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CaMPARI (Calcium Modulated Photoactivatable Ratiometric Integrator) – a fluorescent protein-based integrator of calcium for permanent marking of neuronal activity, Voltron – a chemigenetic fluorescent voltage indicator for in vivo recording of electrical activity. Primary use cases are marking/monitoring of neuronal activity in vivo in model organisms. Goal is to disseminate as broadly as possible, primarily via publicly-accessible repositories, to enable new biology.

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We have developed carbon fiber electrode arrays that can be optimized for either electrophsiology or the detection of dopamine. In addition, we have implemented tip sharpening techniques for better penetration into tissue such as nerves and ganglia. We wish to continue distributing these electrodes to existing collaborators and expand to new labs, with an overall emphasis on electrode customization per the user’s needs.

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Utilizing recent 3D nanoparticle printing advances, we provide exceptionally broad, dense ephys sampling across neural volumes. The CMU Array attains previously impossible densities (>6000 electrodes/cm2). More importantly, probes are fully-customizable. Any combination of positions, lengths, and impedances are possible. One-off probes are produced in hours, not weeks – and at a fraction of the cost. Even the probe platform is customizable –including curved and flexible substrates. We are currently exploring printed optogenetic waveguides and microfluidic drug delivery.

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We have developed (1) robotic platforms for automated cranial microsurgeries. (2) transparent polymer skulls for cortex-wide neural interfacing. (1) is currently being setup at multiple groups and we are helping these groups beta test. (2) is being shared via material transfer agreement to several groups at the NIH, Stanford, MIT, Johns Hopkins, UC Boulder and Princeton. We provide starter kits – with fully assembled implants, and raw materials for making dozens more. We hope to use STTR funds soon to be provided by the BRAIN Initiative to develop commercial versions of both.

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cytoNet provides a mathematical, web-based tool to rapidly characterize multiscale networks from images. To study complex tissue, cell and subcellular topologies, cytoNet integrates vision science with graph theory to quantify environmental effects on network topology. cytoNet applications include: (1) characterizing how pain sensation alters neural circuit activity in vivo, (2) quantifying patterns in how diverse brain cells respond to neurotrophic stimuli, & (3) uncovering cell cycle synchronization of differentiating neural stem cells. Awareness of cytoNet as a resource for the BRAIN Initiative community is a dissemination goal.

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We are developing genetically encoded indicators for monitoring voltage in vivo (GEVIs). Our tools can use the same wavelengths and equipment as used for imaging calcium indicators. We are open to new collaborators to deploy or benchmark these indicators for new applications, model systems, and/or imaging modalities.

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Magneto- and electro-encephalography (MEG/EEG) are the two methods to non-invasively record human brain activity with millisecond temporal resolution. MEG and EEG provide reliable markers of healthy brain function and disease states. However, the difficulty of relating these macroscopic signals to the underlying cellular- and circuit-level neural generators is a major, fundamental limitation that constrains using MEG/EEG to reveal novel principles of information processing or to translate the findings into new therapies for neural pathologies. To address this problem, we built the Human Neocortical Neurosolver (HNN, https://hnn.brown.edu). HNN is a user-friendly software tool designed to help researchers, and clinicians interpret the cellular and network origins of MEG/EEG data. HNN’s core is a detailed, mechanistic neural model including canonical features of a layered neocortical circuit, with layer-specific thalamocortical and cortico-cortical drive. HNN’s model is uniquely designed to account for the biophysical origin of the electrical currents generating MEG/EEG with enough detail to connect to the underlying cellular-level activity. HNN provides a user-friendly graphical user interface so that researchers can work interactively between model and data without needing to alter the underlying mathematical model or the open-source code. Tutorials on how to simulate the most commonly measured signals, including event related potentials and brain rhythms (alpha, beta, gamma), are provided. Researchers can compare simulated signals to recorded data and easily manipulate the model parameters to develop and test alternative hypotheses for the neural origin of their signals. Micro-scale features, including layer-specific responses, cell spiking activity, and somatic voltages, can be visualized and used to guide validation of model predictions with a variety of invasive and non-invasive methods. The ability of HNN to associate signals across scales makes it a unique tool for translational neuroscience research.

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We have developed micro-coil that can be implanted into the cortex and used to magnetically stimulate cortical neurons. Coils have two important advantages over conventional micro-electrodes. First, the magnetic fields they induce are less susceptible to changes in the surrounding environment, e.g. due to foreign body responses, and second, the fields they induce can be shaped to selectively target specific types of neurons.

