Technical Reports

Elucidation of structure–function relationships in the nervous system necessitates biological circuit control with genetic and temporal precision. Here the authors engineer a genetically encoded magnetically sensitive actuator, “Magneto,” and remotely manipulate behavior in live zebrafish and mice. The magnetogenetic control over neural activity promises greater access to previously intractable tissues.

Recurrent, reciprocal genomic disorders due to non-allelic homologous recombination (NAHR) are a major cause of human disease. The authors developed a CRISPR/Cas9 genome engineering method that directly targets segmental duplications and efficiently mimics the NAHR-mediated mechanism of microdeletion and microduplication that occurs in vivo using 16p11.2 and 15q13.3 as proof-of-principle models.

The authors developed two subcellular optogenetic tools, pHoenix and lyso-pHoenix, that allow light-driven acidification of synaptic vesicles and lysosomes, respectively. pHoenix was used to control the degree of neurotransmitter uptake into synaptic vesicles, revealing that exocytosis of partially filled vesicles is less efficient than the release of completely filled vesicles.

A cortical parcellation technique accurately maps functional organization in individual brains. Functional networks mapped by this approach are highly reproducible and effectively capture individual variability. The algorithm performs well across different populations and data types and is validated by invasive cortical stimulation mapping in surgical patients.

ScaleS is a tissue clearing method for light and electron microscopy featuring stable tissue preservation for immunochemical and genetic labeling of tissue for 3D signal rendering. The technique enables quantitative and reproducible reconstructions of aged and diseased tissue in animal models and patients for high resolution optical pathology.

GFP reporter lines are useful for labeling specific cell types. Here, the authors developed a method to convert GFP expression directly into Cre recombinase activity. GFP-dependent Cre was delivered via electroporation or AAV to neural tissues in the mouse, and could be used for optogenetic control of specific cell types.

The authors developed a transcriptional reporter of intracellular Ca²⁺ and used it to monitor activity in Drosophila sensory and neuromodulatory neurons. They demonstrate that this tool can be used to manipulate neurons basis of their activity and report variants that can be adapted to report activity across a wide range.

In this technical report, Khodagholy and colleagues find that NeuroGrid, a planar, scalable and highly conformable electrode array, allows recordings of local-field potentials and stable single-unit activity from the surface of the rat cortex or hippocampus. The authors also validate NeuroGrid across species by showing that that it can capture LFP-modulated spiking activity intraoperatively in surgical patients, thus demonstrating its utility as tool for fundamental research on the human brain and in the clinic.

Lecoq and colleagues introduce a two-photon microscope with two articulated arms that can image nearly any two brain regions, nearby or distant, simultaneously. They validate this new system by imaging calcium signals in two visual cortical areas in behaving mice, and find evidence suggesting activity fluctuations can propagate between cortical areas

The authors report an optical method involving simultaneous stimulation of single neurons using a red-shifted optogenetic probe and recording of population activity using a green fluorescent calcium sensor. They use this technique to manipulate individual place cells in CA1 during spatial navigation in a virtual reality environment.

In this paper, Atasoy and colleagues use a genetically-encoded synaptic marker for electron microscopy (GESEM) to probe long-range neuronal connectivity at the nanoscale level. The authors fused the horseradish peroxidase to the vesicle-associated membrane protein 2 (VAMP2) to label synaptic vesicles. Focusing on the mouse feeding system, they show that this new tool is suitable for connectomics analyses of genetically defined populations of neurons.

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.

This Technical Report describes new methods of transcranial magnetic stimulation (TMS) in non-human primates. By combining single neuron recording with a modified TMS coil with focused stimulation in alert macaques, the authors show that this method can reduce stimulation artifact and allow investigation into the neuronal mechanisms of TMS.

In this technical report, St-Pierre and colleagues introduce a new genetically encoded voltage sensor called Accelerated Sensor of Action Potentials 1 (ASAP1), which consists of a circularly permuted GFP inserted in the extracellular voltage-sensing domain of a phosphatase. ASAP1 surpasses existing sensors in reliably detecting single action potentials and tracking subthreshold potentials and high-frequency spike trains.

In this Technical Report, the authors describe a new technique for the unambiguous lineage tracing of specific Drosophila neuroblasts. This methodology involves the use of lineage-restricted drivers and a modification to GAL4 expression such that it is now permanent and heritable to all descendant cells, directing reporter expression based on neuroblast identity rather than terminal neuronal characteristics.

In this Technical Report, the authors describe a new methodology for rapid and flexible knockdown of specific proteins in vitro and in vivo—without the need for genetic modification of the target—using a small peptide construct that targets the protein of interest and marks it for chaperone-mediated autophagy.

Existing noninvasive neuromodulation methods have poor spatial resolution and may affect neural activity in both the targeted cortical region and unintended surrounding networks. The authors demonstrate that transcranial focused ultrasound, a noninvasive technique with better spatial specificity, can alter neural activity within spatially confined regions of primary somatosensory cortex and enhance somatosensory discrimination.

In this technical report, the authors describe a new, red-shifted variant of channelrhodopsin (called red-activatable channelrhodopsin or ReaChR) that shows faster kinetics and greater photocurrents than currently available red-shifted probes. In addition, they show that ReaChR can be activated in awake mice through the intact skull.

This technical report describes a method to clear fixed brain tissues while allowing for fluorescent dye tracing and retaining cellular morphology. The authors demonstrate the utility of the technique by obtaining a wiring diagram for sister mitral cells.

This Technical Report describes light-activatable metabotropic glutamate receptors based on synthetic photoswitchable tethered ligands, and demonstrates optogenetic control of G protein–coupled receptor activity in neurons in vivo and ex vivo.