypical channelrhodopsins: trimeric assembly, short transmembrane-helix 3, twisting extracellular-loop 1, large vestibules within monomer, an opening at trimer interface. We applied to design three proteins (rsChRmine hsChRmine, conferring further high-speed properties, respectively, frChRmine, combining faster performance) suitable fundamental neuroscience opportunities. These results illuminate gating channelrhodopsins point way toward structure-guided creation applications across biology.

Language: Английский

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All-optical physiology resolves a synaptic basis for behavioral timescale plasticity

Cell, Journal Year: 2023, Volume and Issue: 186(3), P. 543 - 559.e19

Published: Jan. 19, 2023

Learning has been associated with modifications of synaptic and circuit properties, but the precise changes storing information in mammals have remained largely unclear. We combined genetically targeted voltage imaging optogenetic activation silencing pre- post-synaptic neurons to study mechanisms underlying hippocampal behavioral timescale plasticity. In mice navigating a virtual-reality environment, individual CA1 cells at specific places induced stable representations these cells. Optical elicitation, recording, modulation transmission behaving revealed that activity presynaptic CA2/3 was required for induction plasticity and, furthermore, during place fields single cells, input from onto same potentiated. These results reveal implementation define methodology resolve learning memory mammals.

Language: Английский

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The logic of recurrent circuits in the primary visual cortex

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(1), P. 137 - 147

Published: Jan. 1, 2024

Abstract Recurrent cortical activity sculpts visual perception by refining, amplifying or suppressing input. However, the rules that govern influence of recurrent remain enigmatic. We used ensemble-specific two-photon optogenetics in mouse cortex to isolate impact from external found spatial arrangement and feature preference stimulated ensemble neighboring neurons jointly determine net effect activity. Photoactivation these ensembles drives suppression all cells beyond 30 µm but uniformly activation closer similarly tuned cells. In nonsimilarly cells, compact, cotuned drive suppression, while diffuse, activation. Computational modeling suggests highly local excitatory connectivity selective convergence onto inhibitory explain effects. Our findings reveal a straightforward logic which space their on

Language: Английский

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All-optical interrogation of neural circuits in behaving mice

Nature Protocols, Journal Year: 2022, Volume and Issue: 17(7), P. 1579 - 1620

Published: April 27, 2022

Language: Английский

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Ultrafast light targeting for high-throughput precise control of neuronal networks

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: April 5, 2023

Two-photon, single-cell resolution optogenetics based on holographic light-targeting approaches enables the generation of precise spatiotemporal neuronal activity patterns and thus a broad range experimental applications, such as high throughput connectivity mapping probing neural codes for perception. Yet, current limit tuning relative spiking time distinct cells to few milliseconds, achievable number targets 100-200, depending working depth. To overcome these limitations expand capabilities optogenetics, we introduce an ultra-fast sequential light targeting (FLiT) optical configuration rapid switching temporally focused beam between holograms at kHz rates. We used FLiT demonstrate two illumination protocols, termed hybrid- cyclic-illumination, achieve sub-millisecond control activation multicell in vitro (mouse organotypic acute brain slices) vivo (zebrafish larvae mice), while minimizing light-induced thermal rise. These will be important experiments that require cell stimulation with defined spatio-temporal large ensembles.

Language: Английский

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Holographic stimulation of opposing amygdala ensembles bidirectionally modulates valence-specific behavior via mutual inhibition

Neuron, Journal Year: 2023, Volume and Issue: 112(4), P. 593 - 610.e5

Published: Dec. 11, 2023

Language: Английский

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Optogenetic stimulation probes with single-neuron resolution based on organic LEDs monolithically integrated on CMOS

Nature Electronics, Journal Year: 2023, Volume and Issue: 6(9), P. 669 - 679

Published: Aug. 17, 2023

Abstract The use of optogenetic stimulation to evoke neuronal activity in targeted neural populations—enabled by opsins with fast kinetics, high sensitivity and cell-type subcellular specificity—is a powerful tool neuroscience. However, interface the opsins, deep-brain light delivery systems are required that match scale spatial temporal control offered molecular actuators. Here we show organic light-emitting diodes can be combined complementary metal–oxide–semiconductor technology create bright, actively multiplexed emissive elements. We implantable shanks which 1,024 individually addressable diode pixels 24.5 µm pitch integrated active drive circuitry. This integration is enabled controlled electrode conditioning, monolithic deposition optimized thin-film encapsulation. resulting probes used access brain regions as deep 5 mm selectively activate individual neurons millisecond-level precision mice.

Language: Английский

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Theoretical analysis of low-power deep synergistic sono-optogenetic excitation of neurons by co-expressing light-sensitive and mechano-sensitive ion-channels

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: March 6, 2025

The present challenge in neuroscience is to non-invasively exercise low-power and high-fidelity control of neurons situated deep inside the brain. Although, two-photon optogenetic excitation can activate millimeter depth with sub-cellular specificity millisecond temporal resolution, it also cause heating targeted tissue. On other hand, sonogenetics modulate cellular activity expressed mechano-sensitive proteins deeper areas brain less spatial selectivity. We a theoretical analysis synergistic sono-optogenetic method overcome these limitations by co-expressing (MscL-I92L) ion-channel light-sensitive (CoChR/ChroME2s/ChRmine) hippocampal neurons. It shown that presence low-amplitude subthreshold ultrasound pulses, threshold for neural spiking reduces drastically 73% MscL-I92L-CoChR (0.021 mW/µm2), 66% MscL-I92L-ChroME2s (0.029 64% MscL-I92L-ChRmine (0.013 mW/µm2) at 5 Hz. allows up 1.2 cm combination. useful design new experiments multimodal neuroprosthetic devices circuits.

Language: Английский

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Rhodopsins: An Excitingly Versatile Protein Species for Research, Development and Creative Engineering

Frontiers in Chemistry, Journal Year: 2022, Volume and Issue: 10

Published: June 22, 2022

The first member and eponym of the rhodopsin family was identified in 1930s as visual pigment rod photoreceptor cell animal retina. It found to be a membrane protein, owing its photosensitivity presence covalently bound chromophoric group. This group, derived from vitamin A, appropriately dubbed retinal. In 1970s microbial counterpart this species discovered an archaeon, being protein also harbouring retinal chromophore, named bacteriorhodopsin. Since their discovery photogenic panorama unfolded, where up date new members subspecies with variety light-driven functionality have been added family. branch, meanwhile categorized type-2 rhodopsins, turned out form large subclass superfamily G protein-coupled receptors are essential multiple elements light-dependent sensory physiology. type-1 largely function ion pumps or channels, but contain sensory-active enzyme-sustaining subspecies. review we will follow development exciting representative number highlights present prospect extraordinary future potential.

Language: Английский

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