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4 Janelia Publications

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    12/01/19 | Neuropixels data-acquisition system: A scalable platform for parallel recording of 10 000+ electrophysiological signals.
    Putzeys J, Musa S, Mora Lopez C, Raducanu BC, Carton A, De Ceulaer J, Karsh B, Siegle JH, Van Helleputte N, Harris TD, Dutta B
    IEEE Transactions on Biomedical Circuits and Systems. 2019 Dec 01;13(6):1635-1644. doi: 10.1109/TBCAS.2019.2943077

    Although CMOS fabrication has enabled a quick evolution in the design of high-density neural probes and neural-recording chips, the scaling and miniaturization of the complete data-acquisition systems has happened at a slower pace. This is mainly due to the complexity and the many requirements that change depending on the specific experimental settings. In essence, the fundamental challenge of a neural-recording system is getting the signals describing the largest possible set of neurons out of the brain and down to data storage for analysis. This requires a complete system optimization that considers the physical, electrical, thermal and signal-processing requirements, while accounting for available technology, manufacturing constraints and budget. Here we present a scalable and open-standards-based open-source data-acquisition system capable of recording from over 10,000 channels of raw neural data simultaneously. The components and their interfaces have been optimized to ensure robustness and minimum invasiveness in small-rodent electrophysiology.

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    09/25/19 | Can one concurrently record electrical spikes from every neuron in a mammalian brain?
    Kleinfeld D, Luan L, Mitra PP, Robinson JT, Sarpeshkar R, Shepard K, Xie C, Harris TD
    Neuron. 2019 Sep 25;103(6):1005. doi: 10.1016/j.neuron.2019.08.011

    The classic approach to measure the spiking response of neurons involves the use of metal electrodes to record extracellular potentials. Starting over 60 years ago with a single recording site, this technology now extends to ever larger numbers and densities of sites. We argue, based on the mechanical and electrical properties of existing materials, estimates of signal-to-noise ratios, assumptions regarding extracellular space in the brain, and estimates of heat generation by the electronic interface, that it should be possible to fabricate rigid electrodes to concurrently record from essentially every neuron in the cortical mantle. This will involve fabrication with existing yet nontraditional materials and procedures. We further emphasize the need to advance materials for improved flexible electrodes as an essential advance to record from neurons in brainstem and spinal cord in moving animals.

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    04/01/19 | Multimodal in vivo brain electrophysiology with integrated glass microelectrodes.
    Hunt DL, Lai C, Smith RD, Lee AK, Harris TD, Barbic M
    Nature Biomedical Engineering. 2019 Apr 01;3(9):741-53. doi: 10.1038/s41551-019-0373-8

    Electrophysiology is the most used approach for the collection of functional data in basic and translational neuroscience, but it is typically limited to either intracellular or extracellular recordings. The integration of multiple physiological modalities for the routine acquisition of multimodal data with microelectrodes could be useful for biomedical applications, yet this has been challenging owing to incompatibilities of fabrication methods. Here, we present a suite of glass pipettes with integrated microelectrodes for the simultaneous acquisition of multimodal intracellular and extracellular information in vivo, electrochemistry assessments, and optogenetic perturbations of neural activity. We used the integrated devices to acquire multimodal signals from the CA1 region of the hippocampus in mice and rats, and show that these data can serve as ground-truth validation for the performance of spike-sorting algorithms. The microdevices are applicable for basic and translational neurobiology, and for the development of next-generation brain-machine interfaces.

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    01/18/19 | Cortical column and whole-brain imaging with molecular contrast and nanoscale resolution.
    Gao R, Asano SM, Upadhyayula S, Pisarev I, Milkie DE, Liu T, Singh V, Graves AR, Huynh GH, Zhao Y, Bogovic JA, Colonell J, Ott CM, Zugates CT, Tappan S, Rodriguez A, Mosaliganti KR, Sheu S, Pasolli HA, et al
    Science (New York, N.Y.). 2019 Jan 18;363(6424):eaau8302. doi: 10.1126/science.aau8302

    Optical and electron microscopy have made tremendous inroads toward understanding the complexity of the brain. However, optical microscopy offers insufficient resolution to reveal subcellular details, and electron microscopy lacks the throughput and molecular contrast to visualize specific molecular constituents over millimeter-scale or larger dimensions. We combined expansion microscopy and lattice light-sheet microscopy to image the nanoscale spatial relationships between proteins across the thickness of the mouse cortex or the entire Drosophila brain. These included synaptic proteins at dendritic spines, myelination along axons, and presynaptic densities at dopaminergic neurons in every fly brain region. The technology should enable statistically rich, large-scale studies of neural development, sexual dimorphism, degree of stereotypy, and structural correlations to behavior or neural activity, all with molecular contrast.

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