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Journal ArticleDOI

Millisecond-timescale, genetically targeted optical control of neural activity.

TLDR
In this paper, the authors adapted the naturally occurring algal protein Channelrhodopsin-2, a rapidly gated light-sensitive cation channel, by using lentiviral gene delivery in combination with high-speed optical switching to photostimulate mammalian neurons.
Abstract
Temporally precise, noninvasive control of activity in well-defined neuronal populations is a long-sought goal of systems neuroscience. We adapted for this purpose the naturally occurring algal protein Channelrhodopsin-2, a rapidly gated light-sensitive cation channel, by using lentiviral gene delivery in combination with high-speed optical switching to photostimulate mammalian neurons. We demonstrate reliable, millisecond-timescale control of neuronal spiking, as well as control of excitatory and inhibitory synaptic transmission. This technology allows the use of light to alter neural processing at the level of single spikes and synaptic events, yielding a widely applicable tool for neuroscientists and biomedical engineers.

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A robust and high-throughput Cre reporting and characterization system for the whole mouse brain

TL;DR: A set of Cre reporter mice with strong, ubiquitous expression of fluorescent proteins of different spectra is generated and enables direct visualization of fine dendritic structures and axonal projections of the labeled neurons, which is useful in mapping neuronal circuitry, imaging and tracking specific cell populations in vivo.
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Driving fast-spiking cells induces gamma rhythm and controls sensory responses

TL;DR: The timing of a sensory input relative to a gamma cycle determined the amplitude and precision of evoked responses and provided the first causal evidence that distinct network activity states can be induced in vivo by cell-type-specific activation.
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Parvalbumin neurons and gamma rhythms enhance cortical circuit performance

TL;DR: Optogenetics opens the door to a new kind of informational analysis of brain function, permitting quantitative delineation of the functional significance of individual elements in the emergent operation and function of intact neural circuitry.
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Optogenetics in neural systems.

TL;DR: A primer on the application of optogenetics in neuroscience is provided, focusing on the single-component tools and highlighting important problems, challenges, and technical considerations.
Journal ArticleDOI

Independent optical excitation of distinct neural populations

TL;DR: Two channelrhodopsins, Chronos and Chrimson, are described, discovered through sequencing and physiological characterization of opsins from over 100 species of alga, that enable two-color activation of neural spiking and downstream synaptic transmission in independent neural populations without detectable cross-talk in mouse brain slice.
References
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Journal ArticleDOI

Synaptic Modifications in Cultured Hippocampal Neurons: Dependence on Spike Timing, Synaptic Strength, and Postsynaptic Cell Type

TL;DR: The results underscore the importance of precise spike timing, synaptic strength, and postsynaptic cell type in the activity-induced modification of central synapses and suggest that Hebb’s rule may need to incorporate a quantitative consideration of spike timing that reflects the narrow and asymmetric window for the induction of synaptic modification.
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A Third-Generation Lentivirus Vector with a Conditional Packaging System

TL;DR: It is demonstrated that the requirement for the tat gene can be offset by placing constitutive promoters upstream of the vector transcript, and the improved design presented here should facilitate testing of lentivirus vectors.
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Channelrhodopsin-2, a directly light-gated cation-selective membrane channel.

TL;DR: It is demonstrated by functional expression, both in oocytes of Xenopus laevis and mammalian cells, that ChR2 is a directly light-switched cation-selective ion channel, and may be used to depolarize small or large cells, simply by illumination.
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Reliability of spike timing in neocortical neurons

TL;DR: Data suggest a low intrinsic noise level in spike generation, which could allow cortical neurons to accurately transform synaptic input into spike sequences, supporting a possible role for spike timing in the processing of cortical information by the neocortex.
Journal ArticleDOI

Channelrhodopsin-1: a light-gated proton channel in green algae.

TL;DR: A complementary DNA sequence in the green alga Chlamydomonas reinhardtiithat encodes a microbial opsin-related protein, which is suggested to be Channelopsin-1, which shows homology to the light-activated proton pump bacteriorhodopsin.
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