Today, we are launching a new blog series called MaxWell Monthly Must-Reads. Every month, we will feature interesting articles related to neuroscience, stem cell technology, drug discovery, and safety pharmacology. In this edition, we focus on Methods. We value well-designed experimental methods and protocols because they are key to new discoveries and ground-breaking results. Here, we include recent techniques for the generation of functionally active iPSC-derived neurons and brain organoids. We also feature a new single cell manipulation technique called virus stamping. In addition, we have MEA-related (MEA: microelectrode array) papers. One presenting a new open source package for MEA data analysis and another using our core technology for axonal action potential tracking.

  1. Reproducible and efficient generation of functionally active neurons from human hiPSCs for preclinical disease modeling
    by Yunyao Xie, Ryan J. Schutte, Nathan N. Ng, Kevin C. Ess, Philip H. Schwartz & Diane K. O’Dowd. Stem Cell Research. January 2018.

    This work presents efficient human induced pluripotent stem cell (hiPSC) differentiation protocols that allow generation of excitable neurons. Action potentials were observed as early as 4-5 days. Both glutamatergic and GABAergic neurons derived using the proposed methods were spontaneously active and formed network connections.

    Read the paper here.
  2. Cell diversity and network dynamics in photosensitive human brain organoids
    by Giorgia Quadrato, Tuan Nguyen, Evan Z. Macosko, John L. Sherwood, Sung Min Yang, Daniel R. Berger, Natalie Maria, Jorg Scholvin, Melissa Goldman, Justin P. Kinney, Edward S. Boyden, Jeff W. Lichtman, Ziv M. Williams, Steven A. McCarroll & Paola Arlotta. Nature. April 2017.

    3D in-vitro human brain models allow opportunities for in-depth investigation towards the understanding of the mechanisms involved during development and disease. This work analyzed the diversity of cells, formation of networks, and neuronal activity in human brain organoids.

    Read the paper here. More information can be found here.
  3. Virus stamping for targeted single-cell infection in vitro and in vivo
    by Rajib Schubert, Stuart Trenholm, Kamill Balint, Georg Kosche, Cameron S Cowan, Manuel A. Mohr, Martin Munz, David Martinez-Martin, Gotthold Fläschner, Richard Newton, Jacek Krol, Brigitte Gross Scherf, Keisuke Yonehara, Adrian Wertz, Aaron Ponti, Alexander Ghanem, Daniel Hillier, Karl-Klaus Conzelmann, Daniel J. Müller & Botond Roska. Nature Biotechnology. December 2017.

    Viral infection of single cells is a powerful technique to genetically engineer specific types of cells in the brain. This work describes a novel method called ‘virus stamping’, which utilizes magnetic nanoparticles inside a glass micropipette to deliver the virus to a target cell.

    Read the paper here. More information can be found here.
  4. meaRtools: an R package for the Comprehensive Analysis of Neuronal Networks Recorded on Multi-Electrode Arrays
    by Sahar Gelfman, Quanli Wang, Yi-Fan Lu, Diana Hall, Christopher Bostick, Ryan Dhindsa, Matt Halvorsen, K. Melodi McSweeney, Ellese Cotterill, Tom Edinburgh, Slave Petrovski, Michael J. Boland, Andrew S. Allen, David B. Goldstein & Stephen J. Eglen. Preprint in bioRxiv. January 2018.

    Microelectrode arrays (MEAs) are used to record the activity of hundreds to thousands of neurons connected in networks. This new R package called meaRtools can be used to analyze MEA recordings, with focus on features of the network such as burst synchronization, cross-correlation, mutual information, and many more.

    Read the paper here. Download the code from here.
  5. Tracking individual action potentials throughout mammalian axonal arbors
    by Milos Radivojevic, Felix Franke, Michael Altermatt, Jan Müller, Andreas Hierlemann & Douglas J. Bakkum. eLife. October 2017.

    Axons are very thin neuronal processes that send information (action potentials) to postsynaptic cells. Direct recording from axons is challenging, however this has been made easy using high-density microelectrode arrays (HD-MEAs) with very low noise. This work uses the core technology of MaxWell Biosystems to reveal single action potentials along axons (not averaged) and investigate the propagation of action potentials through individual axons and branch-points.

    Read the paper here.