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BARseq and MAPseq can map long-range projections of 1000s of neurons in a single brain area at single neuron resolution, and further correlate projections to gene expression and Cre. We achieve mapping of densely labeled neurons at single neuron resolution by cellular barcoding and sequencing. Our methods allow comparison of projections across neuronal subtypes within an animal, across individual animals, and across genotypes. We offer MAPseq service through CSHL core facility, and may offer BARseq service in the future. We also welcome other labs to adopt both methods on their own.

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Our goal is to disseminate high-density micro-LED optoelectrodes for mapping circuits in the brain.

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Miniature micro-endoscope. The micro-endoscope presented here has a small footprint, weight, and cost making it almost disposable. It can be used to record brain activity in multiple brain areas simultaneously in mice.

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Imaging deeper, wider, and faster. Imaging multiple species using multiphoton microscope. Dissemination through meetings, campus visits, and commercial vendors.

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Neuropixels are high-density, integrated probes for extracellular electrophysiology, available from neuropixels.org

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We have made and validated these nanoparticles (as supported by the BRAIN Initiative), and shown that after an intravenous infusion of the nanoparticles, they induce drug effects only when and where focused ultrasound is applied to the brain. We have seen that the particles may be loaded with any of a variety of neuromodulatory agents. We have also validated a production and storage scheme that will allow them to be stored long term and shipped frozen to collaborator sites. We are now working on a fool-proof protocol for any lab to easily make their own particles.

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The Open Ephys GUI is open-source, plugin-based cross-platform software for acquiring data from implanted electrodes, used by hundreds of labs around the world. It is available for download from open-ephys.org/gui

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We have built a set of open-source tools for precisely locking experimental perturbations (optical/electrical/magnetic stimulation, behavioral triggering, etc.) to the phase of ongoing LFP oscillations (probably could be used with anything that has an oscillation, e.g. whisking). They are substantially more accurate than anything in the published literature and have been adapted to work with both human and animal experimental rigs. The target use case is understanding the role of oscillatory phase in cognition, e.g. altering phase relations between structures by timed perturbation.

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We have developed a modular recordings system with soft, flexible polymer electrodes that makes it possible to record from hundreds of neurons distributed across many brain areas, and to do so for many months. We are currently distributing these electrodes to ~20 other labs for testing, and their feedback will be used to further refine the devices. Our long term goal is to be able to disseminate these devices to the entire community.

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We develop, validate, and enhance community access to a diverse toolbox of renewable recombinant antibodies and affinity reagents for neuroscience research. Extensively characterized in mammalian brain samples (rat, mouse, human).These reagents include conventional and recombinant mouse monoclonal antibodies and miniaturized ScFV derivatives, and nanobodies (single chain miniaturized antibodies). The small size, solubility, and stability of ScFvs and nAbs facilitates their functional expression in mammalian cells, allowing for their use as intrabodies to target cargo including optogenetic reports and actuators to distinct subcellular sites in neurons. Their small size also enhances the resolution of light and electron microscope imaging when they are used as immunolabels, and their penetration into intact cleared samples.

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single-cell combinatorial indexing on Microbiopsies Assigned to Positions for the Assay for Transposase Accessible Chromatin (sciMAP-ATAC). High-throughput single cell genomic assays resolve the heterogeneity of cell states in complex tissues, however, the spatial orientation within the network of interconnected cells is lost. We present a novel method for capturing spatially-resolved epigenomic profiles of single cells within intact tissue, and apply this method to generate non-neuronal cell taxonomy atlases of human and mouse cortex. This method will be made accessible through protocols.io and all data, along with single cell analyses, will be made available through the BRAIN Initiative Cell Census Network (BICCN)

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SLEAP (Social LEAP Estimates Animal Poses) is a deep learning software framework for general purpose multi-animal limb tracking from video. This software couples a GUI for importing and annotating data with deep neural networks designed for learning to locate and associate user-specified anatomical landmarks on unmarked animals. Use cases range from kinematic studies of animal movement, to quantification of social dynamics via multi-animal part tracking.

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I lead the development of the open source UCLA Miniscope project. We develop the most widely used miniature microscope for neural recording in freely behaving animals. Our system is currently in about 500 labs and we look to continue expanding access to transformative tools. New miniaturized microscopes: wireless, large field-of-view, integrated with electrophysiology. We disseminate our tools on miniscope.org

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The Floating Microelectrode Array allows stimulation and recording from the CNS and the periphery through a wireless link. This device is 5mm diameter and can interface to 16 electrodes without any wires or tethers. Power and communication is through a magnetic wireless link. The WFMA is being used for a clinical trial of cortical visual prosthesis, but has also been used for peripheral nerve (cuff) interface. Currently it is being deployed for neuroscience research through a joint effort by MicroProbes for Life Science and Sigenics, Inc.

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