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On the anniversary of the Boyden et al. (2005) paper that introduced the use of channelrhodopsin in neurons, Nature Neuroscience asks selected members of the community to comment on the utility, impact and future of this important technique.

Targeting genes to specific cell types is valuable for basic science and gene therapy. The authors describe a collection of AAVs containing synthetic promoters targeting a broad range of neuronal cell types in mice, non-human primates and humans.

Injured mouse retinal ganglion cells, upon a combination of treatments, can regrow their axons along the entire optic pathway and re-establish connections with their correct brain targets. This can partially restore function.

The authors monitored neuronal activity in mouse visual cortex during visual-motion stimulation and perturbed retinal direction selectivity. After perturbation, the proportion of posterior-motion-preferring cortical cells decreased, and their response at higher stimulus speeds was reduced. Thus, functionally distinct, retina-dependent and retina-independent computations of visual motion exist in mouse cortex.

Using several lines of retinal cell type–specific GENSET BAC transgenic GFP mice, the authors segregated these retinal cell types then subjected them to transcriptome microarray analysis to provide a transcriptional 'barcode' of retinal cell identity.

A base-editing approach optimized to target the retina shows high editing rates in a mouse model of Stargardt disease, as well as in nonhuman primates and ex vivo human retinal explants, paving the way for potential clinical applications.

Combined intraocular injection of an adeno-associated viral vector, encoding an optogenetic sensor, with light stimulation via engineered goggles enables partial recovery of visual function in a blind patient.

Pseudorabies viruses encoding fluorescent proteins are a powerful method for mapping neuronal circuits. Now a series of pseudorabies virus strains encoding fluorescent sensors and time-shifted florescent proteins allow dissection of complex circuits with concurrent activity analysis while defining an analysis period during which the neurons are still healthy.

The influence of sharp-wave ripples (SPW-Rs) on dendritic computation remains poorly understood. Here, the authors demonstrate the existence of SPW-R associated, branch-specific, dendritic spikes which serve as a temporal and spatial coincidence detectors during SPW-R-doublets in PV+ interneuron dendrites of awake mice.

Moculus is a virtual reality headset for mice that allows realistic display of three-dimensional environments. The system improves performance in visual-learning tasks and can be combined with various microscopes to study neural circuitry.

Viruses are transduced to single cells in tissues, organoids and in the mouse brain using mechanical carriers.

In vertebrate vision, the two types of photoreceptors, rods and cones, operate under low and bright light intensities, respectively. Here the authors show that under bright light conditions, when rods are not sensing light, they act as relay cells for cone-driven surround inhibition.

Using genetic labeling of cell types, two-photon microscopy, electrophysiology and theoretical modeling, the authors identify an approach-sensitive ganglion cell type in the mouse retina. They show that it is incorporated into a circuit that serves different purposes during daytime and night-time vision.

The strength and versatility of optogenetics rely not only on the diversity of the optogene toolkit but also on the ability to achieve spatially selective and temporally precise control of electrical activity in specific neural circuits, individual cells or subcellular compartments. This remains a challenge and requires sophisticated experimental designs. In this article, Packer, Roska and Häusser discuss the myriad combinations of optical, anatomical and genetic strategies that can be used to manipulate neuronal activity with light.

A multimodal atlas of retinal organoid development shows spatial interactions over time.

A Cre-dependent capsid selection method, CREATE, was used to produce adeno-associated viral vectors that allow gene delivery to the entire central and peripheral nervous systems, with multicolor labeling of single cells.

The mesoSPIM is an open hardware axially scanned light-sheet microscope for the rapid imaging of large cleared samples with isotropic resolution.

The mammalian retina is a modular brain region, in which cell layers are of uniform thickness but the molecular mechanism controlling this process is not well understood. Here the authors identify a regulatory network consisting of the long noncoding RNA Rncr4, RNA helicase Ddx3x and miR-183/96/182 that controls the even distribution of cells across layers.

Selective targeting of specific neuronal populations, for genetic or other manipulations, is crucial to much of neuroscience. The authors screened 536 BAC transgenic mouse lines from the GENSAT collection for specific reporter expression in the retina. Here, they describe several mouse lines selectively targeting different retinal cell types. The full dataset is accessible at http://www.gensat.org/retina.jsp.

In the retina, highly selective wiring from inhibitory cells contributes to determine the direction-selection characteristics of an individual ganglion cell, yet how the asymmetric wiring inherent to these connections is established was unknown. Here, two independent studies using complementary techniques, including pharmacology, electrophysiology and optogenetics, find that although inhibitory inputs to both sides of the direction-selective cell are uniform early in development, by the second postnatal week, inhibitory synapses on the null side strengthen whereas those on the preferred side remain constant. These plasticity changes occur independent of neural activity, indicating that a specific developmental program is executed to produce the direction-selective circuitry in the retina.

Sonogenetics provides neuron-specific activation at high spatiotemporal resolution ex vivo in retina and in vivo deep in the visual cortex using the AAV gene delivery of a mechanosensitive ion channel and low-intensity ultrasound stimulations.

The bed nucleus of the stria terminalis (BNST) is known to modulate anxiety-related behaviours. Here the authors show that excitatory inputs from infralimbic cortex and ventral subiculum/CA1 converge onto the same BNST neurons; stimulation of vSUB/CA1 triggers LTP in BNST and reduces anxiety in rats.

In epithelial layers cells must round up prior to division. Here the authors use micropillar arrays to mimic epithelial confinement and show that MDCK cells generate force to create space to divide; if unable to generate sufficient force they escape the micropillars to divide and return to confinement.

This protocol describes the targeted viral infection of single cells or small groups of cells by magnetically guided virus stamping, allowing for controlled genetic engineering, exemplified here by stamping cultured neurons with adeno-associated viruses.

An acousto-optic two-photon microscope with continuous three-dimensional trajectory and random-access scanning modes can scan near-cubic-millimeter volumes of tissue at sub-millisecond temporal resolution in vivo. The system can be used to image both sub-cellular as well as network-scale neuronal activity.

An atomic force microscope and confocal microscope set-up that allows nanomechanical mapping of virus binding under cell culture conditions shows that the first binding steps of a virus to a cell surface receptor are specific and weak, but affinity increases as more bonds are formed between the virus and cell surface receptors.

In this Technical Report, Chuong and colleagues introduce Jaws, an archaeon-derived, photoactivatable chloride pump that responds to red light. Owing to its efficiency in absorbing red photons and its large photocurrent, Jaws can be transcranially activated deep in the brain and thus allows noninvasive optogenetic silencing.

Cerebral blood volume dynamics in awake head-fixed mice are tracked via functional ultrasound imaging through a chronic cranial window, giving a high-resolution measure of brain-wide activity.